The Official Patient's Sourcebook on Chronic Lymphocytic Leukemia: A Revised and Updated Directory for the Internet Age

THE OFFICIAL PATIENT’S SOURCEBOOK on CHRONIC LYMPHOCYTIC LEUKEMIA J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P...

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THE OFFICIAL PATIENT’S SOURCEBOOK

on

CHRONIC

LYMPHOCYTIC LEUKEMIA J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your physician. All matters regarding your health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The Official Patient’s Sourcebook on Chronic Lymphocytic Leukemia: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83460-1 1. Chronic Lymphocytic Leukemia-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of chronic lymphocytic leukemia.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to chronic lymphocytic leukemia. All of the Official Patient’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to chronic lymphocytic leukemia, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Adult Acute Lymphoblastic Leukemia

·

The Official Patient's Sourcebook on Adult Acute Myeloid Leukemia

·

The Official Patient's Sourcebook on Adult Hodgkin's Disease

·

The Official Patient's Sourcebook on Adult Non-hodgkin's Lymphoma

·

The Official Patient's Sourcebook on Chronic Lymphocytic Leukemia

·

The Official Patient's Sourcebook on Chronic Myelogenous Leukemia

·

The Official Patient's Sourcebook on Hairy Cell Leukemia

·

The Official Patient's Sourcebook on Hodgkin's Disease during Pregnancy

·

The Official Patient's Sourcebook on Multiple Myeloma and Other Plasma Cell Neoplasms

·

The Official Patient's Sourcebook on Mycosis Fungoides and the Sezary Syndrome

·

The Official Patient's Sourcebook on Myelodysplastic Syndromes

·

The Official Patient's Sourcebook on Myeloproliferative Disorders

·

The Official Patient's Sourcebook on Non-hodgkin's Lymphoma during Pregnancy

·

The Official Patient's Sourcebook on Primary Cns Lymphoma

To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

Contents vii

Table of Contents INTRODUCTION...................................................................................... 1

Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4

PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON CHRONIC LYMPHOCYTIC LEUKEMIA: GUIDELINES........................................................................ 9

Overview............................................................................................................... 9 What Is Chronic Lymphocytic Leukemia?.......................................................... 11 Stages of Chronic Lymphocytic Leukemia.......................................................... 12 How Is Chronic Lymphocytic Leukemia Treated? ............................................. 14 Treatment by Stage............................................................................................. 15 Stage 0 Chronic Lymphocytic Leukemia ............................................................ 16 To Learn More .................................................................................................... 18 About PDQ......................................................................................................... 20 More Guideline Sources ..................................................................................... 21 Vocabulary Builder............................................................................................. 23

CHAPTER 2. SEEKING GUIDANCE ....................................................... 27

Overview............................................................................................................. 27 Associations and Chronic Lymphocytic Leukemia ............................................. 27 Cancer Support Groups...................................................................................... 29 The Cancer Information Service ......................................................................... 31 Finding Cancer Resources in Your Community................................................ 34 Finding Doctors Who Specialize in Cancer Care ............................................... 37 Selecting Your Doctor ........................................................................................ 40 Working with Your Doctor ................................................................................ 41 Finding a Cancer Treatment Facility ................................................................. 42 Additional Cancer Support Information ............................................................ 44 Vocabulary Builder............................................................................................. 44

CHAPTER 3. CLINICAL TRIALS AND CHRONIC LYMPHOCYTIC LEUKEMIA ............................................................................................ 47

Overview............................................................................................................. 47 Recent Trials on Chronic Lymphocytic Leukemia.............................................. 50 Benefits and Risks............................................................................................... 83 Clinical Trials and Insurance Coverage ............................................................. 86 Clinical Trials and Medicare Coverage .............................................................. 89 Increasing the Likelihood of Insurance Coverage for Trials ............................... 90 If Your Insurance Claim Is Denied after the Trial Has Begun .......................... 92 Government Initiatives to Expand Insurance Coverage for Trials .................... 95

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Keeping Current on Clinical Trials.................................................................... 96 General References.............................................................................................. 97 Vocabulary Builder............................................................................................. 98

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL................................................ 101 CHAPTER 4. STUDIES ON CHRONIC LYMPHOCYTIC LEUKEMIA ....... 103

Overview........................................................................................................... 103 The Combined Health Information Database ................................................... 103 Federally Funded Research on Chronic Lymphocytic Leukemia...................... 105 E-Journals: PubMed Central ............................................................................ 118 The National Library of Medicine: PubMed .................................................... 120 Vocabulary Builder........................................................................................... 141

CHAPTER 5. PATENTS ON CHRONIC LYMPHOCYTIC LEUKEMIA ...... 149

Overview........................................................................................................... 149 Patents on Chronic Lymphocytic Leukemia ..................................................... 150 Patent Applications on Chronic Lymphocytic Leukemia ................................. 155 Keeping Current ............................................................................................... 155 Vocabulary Builder........................................................................................... 155

CHAPTER 6. BOOKS ON CHRONIC LYMPHOCYTIC LEUKEMIA ......... 157

Overview........................................................................................................... 157 The National Library of Medicine Book Index ................................................. 157 Chapters on Chronic Lymphocytic Leukemia................................................... 161 General Home References ................................................................................. 163 Vocabulary Builder........................................................................................... 164

CHAPTER 7. MULTIMEDIA ON CHRONIC LYMPHOCYTIC LEUKEMIA167 Overview........................................................................................................... 167 Bibliography: Multimedia on Chronic Lymphocytic Leukemia ....................... 167 Vocabulary Builder........................................................................................... 170

CHAPTER 8. PERIODICALS AND NEWS ON CHRONIC LYMPHOCYTIC LEUKEMIA .......................................................................................... 171

Overview........................................................................................................... 171 News Services & Press Releases ....................................................................... 171 Newsletters on Chronic Lymphocytic Leukemia .............................................. 175 Academic Periodicals Covering Chronic Lymphocytic Leukemia .................... 175 Vocabulary Builder........................................................................................... 179

CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 181

Overview........................................................................................................... 181 NIH Guidelines................................................................................................. 181 What Is Chronic Lymphocytic Leukemia?........................................................ 182 Stage Information ............................................................................................. 184 Rai Staging System .......................................................................................... 185 Binet Classification........................................................................................... 186

Contents

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Treatment Option Overview ............................................................................ 187 NIH Databases.................................................................................................. 199 Other Commercial Databases ........................................................................... 204 The Genome Project and Chronic Lymphocytic Leukemia............................... 204 Specialized References....................................................................................... 209 Vocabulary Builder........................................................................................... 210

CHAPTER 10. DISSERTATIONS ON CHRONIC LYMPHOCYTIC LEUKEMIA ........................................................................................................... 213

Overview........................................................................................................... 213 Dissertations on Chronic Lymphocytic Leukemia............................................ 213 Keeping Current ............................................................................................... 214

PART III. APPENDICES .................................................. 215 APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 217

Overview........................................................................................................... 217 Your Medications: The Basics .......................................................................... 218 Learning More about Your Medications .......................................................... 220 Commercial Databases...................................................................................... 221 Drug Development and Approval .................................................................... 222 Understanding the Approval Process for New Cancer Drugs......................... 224 The Role of the Federal Drug Administration (FDA)...................................... 224 Getting Drugs to Patients Who Need Them .................................................... 228 Contraindications and Interactions (Hidden Dangers) ................................... 230 A Final Warning .............................................................................................. 231 General References............................................................................................ 234 Vocabulary Builder........................................................................................... 235

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 237

Overview........................................................................................................... 237 What Is CAM? ................................................................................................. 238 What Are the Domains of Alternative Medicine?............................................ 239 Finding CAM References on Chronic Lymphocytic Leukemia ........................ 244 Additional Web Resources................................................................................ 255 General References............................................................................................ 255

APPENDIX C. FINDING MEDICAL LIBRARIES .................................... 259

Overview........................................................................................................... 259 Preparation ....................................................................................................... 259 Finding a Local Medical Library ...................................................................... 260 Medical Libraries Open to the Public............................................................... 260

APPENDIX D. YOUR RIGHTS AND INSURANCE ................................. 267

Overview........................................................................................................... 267 Your Rights as a Patient................................................................................... 267 Patient Responsibilities .................................................................................... 271 Choosing an Insurance Plan............................................................................. 272

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Contents

Medicare and Medicaid .................................................................................... 275 Financial Assistance for Cancer Care............................................................... 278 NORD’s Medication Assistance Programs ..................................................... 280 Additional Resources ........................................................................................ 281 Vocabulary Builder........................................................................................... 281

ONLINE GLOSSARIES.................................................... 283 Online Dictionary Directories.......................................................................... 287

CHRONIC LYMPHOCYTIC LEUKEMIA GLOSSARY ................................................................................................ 289 General Dictionaries and Glossaries ................................................................ 306

INDEX................................................................................... 308

Introduction

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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3

Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 Adapted from the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

2

Chronic Lymphocytic Leukemia

Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Chronic Lymphocytic Leukemia has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to chronic lymphocytic leukemia, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on chronic lymphocytic leukemia. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on chronic lymphocytic leukemia should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on

Introduction

3

appropriate options is always up to the patient in consultation with their physician and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching chronic lymphocytic leukemia (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to chronic lymphocytic leukemia. It also gives you sources of information that can help you find a doctor in your local area specializing in treating chronic lymphocytic leukemia. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with chronic lymphocytic leukemia. Part II moves on to advanced research dedicated to chronic lymphocytic leukemia. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on chronic lymphocytic leukemia. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with chronic lymphocytic leukemia or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with chronic lymphocytic leukemia. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with chronic lymphocytic leukemia.

Scope While this sourcebook covers chronic lymphocytic leukemia, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that chronic lymphocytic leukemia is often considered a synonym or a condition closely related to the following:

4

Chronic Lymphocytic Leukemia

·

Chronic Granulocytic Leukemia

·

Chronic Lymphocyte Leukemia

·

Chronic Myelocytic Leukemia

·

Chronic Myeloid Leukemia

·

Lymphocytic Leukemia

In addition to synonyms and related conditions, physicians may refer to chronic lymphocytic leukemia using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for chronic lymphocytic leukemia:4 ·

201.1 chronic myelogenous leukemia

·

204.1 leukemia, chronic lymphocytic

·

205.1 myeloid leukemia, chronic.

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to chronic lymphocytic leukemia. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for 4 This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

Introduction

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the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with chronic lymphocytic leukemia will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with chronic lymphocytic leukemia is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of chronic lymphocytic leukemia, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

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PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on chronic lymphocytic leukemia. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of chronic lymphocytic leukemia to you or even given you a pamphlet or brochure describing chronic lymphocytic leukemia. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

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CHAPTER 1. THE ESSENTIALS ON CHRONIC LYMPHOCYTIC LEUKEMIA: GUIDELINES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines on chronic lymphocytic leukemia. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on chronic lymphocytic leukemia can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased services that post them.

The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on chronic lymphocytic leukemia. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine. 5

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Chronic Lymphocytic Leukemia

There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with chronic lymphocytic leukemia and associated conditions: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Cancer Institute (NCI); guidelines available at http://cancernet.nci.nih.gov/pdq/pdq_treatment.shtml

Among the above, the National Cancer Institute (NCI) is particularly noteworthy. The NCI coordinates the National Cancer Program, which conducts and supports research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients.6 Specifically, the Institute: ·

Supports and coordinates research projects conducted by universities, hospitals, research foundations, and businesses throughout this country and abroad through research grants and cooperative agreements.

·

Conducts research in its own laboratories and clinics.

·

Supports education and training in fundamental sciences and clinical disciplines for participation in basic and clinical research programs and treatment programs relating to cancer through career awards, training grants, and fellowships.

·

Supports research projects in cancer control.

·

Supports a national network of cancer centers.

·

Collaborates with voluntary organizations and other national and foreign institutions engaged in cancer research and training activities.

·

Encourages and coordinates cancer research by industrial concerns where such concerns evidence a particular capability for programmatic research.

·

Collects and disseminates information on cancer.

This paragraph has been adapted from the NCI: http://www.nci.nih.gov/. “Adapted” signifies that a passage has been reproduced exactly or slightly edited for this book. 6

Guidelines 11

·

Supports construction of laboratories, clinics, and related facilities necessary for cancer research through the award of construction grants.

The NCI, established under the National Cancer Act of 1937, is the Federal Government’s principal agency for cancer research and training. The National Cancer Act of 1971 broadened the scope and responsibilities of the NCI and created the National Cancer Program. Over the years, legislative amendments have maintained the NCI authorities and responsibilities and added new information dissemination mandates as well as a requirement to assess the incorporation of state-of-the-art cancer treatments into clinical practice. Information dissemination is made possible through the NCI Online at www.cancer.gov. Cancer.gov offers to the public and physicians up-to-date information on the latest cancer research, current and upcoming clinical trials, statistics, research programs, and research funding. The following patient guideline was recently published by the NCI on chronic lymphocytic leukemia.

What Is Chronic Lymphocytic Leukemia?7 Chronic lymphocytic leukemia (CLL) is a disease in which too many infection-fighting white blood cells called lymphocytes are found in the body. Lymphocytes are made in the bone marrow and by other organs of the lymph system. The bone marrow is the spongy tissue inside the large bones in the body. The bone marrow makes red blood cells (which carry oxygen and other materials to all tissues of the body), white blood cells (which fight infection), and platelets (which make the blood clot). Normally, bone marrow cells called blasts develop (mature) into several different types of blood cells that have specific jobs to do in the body. The lymph system is made up of thin tubes that branch, like blood vessels, into all parts of the body. Lymph vessels carry lymph, a colorless, watery fluid that contains lymphocytes. Along the network of vessels are groups of small, bean-shaped organs called lymph nodes. Clusters of lymph nodes are found in the underarm, pelvis, neck, and abdomen. The spleen (an organ in the upper abdomen that makes lymphocytes and filters old blood cells from the blood), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat) are also part of the lymph system.

The following guidelines appeared on the NCI Web site on Aug. 26, 2002. The text was last modified in August 2002. The text has been adapted for this sourcebook. 7


Lymphocytes fight infection by making substances called antibodies, which attack germs and other harmful things in the body. In CLL, the developing lymphocytes do not mature correctly and too many are made. The lymphocytes may look normal, but they cannot fight infection as well as they should. These immature lymphocytes are then found in the blood and the bone marrow. They also collect in the lymph tissues and make them swell. Lymphocytes may crowd out other blood cells in the blood and bone marrow. Anemia may develop if the bone marrow cannot make enough red blood cells to carry oxygen. If the bone marrow cannot make enough platelets to make the blood clot normally, bleeding or bruising may occur easily. Leukemia can be acute (progressing quickly with many immature cells) or chronic (progressing slowly with more mature, normal-looking cells). Chronic lymphocytic leukemia progresses slowly and usually occurs in people 60 years of age or older. In the first stages of the disease there are often no symptoms. As time goes on, more and more lymphocytes are made and symptoms begin to appear. A doctor should be seen if the lymph nodes swell, the spleen or liver becomes larger than normal, a feeling of fatigue persists, or bleeding occurs easily. If there are symptoms, a doctor will do a physical examination and may order blood tests to count the number of each of the different kinds of blood cells. More blood tests may be done if the results of the blood tests are not normal. The doctor also may do a bone marrow biopsy. During this test, a needle is inserted into a bone and a small amount of bone marrow is taken out and looked at under the microscope. The doctor can then tell what kind of leukemia the patient has and plan the best treatment. The chance of recovery (prognosis) depends on the stage of the disease, and the patient’s age and general health.8

Stages of Chronic Lymphocytic Leukemia Once chronic lymphocytic leukemia has been found (diagnosed), more tests may be done to find out if leukemia cells have spread to other parts of the body. This is called staging. A doctor needs to know the stage of the disease

Refer to the PDQ summaries on Adult Acute Lymphocytic Leukemia Treatment; Childhood Acute Lymphocytic Leukemia Treatment; Adult Acute Myeloid Leukemia Treatment; Childhood Acute Myeloid Leukemia Treatment; Chronic Myelogenous Leukemia Treatment; and Hairy Cell Leukemia Treatment for more information. 8

Guidelines 13

to plan treatment. The following stages are used for chronic lymphocytic leukemia:

Stage 0 There are too many lymphocytes in the blood, but there are usually no other symptoms of leukemia. Lymph nodes and the spleen and liver are not swollen and the number of red blood cells and platelets is normal.

Stage I There are too many lymphocytes in the blood and lymph nodes are swollen. The spleen and liver are not swollen and the number of blood cells and platelets is normal. Stage II There are too many lymphocytes in the blood and lymph nodes and the liver and spleen are swollen.

Stage III There are too many lymphocytes in the blood and there are too few red blood cells (anemia). Lymph nodes and the liver or spleen may be swollen. Stage IV There are too many lymphocytes in the blood and too few platelets, which make it hard for the blood to clot. The lymph nodes, liver, or spleen may be swollen and there may be too few red blood cells (anemia).

Refractory Refractory means that the leukemia does not respond to treatment.


How Is Chronic Lymphocytic Leukemia Treated? There are treatments for all patients with chronic lymphocytic leukemia. Three kinds of treatment are used: ·

Chemotherapy (using drugs to kill cancer cells)

·

Radiation therapy (using high-dose x-rays or other high-energy rays to kill cancer cells)

·

Treatment for complications of the leukemia, such as infection.

The use of biological therapy (using the body’s immune system to fight cancer) is being tested in clinical trials. Surgery may be used in certain cases. Chemotherapy Chemotherapy uses drugs to kill cancer cells. Chemotherapy may be taken by pill, or it may be put into the body by a needle in the vein or muscle. Chemotherapy is called a systemic treatment because the drug enters the bloodstream, travels through the body, and can kill cancer cells throughout the body.

Radiation Therapy Radiation therapy uses x-rays or other high-energy rays to kill cancer cells and shrink tumors. Radiation for CLL usually comes from a machine outside the body (external radiation therapy). Treatment for Complications If the spleen is swollen, a doctor may take out the spleen in an operation called a splenectomy. This is only done in rare cases.

Guidelines 15

Biological Therapy Biological therapy tries to get the body to fight cancer. It uses materials made by the body or made in a laboratory to boost, direct, or restore the body’s natural defenses against disease. Biological therapy is sometimes called biological response modifier (BRM) therapy or immunotherapy. ·

Because infection often occurs in patients with CLL, a special substance called immunoglobulin, which contains antibodies, may be given to prevent infections.

·

Sometimes a special machine is used to filter the blood to take out extra lymphocytes. This is called leukapheresis.

Bone Marrow Transplantation Bone marrow transplantation is used to replace the bone marrow with healthy bone marrow. First, all of the bone marrow in the body is destroyed with high doses of chemotherapy with or without radiation therapy. Healthy marrow is then taken from another person (a donor) whose tissue is the same as or almost the same as the patient’s. The donor may be a twin (the best match), a brother or sister, or another person not related. The healthy marrow from the donor is given to the patient through a needle in the vein, and the marrow replaces the marrow that was destroyed. A bone marrow transplant using marrow from a relative or person not related to the patient is called an allogeneic bone marrow transplant. Another type of bone marrow transplant, called autologous bone marrow transplant, is being studied in clinical trials. To do this type of transplant, bone marrow is taken from the patient and treated with drugs to kill any cancer cells. The marrow is frozen to save it. Next, the patient is given highdose chemotherapy with or without radiation therapy to destroy all of the remaining marrow. The frozen marrow that was saved is then thawed and given back to the patient through a needle in a vein to replace the marrow that was destroyed.

Treatment by Stage Treatment of chronic lymphocytic leukemia depends on the stage of the disease, and the patient’s age and overall health.


Standard treatment may be considered because of its effectiveness in patients in past studies, or participation in a clinical trial may be considered. Most patients with chronic lymphocytic leukemia are not cured with standard therapy and some standard treatments may have more side effects than are desired. For these reasons, clinical trials are designed to find better ways to treat cancer patients and are based on the most up-to-date information. Clinical trials are on going in most parts of the country for most stages of chronic lymphocytic leukemia. To know more about clinical trials, call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237); TTY at 1800-332-8615.

Stage 0 Chronic Lymphocytic Leukemia If the patient has stage 0 CLL, treatment may not be needed or chemotherapy may be given. A doctor will follow the patient closely so treatment can be started if the leukemia gets worse.

Stage I Chronic Lymphocytic Leukemia Treatment may be one of the following: ·

If there are no symptoms, no treatment may be needed. A doctor will follow the patient closely so treatment can be started if the leukemia gets worse.

·

Chemotherapy with or without steroids.

·

Other chemotherapy drugs.

·

External radiation therapy to swollen lymph nodes.

·

Combination chemotherapy.

·

A clinical trial evaluating monoclonal antibodies.

·

A clinical trial evaluating bone marrow or peripheral stem cell transplantation.

Guidelines 17

Stage II Chronic Lymphocytic Leukemia Treatment may be one of the following: ·

If there are few or no symptoms, no treatment may be needed. A doctor will follow the patient closely so treatment can be started if the leukemia gets worse.

·


·


·


·

External radiation therapy to swollen lymph nodes.

·

External radiation therapy to the spleen to reduce symptoms caused by the enlargement of the spleen.

·


·


Stage III Chronic Lymphocytic Leukemia Treatment may be one of the following: ·


·


·


·


·

Surgery to remove the spleen or external radiation therapy to the spleen to reduce symptoms caused by the enlargement of the spleen.

·


·



Stage IV Chronic Lymphocytic Leukemia Treatment may be one of the following: ·


·


·


·


·

Surgery to remove the spleen or external radiation therapy to the spleen to reduce symptoms caused by the enlargement of the spleen.

·


·


Refractory Chronic Lymphocytic Leukemia Treatment depends on many factors; patients may wish to consider entering a clinical trial of new chemotherapy drugs and bone marrow or peripheral stem cell transplantation.

To Learn More Call For more information, U.S. residents may call the National Cancer Institute’s (NCI’s) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-4226237), Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-ofhearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.

Web Sites and Organizations The NCI’s Cancer.gov Web site (http://cancer.gov) provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. There

Guidelines 19

are also many other places where people can get materials and information about cancer treatment and services. Local hospitals may have information on local and regional agencies that offer information about finances, getting to and from treatment, receiving care at home, and dealing with problems associated with cancer treatment. Publications The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator (https://cissecure.nci.nih.gov/ncipubs). These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-8004-CANCER (1-800-422-6237), TTY at 1-800-332-8615. LiveHelp The NCI’s LiveHelp service, a program available on several of the Institute’s Web sites, provides Internet users with the ability to chat online with an Information Specialist. The service is available from Monday - Friday 9:00 AM - 10:00 PM Eastern Time. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer. Write For more information from the NCI, please write to this address: National Cancer Institute Office of Communications 31 Center Drive, MSC 2580 Bethesda, MD 20892-2580


About PDQ PDQ Is a Comprehensive Cancer Database Available on Cancer.gov PDQ is the National Cancer Institute’s (NCI’s) comprehensive cancer information database. Most of the information contained in PDQ is available online at Cancer.gov (http://cancer.gov), the NCI’s Web site. PDQ is provided as a service of the NCI. The NCI is part of the National Institutes of Health, the federal government’s focal point for biomedical research.

PDQ Contains Cancer Information Summaries The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries are available in two versions. The health professional versions provide detailed information written in technical language. The patient versions are written in easy-tounderstand, non-technical language. Both versions provide current and accurate cancer information. The PDQ cancer information summaries are developed by cancer experts and reviewed regularly. Editorial Boards made up of experts in oncology and related specialties are responsible for writing and maintaining the cancer information summaries. The summaries are reviewed regularly and changes are made as new information becomes available. The date on each summary (“Date Last Modified”) indicates the time of the most recent change.

PDQ Contains Information on Clinical Trials Before starting treatment, patients may want to think about taking part in a clinical trial. A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about new treatments, the risks involved, and how well they do or do not work. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become “standard.” Listings of clinical trials are included in PDQ and are available online at Cancer.gov (http://cancer.gov/clinical_trials). Descriptions of the trials are

Guidelines 21

available in health professional and patient versions. Many cancer doctors who take part in clinical trials are also listed in PDQ. For more information, call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237); TTY at 1-800-332-8615.

More Guideline Sources The guideline above on chronic lymphocytic leukemia is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to chronic lymphocytic leukemia. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with chronic lymphocytic leukemia. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.


The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “chronic lymphocytic leukemia” or synonyms. The following was recently posted: ·

An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia. Source: American Society of Hematology.; 1999 September 1; 20 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1589&sSearch_string=chronic+myelogenous+leukemia

·

Drug therapy for chronic myeloid leukemia. Source: Cancer Care Ontario Practice Guidelines Initiative.; 1998 August 24 (updated online 2000 Jul); Various pagings http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2231&sSearch_string=chronic+myelogenous+leukemia Healthfinder™

Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to chronic lymphocytic leukemia. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful

Guidelines 23

background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

·

drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

·

Family Village: http://www.familyvillage.wisc.edu/specific.htm

·

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

·

Med Help International: http://www.medhelp.org/HealthTopics/A.html

·

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

·

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

·

WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Abdomen: The part of the body that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Anemia: A condition in which the number of red blood cells is below normal. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Biopsy: The removal of cells or tissues for examination under a microscope. When only a sample of tissue is removed, the procedure is called an incisional biopsy or core biopsy. When an entire tumor or lesion is removed,


the procedure is called an excisional biopsy. When a sample of tissue or fluid is removed with a needle, the procedure is called a needle biopsy or fineneedle aspiration. [NIH] Blasts: Immature blood cells. [NIH] Busulfan: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents, characterized in the acute stage by erythema, edema associated with a serous exudate between the cells of the epidermis (spongiosis) and an inflammatory infiltrate in the dermis, oozing and vesiculation, and crusting and scaling; and in the more chronic stages by lichenification or thickening or both, signs of excoriations, and hyperpigmentation or hypopigmentation or both. Atopic dermatitis is the most common type of dermatitis. Called also eczematous dermatitis. [EU] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hydroxyurea: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunotherapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also called biological therapy or biological response modifier (BRM) therapy. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Intestinal: Having to do with the intestines. [NIH]

Guidelines 25

Leukapheresis: Removal of the blood to collect specific blood cells; the remaining blood is returned to the body. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Oncology: The study of cancer. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Refractory: Not readily yielding to treatment. [EU] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Systemic: Affecting the entire body. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Tonsils: Small masses of lymphoid tissue on either side of the throat. [NIH] Transplantation: person. [NIH]

The replacement of an organ with one from another

Seeking Guidance 27

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with chronic lymphocytic leukemia. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.9 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with chronic lymphocytic leukemia. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Chronic Lymphocytic Leukemia As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.10 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 10 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 9


influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information, by consulting all of them, you will have nearly exhausted all sources for patient associations.

The National Cancer Institute (NCI) The National Cancer Institute (NCI) has complied a list of national organizations that offer services to people with cancer and their families. To view the list, see the NCI fact sheet online at the following Web address: http://cis.nci.nih.gov/fact/8_1.htm. The name of each organization is accompanied by its contact information and a brief explanation of its services.

The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about chronic lymphocytic leukemia. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “chronic lymphocytic leukemia” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

Seeking Guidance 29

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “chronic lymphocytic leukemia”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “chronic lymphocytic leukemia” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with chronic lymphocytic leukemia. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “chronic lymphocytic leukemia” (or a synonym) in the search box.

Cancer Support Groups11 People diagnosed with cancer and their families face many challenges that may leave them feeling overwhelmed, afraid, and alone. It can be difficult to cope with these challenges or to talk to even the most supportive family members and friends. Often, support groups can help people affected by cancer feel less alone and can improve their ability to deal with the uncertainties and challenges that cancer brings. Support groups give people who are affected by similar diseases an opportunity to meet and discuss ways to cope with the illness.

11

This section has been adapted from the NCI: http://cis.nci.nih.gov/fact/8_8.htm.


How Can Support Groups Help? People who have been diagnosed with cancer sometimes find they need assistance coping with the emotional as well as the practical aspects of their disease. In fact, attention to the emotional burden of cancer is sometimes part of a patient’s treatment plan. Cancer support groups are designed to provide a confidential atmosphere where cancer patients or cancer survivors can discuss the challenges that accompany the illness with others who may have experienced the same challenges. For example, people gather to discuss the emotional needs created by cancer, to exchange information about their disease—including practical problems such as managing side effects or returning to work after treatment—and to share their feelings. Support groups have helped thousands of people cope with these and similar situations. Can Family Members and Friends Participate in Support Groups? Family and friends are affected when cancer touches someone they love, and they may need help in dealing with stresses such as family disruptions, financial worries, and changing roles within relationships. To help meet these needs, some support groups are designed just for family members of people diagnosed with cancer; other groups encourage families and friends to participate along with the cancer patient or cancer survivor. How Can People Find Support Groups? Many organizations offer support groups for people diagnosed with cancer and their family members or friends. The NCI fact sheet National Organizations That Offer Services to People with Cancer and Their Families lists many cancer-concerned organizations that can provide information about support groups. This fact sheet is available at http://cis.nci.nih.gov/fact/8_1.htm on the Internet, or can be ordered from the Cancer Information Service at 1–800–4–CANCER (1–800–422–6237). Some of these organizations provide information on their Web sites about contacting support groups. Doctors, nurses, or hospital social workers who work with cancer patients may also have information about support groups, such as their location, size, type, and how often they meet. Most hospitals have social services departments that provide information about cancer support programs.

Seeking Guidance 31

Additionally, many newspapers carry a special health supplement containing information about where to find support groups.

What Types of Support Groups Are Available? Several kinds of support groups are available to meet the individual needs of people at all stages of cancer treatment, from diagnosis through follow-up care. Some groups are general cancer support groups, while more specialized groups may be for teens or young adults, for family members, or for people affected by a particular disease. Support groups may be led by a professional, such as a psychiatrist, psychologist, or social worker, or by cancer patients or survivors. In addition, support groups can vary in approach, size, and how often they meet. Many groups are free, but some require a fee (people can contact their health insurance company to find out whether their plan will cover the cost). It is important for people to find an atmosphere that is comfortable and meets their individual needs. Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective.

The Cancer Information Service12 The Cancer Information Service (CIS) is a program of the National Cancer Institute (NCI), the Nation’s lead agency for cancer research. As a resource for information and education about cancer, the CIS is a leader in helping people become active participants in their own health care by providing the latest information on cancer in understandable language. Through its

12

This section has been adapted from the NCI: http://cis.nci.nih.gov/fact/2_5.htm.


network of regional offices, the CIS serves the United States, Puerto Rico, the U.S. Virgin Islands, and the Pacific Islands. For 25 years, the Cancer Information Service has provided the latest and most accurate cancer information to patients and families, the public, and health professionals by: ·

Interacting with people one-on-one through its Information Service,

·

Working with organizations through its Partnership Program,

·

Participating in research efforts to find the best ways to help people adopt healthier behaviors,

·

Providing access to NCI information over the Internet. How Does the CIS Assist the Public?

Through the CIS toll-free telephone service (1–800–4–CANCER), callers speak with knowledgeable, caring staff who are experienced at explaining medical information in easy-to-understand terms. CIS information specialists answer calls in English and Spanish. They also provide cancer information to deaf and hard of hearing callers through the toll-free TTY number (1–800– 332–8615). CIS staff have access to comprehensive, accurate information from the NCI on a range of cancer topics, including the most recent advances in cancer treatment. They take as much time as each caller needs, provide thorough and personalized attention, and keep all calls confidential. The CIS also provides live, online assistance to users of NCI Web sites through LiveHelp, an instant messaging service that is available from 9:00 a.m. to 7:30 p.m. Eastern time, Monday through Friday. Through LiveHelp, information specialists provide answers to questions about cancer and help in navigating Cancer.gov, the NCI’s Web site. Through the telephone numbers or LiveHelp service, CIS users receive: ·

Answers to their questions about cancer, including ways to prevent cancer, symptoms and risks, diagnosis, current treatments, and research studies;

·

Written materials from the NCI;

·

Referrals to clinical trials and cancer-related services, such as treatment centers, mammography facilities, or other cancer organizations;

·

Assistance in quitting smoking from information specialists trained in smoking cessation counseling.

Seeking Guidance 33

What Kind of Assistance Does the CIS Partnership Program Offer? Through its Partnership Program, the CIS collaborates with established national, state, and regional organizations to reach minority and medically underserved audiences with cancer information. Partnership Program staff provide assistance to organizations developing programs that focus on breast and cervical cancer, clinical trials, tobacco control, and cancer awareness for special populations. To reach those in need, the CIS: ·

Helps bring cancer information to people who do not traditionally seek health information or who may have difficulties doing so because of educational, financial, cultural, or language barriers;

·

Provides expertise to organizations to help strengthen their ability to inform people they serve about cancer; and

·

Links organizations with similar goals and helps them plan and evaluate programs, develop coalitions, conduct training on cancer-related topics, and use NCI resources. How Do CIS Research Efforts Assist the Public?

The CIS plays an important role in research by studying the most effective ways to communicate with people about healthy lifestyles; health risks; and options for preventing, diagnosing, and treating cancer. The ability to conduct health communications research is a unique aspect of the CIS. Results from these research studies can be applied to improving the way the CIS communicates about cancer and can help other programs communicate more effectively. How Do People Reach the Cancer Information Service? ·

To speak with a CIS information specialist call 1–800–4–CANCER (1–800– 422–6237), 9:00 a.m. to 4:30 p.m. local time, Monday through Friday. Deaf or hard of hearing callers with TTY equipment may call 1–800–332–8615.

·

To obtain online assistance visit the NCI’s Cancer Information Web site at http://cancer.gov/cancer_information and click on the LiveHelp link between 9:00 a.m. and 7:30 p.m. Eastern time, Monday through Friday.

·

For information 24 hours a day, 7 days a week call 1–800–4–CANCER and select option 4 to hear recorded information at any time.

·

Visit NCI’s Web site at http://cancer.gov on the Internet.

·

Visit the CIS Web site at http://cancer.gov/cis on the Internet.


Finding Cancer Resources in Your Community13 If you have cancer or are undergoing cancer treatment, there are places in your community to turn to for help. There are many local organizations throughout the country that offer a variety of practical and support services to people with cancer. However, people often don’t know about these services or are unable to find them. National cancer organizations can assist you in finding these resources, and there are a number of things you can do for yourself. Whether you are looking for a support group, counseling, advice, financial assistance, transportation to and from treatment, or information about cancer, most neighborhood organizations, local health care providers, or area hospitals are a good place to start. Often, the hardest part of looking for help is knowing the right questions to ask. What Kind of Help Can I Get? Until now, you probably never thought about the many issues and difficulties that arise with a diagnosis of cancer. There are support services to help you deal with almost any type of problem that might occur. The first step in finding the help you need is knowing what types of services are available. The following pages describe some of these services and how to find them. ·

Information on Cancer. Most national cancer organizations provide a range of information services, including materials on different types of cancer, treatments, and treatment-related issues.

·

Counseling. While some people are reluctant to seek counseling, studies show that having someone to talk to reduces stress and helps people both mentally and physically. Counseling can also provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, self-help (sometimes called peer counseling), bereavement, patient-to-patient, and sexuality.

·

Medical Treatment Decisions. Often, people with cancer need to make complicated medical decisions. Many organizations provide hospital and physician referrals for second opinions and information on clinical trials (research studies with people), which may expand treatment options.

13

Adapted from the NCI: http://cis.nci.nih.gov/fact/8_9.htm.

Seeking Guidance 35

·

Prevention and Early Detection. While cancer prevention may never be 100 percent effective, many things (such as quitting smoking and eating healthy foods) can greatly reduce a person’s risk for developing cancer. Prevention services usually focus on smoking cessation and nutrition. Early detection services, which are designed to detect cancer when a person has no symptoms of disease, can include referrals for screening mammograms, Pap tests, or prostate exams.

·

Home Health Care. Home health care assists patients who no longer need to stay in a hospital or nursing home, but still require professional medical help. Skilled nursing care, physical therapy, social work services, and nutrition counseling are all available at home.

·

Hospice Care. Hospice is care focused on the special needs of terminally ill cancer patients. Sometimes called palliative care, it centers around providing comfort, controlling physical symptoms, and giving emotional support to patients who can no longer benefit from curative treatment. Hospice programs provide services in various settings, including the patient’s home, hospice centers, hospitals, or skilled nursing facilities. Your doctor or social worker can provide a referral for these services.

·

Rehabilitation. Rehabilitation services help people adjust to the effects of cancer and its treatment. Physical rehabilitation focuses on recovery from the physical effects of surgery or the side effects associated with chemotherapy. Occupational or vocational therapy helps people readjust to everyday routines, get back to work, or find employment.

·

Advocacy. Advocacy is a general term that refers to promoting or protecting the rights and interests of a certain group, such as cancer patients. Advocacy groups may offer services to assist with legal, ethical, medical, employment, legislative, or insurance issues, among others. For instance, if you feel your insurance company has not handled your claim fairly, you may want to advocate for a review of its decision.

·

Financial. Having cancer can be a tremendous financial burden to cancer patients and their families. There are programs sponsored by the government and nonprofit organizations to help cancer patients with problems related to medical billing, insurance coverage, and reimbursement issues. There are also sources for financial assistance, and ways to get help collecting entitlements from Medicaid, Medicare, and the Social Security Administration.

·

Housing/Lodging. Some organizations provide lodging for the family of a patient undergoing treatment, especially if it is a child who is ill and the parents are required to accompany the child to treatment.


·

Children’s Services. A number of organizations provide services for children with cancer, including summer camps, make-a-wish programs, and help for parents seeking child care. How to Find These Services

Often, the services that people with cancer are looking for are right in their own neighborhood or city. The following is a list of places where you can begin your search for help. ·

The hospital, clinic, or medical center where you see your doctor, received your diagnosis, or where you undergo treatment should be able to give you information. Your doctor or nurse may be able to tell you about your specific medical condition, pain management, rehabilitation services, home nursing, or hospice care.

·

Most hospitals also have a social work, home care, or discharge planning department. This department may be able to help you find a support group, a nonprofit agency that helps people who have cancer, or the government agencies that oversee Social Security, Medicare, and Medicaid. While you are undergoing treatment, be sure to ask the hospital about transportation, practical assistance, or even temporary child care. Talk to a hospital financial counselor in the business office about developing a monthly payment plan if you need help with hospital expenses.

·

The public library is an excellent source of information, as are patient libraries at many cancer centers. A librarian can help you find books and articles through a literature search.

·

A local church, synagogue, YMCA or YWCA, or fraternal order may provide financial assistance, or may have volunteers who can help with transportation and home care. Catholic Charities, the United Way, or the American Red Cross may also operate local offices. Some of these organizations may provide home care, and the United Way’s information and referral service can refer you to an agency that provides financial help. To find the United Way serving your community, visit their online directory at http://www.unitedway.org on the Internet or look in the White Pages of your local telephone book.

·

Local or county government agencies may offer low-cost transportation (sometimes called para-transit) to individuals unable to use public transportation. Most states also have an Area Agency on Aging that offers low-cost services to people over 60. Your hospital or community social worker can direct you to government agencies for entitlements,

Seeking Guidance 37

including Social Security, state disability, Medicaid, income maintenance, and food stamps. (Keep in mind that most applications to entitlement programs take some time to process.) The Federal government also runs the Hill-Burton program (1–800–638–0742), which funds certain medical facilities and hospitals to provide cancer patients with free or low-cost care if they are in financial need. Getting the Most From a Service: What To Ask No matter what type of help you are looking for, the only way to find resources to fit your needs is to ask the right questions. When you are calling an organization for information, it is important to think about what questions you are going to ask before you call. Many people find it helpful to write out their questions in advance, and to take notes during the call. Another good tip is to ask the name of the person with whom you are speaking in case you have follow-up questions. Below are some of the questions you may want to consider if you are calling or visiting a new agency and want to learn about how they can help: ·

How do I apply [for this service]?

·

Are there eligibility requirements? What are they?

·

Is there an application process? How long will it take? What information will I need to complete the application process? Will I need anything else to get the service?

·

Do you have any other suggestions or ideas about where I can find help?

The most important thing to remember is that you will rarely receive help unless you ask for it. In fact, asking can be the hardest part of getting help. Don’t be afraid or ashamed to ask for assistance. Cancer is a very difficult disease, but there are people and services that can ease your burdens and help you focus on your treatment and recovery.

Finding Doctors Who Specialize in Cancer Care14 One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with chronic lymphocytic leukemia must go through the process of selecting a physician. A common way to find a doctor who specializes in cancer care is to ask for a referral from your primary care physician. Sometimes, you may know a 14

Adapted from the NCI: http://cis.nci.nih.gov/fact/7_47.htm.


specialist yourself, or through the experience of a family member, coworker, or friend. The following resources may also be able to provide you with names of doctors who specialize in treating specific diseases or conditions. However, these resources may not have information about the quality of care that the doctors provide. ·

Your local hospital or its patient referral service may be able to provide you with a list of specialists who practice at that hospital.

·

Your nearest National Cancer Institute (NCI)-designated cancer center can provide information about doctors who practice at that center. The NCI fact sheet The National Cancer Institute Cancer Centers Program describes and gives contact information, including Web sites, for NCIdesignated cancer treatment centers around the country. Many of the cancer centers’ Web sites have searchable directories of physicians who practice at each facility. The NCI’s fact sheet is available at http://cis.nci.nih.gov/fact/1_2.htm on the Internet, or by calling the Cancer Information Service (CIS) at 1–800–4–CANCER (1–800–422–6237).

·

The American Board of Medical Specialties (ABMS) publishes a list of board-certified physicians. The Official ABMS Directory of Board Certified Medical Specialists lists doctors’ names along with their specialty and their educational background. This resource is available in most public libraries. The ABMS also has a Web site that can be used to verify whether a specific physician is board-certified. This free service is located at http://www.abms.org/newsearch.asp on the Internet. Verification of a physician’s board certification can also be obtained by calling the ABMS at 1–866–275–2267 (1–866–ASK–ABMS).

·

The American Medical Association (AMA) provides an online service called AMA Physician Select that offers basic professional information on virtually every licensed physician in the United States and its possessions. The database can be searched by doctor’s name or by medical specialty. The AMA Physician Select service is located at http://www.ama-assn.org/aps/amahg.htm on the Internet.

·

The American Society of Clinical Oncologists (ASCO) provides an online list of doctors who are members of ASCO. The member database has the names and affiliations of over 15,000 oncologists worldwide. It can be searched by doctor’s name, institution’s name, location, and/or type of board certification. This service is located at http://www.asco.org/people/db/html/m_db.htm on the Internet.

Seeking Guidance 39

·

The American College of Surgeons (ACOS) Fellowship Database is an online list of surgeons who are Fellows of the ACOS. The list can be searched by doctor’s name, geographic location, or medical specialty. This service is located at http://web.facs.org/acsdir/default.htm on the Internet. The ACOS can be contacted at 633 North Saint Clair Street, Chicago, IL 60611–3211; or by telephone at 312–202–5000.

·

Local medical societies may maintain lists of doctors in each specialty.

·

Public and medical libraries may have print directories of doctors’ names, listed geographically by specialty.

·

Your local Yellow Pages may have doctors listed by specialty under “Physicians.”

The Agency for Healthcare Research and Quality (AHRQ) offers Your Guide to Choosing Quality Health Care, which has information for consumers on choosing a health plan, a doctor, a hospital, or a long-term care provider. The Guide includes suggestions and checklists that you can use to determine which doctor or hospital is best for you. This resource is available at http://www.ahrq.gov/consumer/qntool.htm on the Internet. You can also order the Guide by calling the AHRQ Publications Clearinghouse at 1–800– 358–9295. If you are a member of a health insurance plan, your choice may be limited to doctors who participate in your plan. Your insurance company can provide you with a list of participating primary care doctors and specialists. It is important to ask your insurance company if the doctor you choose is accepting new patients through your health plan. You also have the option of seeing a doctor outside your health plan and paying the costs yourself. If you have a choice of health insurance plans, you may first wish to consider which doctor or doctors you would like to use, then choose a plan that includes your chosen physician(s). The National Comprehensive Cancer Network (NCCN) Physician Directory lists specialists who practice in the NCCN’s 19 member institutions across the U.S. To access the directory, go to http://www.nccn.org/ and click on “Physician Directory“. To use this service, you will be required to scroll to the bottom of the page and select “I agree.” Enter your search criteria and select “Find” at the bottom of the page. To obtain more information on a physician or institution, contact the institution’s Physician Referral Department or the NCCN Patient Information and Referral Service at 1-888909-NCCN or [email protected].


If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Selecting Your Doctor15 There are many factors to consider when choosing a doctor. To make the most informed decision, you may wish to speak with several doctors before choosing one. When you meet with each doctor, you might want to consider the following: ·

Does the doctor have the education and training to meet my needs?

·

Does the doctor use the hospital that I have chosen?

·

Does the doctor listen to me and treat me with respect?

·

Does the doctor explain things clearly and encourage me to ask questions?

·

What are the doctor’s office hours?

·

Who covers for the doctor when he or she is unavailable? Will that person have access to my medical records?

·

How long does it take to get an appointment with the doctor?

If you are choosing a surgeon, you may wish to ask additional questions about the surgeon’s background and experience with specific procedures. These questions may include: ·

Is the surgeon board-certified?16

·

Has the surgeon been evaluated by a national professional association of surgeons, such as the American College of Surgeons (ACOS)?

·

At which treatment facility or facilities does the surgeon practice?

·

How often does the surgeon perform the type of surgery I need?

15 This

section has been adapted from the AHRQ: http://www.ahrq.gov/consumer/qntascii/qntdr.htm 16 While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified.

Seeking Guidance 41

·

How many of these procedures has the surgeon performed? What was the success rate?

It is important for you to feel comfortable with the specialist that you choose, because you will be working closely with that person to make decisions about your cancer treatment. Trust your own observations and feelings when deciding on a doctor for your medical care. Other health professionals and support services may also be important during cancer treatment. The National Cancer Institute fact sheet Your Health Care Team: Your Doctor Is Only the Beginning has information about these providers and services, and how to locate them. This fact sheet is located at http://cis.nci.nih.gov/fact/8_10.htm on the Internet, or can be obtained by calling the CIS at 1–800–4–CANCER (1–800–422–6237).

Working with Your Doctor17 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

·

It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

·

Bring a “health history” list with you (and keep it up to date).

·

Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

·

Tell your doctor about any natural or alternative medicines you are taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don’t, your doctor will assume that you understood everything that was said.

This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

17


·

Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

·

Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

·

Ask your doctor to draw pictures if you think that this would help you understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

·

Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

·

After leaving the doctor’s office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.

Finding a Cancer Treatment Facility18 Choosing a treatment facility is another important consideration for getting the best medical care possible. Although you may not be able to choose which hospital treats you in an emergency, you can choose a facility for scheduled and ongoing care. If you have already found a doctor for your cancer treatment, you may need to choose a facility based on where your doctor practices. Your doctor may be able to recommend a facility that provides quality care to meet your needs. You may wish to ask the following questions when considering a treatment facility: ·

Has the facility had experience and success in treating my condition?

Adapted from the NCI: http://cis.nci.nih.gov/fact/7_47.htm. At this Web site, information on how to find treatment facilities is also available for patients living outside the U.S. 18

Seeking Guidance 43

·

Has the facility been rated by state, consumer, or other groups for its quality of care?

·

How does the facility check and work to improve its quality of care?

·

Has the facility been approved by a nationally recognized accrediting body, such as the American College of Surgeons (ACOS) and/or the Joint Commission on Accredited Healthcare Organizations (JCAHO)?

·

Does the facility explain patients’ rights and responsibilities? Are copies of this information available to patients?

·

Does the treatment facility offer support services, such as social workers and resources to help me find financial assistance if I need it?

·

Is the facility conveniently located?

If you are a member of a health insurance plan, your choice of treatment facilities may be limited to those that participate in your plan. Your insurance company can provide you with a list of approved facilities. Although the costs of cancer treatment can be very high, you have the option of paying out-of-pocket if you want to use a treatment facility that is not covered by your insurance plan. If you are considering paying for treatment yourself, you may wish to discuss the potential costs with your doctor beforehand. You may also want to speak with the person who does the billing for the treatment facility. In some instances, nurses and social workers can provide you with more information about coverage, eligibility, and insurance issues. The following resources may help you find a hospital or treatment facility for your care: ·

The NCI fact sheet The National Cancer Institute Cancer Centers Program describes and gives contact information for NCI-designated cancer treatment centers around the country.

·

The ACOS accredits cancer programs at hospitals and other treatment facilities. More than 1,400 programs in the United States have been designated by the ACOS as Approved Cancer Programs. The ACOS Web site offers a searchable database of these programs at http://web.facs.org/cpm/default.htm on the Internet. The ACOS can be contacted at 633 North Saint Clair Street, Chicago, IL 60611–3211; or by telephone at 312–202–5000.

·

The JCAHO is an independent, not-for-profit organization that evaluates and accredits health care organizations and programs in the United States. It also offers information for the general public about choosing a


treatment facility. The JCAHO Web site is located at http://www.jcaho.org on the Internet. The JCAHO is located at One Renaissance Boulevard, Oakbrook Terrace, IL 60181–4294. The telephone number is 630–792–5800. ·

The JCAHO offers an online Quality Check service that patients can use to determine whether a specific facility has been accredited by the JCAHO and view the organization’s performance reports. This service is located at http://www.jcaho.org/qualitycheck/directry/directry.asp on the Internet.

·

The AHRQ publication Your Guide To Choosing Quality Health Care has suggestions and checklists for choosing the treatment facility that is right for you.

Additional Cancer Support Information In addition to the references above, the NCI has set up guidance Web sites that offers information on issues relating to cancer. These include: ·

Facing Forward - A Guide for Cancer Survivors: http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=cc93a 843-6fc0-409e-8798-5c65afc172fe

·

Taking Time: Support for People With Cancer and the People Who Care About Them: http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=21a4 6445-a5c8-4fee-95a3-d9d0d665077a

·

When Cancer Recurs: Meeting the Challenge: http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=9e13 d0d2-b7de-4bd6-87da-5750300a0dab

·

Your Health Care Team: Your Doctor Is Only the Beginning: http://cis.nci.nih.gov/fact/8_10.htm

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure.

Seeking Guidance 45

Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Mammogram: An x-ray of the breast. [NIH] Mammography: The use of x-rays to create a picture of the breast. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Palliative: 1. affording relief, but not cure. 2. an alleviating medicine. [EU] Pap test: The collection of cells from the cervix for examination under a microscope. It is used to detect changes that may be cancer or may lead to cancer, and can show noncancerous conditions, such as infection or inflammation. Also called a Pap smear. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Screening: Checking for disease when there are no symptoms. [NIH]

Clinical Trials 47

CHAPTER 3. CLINICAL LYMPHOCYTIC LEUKEMIA

TRIALS

AND

CHRONIC

Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning chronic lymphocytic leukemia.

What Is a Clinical Trial?19 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for chronic lymphocytic leukemia is to try it on patients in a clinical trial.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

19


What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on chronic lymphocytic leukemia.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for chronic lymphocytic leukemia compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment.

How Is a Clinical Trial Conducted? Various organizations support clinical trials at medical centers, hospitals, universities, and doctors’ offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on chronic lymphocytic leukemia carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on chronic lymphocytic leukemia. In other clinical trials, where a new surgery or device

Clinical Trials 49

(not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This treatment, like a placebo, has no effect on chronic lymphocytic leukemia and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how chronic lymphocytic leukemia develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for chronic lymphocytic leukemia. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial’s investigators and provide details about your diagnosis and medical history.


If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Chronic Lymphocytic Leukemia The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to chronic lymphocytic leukemia.20 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

Antineoplaston Therapy Myelogenous Leukemia

in

Treating

Patients

With

Chronic

Condition(s): accelerated phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; meningeal chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients who have chronic myelogenous leukemia that has not responded to previous treatment. 20

These are listed at www.ClinicalTrials.gov.

Clinical Trials 51

Phase(s): Phase II Study Type: Treatment Contact(s): Texas; Burzynski Research Institute, Houston, Texas, 77055, United States; Recruiting; Stanislaw R. Burzynski 713-335-5697. Study chairs or principal investigators: Stanislaw R. Burzynski, Study Chair; Burzynski Research Institute Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003503;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Arsenic Trioxide in Treating Patients With Recurrent or Refractory Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia Condition(s): relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; recurrent adult acute lymphoblastic leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); H. Lee Moffitt Cancer Center and Research Institute Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of arsenic trioxide in treating patients who have recurrent or refractory acute lymphoblastic leukemia or chronic myelogenous leukemia. Phase(s): Phase II Study Type: Treatment Contact(s): Florida; H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, 33612-9497, United States; Recruiting; Thomas Patrick Loughran, Jr. 813-903-6841. Study chairs or principal investigators: Thomas Patrick Loughran, Jr., Study Chair; H. Lee Moffitt Cancer Center and Research Institute Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006092;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

·

Bevacizumab, Cytarabine, and Mitoxantrone on Treating Patients With Hematologic Cancers Condition(s): relapsing chronic myelogenous leukemia; recurrent adult acute myeloid leukemia; refractory anemia with excess blasts in


transformation; refractory anemia with excess blasts; chronic myelomonocytic leukemia; secondary acute myeloid leukemia; previously treated myelodysplastic syndromes; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Maryland Greenebaum Cancer Center Purpose - Excerpt: RATIONALE: Monoclonal antibodies such as bevacizumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may be an effective treatment for hematologic cancer. PURPOSE: Phase II trial to study the effectiveness of bevacizumab combined with cytarabine and mitoxantrone in treating patients who have hematologic cancer. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00015951;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Bevacizumab, Idarubicin, and Cytarabine in Treating Patients With Chronic Myelogenous Leukemia Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); M.D. Anderson Cancer Center Purpose - Excerpt: RATIONALE: Monoclonal antibodies such as bevacizumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may be an effective treatment for chronic myelogenous leukemia. PURPOSE: Phase II trial to study the effectiveness of bevacizumab, idarubicin, and cytarabine in treating patients who have chronic myelogenous leukemia. Phase(s): Phase II Study Type: Treatment

Clinical Trials 53

Contact(s): Texas; University of Texas - MD Anderson Cancer Center, Houston, Texas, 77030-4009, United States; Recruiting; Jorge Cortes 713794-5783. Study chairs or principal investigators: Jorge Cortes, Study Chair; M.D. Anderson Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00023920;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Bone Marrow Transplantation in Treating Patients With Multiple Myeloma or Chronic Phase Chronic Myelogenous Leukemia Condition(s): stage I multiple myeloma; stage II multiple myeloma; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; stage III multiple myeloma; agnogenic myeloid metaplasia; refractory plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Robert H. Lurie Cancer Center Purpose - Excerpt: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by the chemotherapy or radiation therapy that was used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of allogeneic bone marrow transplantation in treating patients who have multiple myeloma or chronic phase chronic myelogenous leukemia. Phase(s): Phase II Study Type: Treatment Contact(s): Illinois; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, 60611-3013, United States; Recruiting; Martin Stuart Tallman 312-695-6180. Study chairs or principal investigators: Martin Stuart Tallman, Study Chair; Robert H. Lurie Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004181;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Bone Marrow Transplantation Plus Cyclophosphamide and Radiation Therapy in Treating Patients With Hematologic Cancer Condition(s): accelerated phase chronic myelogenous leukemia; refractory anemia with excess blasts in transformation; refractory anemia


with excess blasts; refractory anemia; recurrent adult acute lymphoblastic leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; bone marrow ablation; refractory chronic lymphocytic leukemia; secondary acute myeloid leukemia; recurrent adult acute myeloid leukemia; previously treated myelodysplastic syndromes; adult acute myeloid leukemia in remission Study Status: This study is currently recruiting patients. Sponsor(s): Fox Chase Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation from an unrelated donor plus cyclophosphamide and radiation therapy in treating patients who have hematologic cancer. Phase(s): Phase II Study Type: Treatment Contact(s): Pennsylvania; Fox Chase - Temple Cancer Center, Philadelphia, Pennsylvania, 19140, United States; Recruiting; Kenneth F. Mangan 215-214-3129. Study chairs or principal investigators: Kenneth F. Mangan, Study Chair; Fox Chase Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002809;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Chemotherapy and Monoclonal Antibody Therapy in Treating Patients With Advanced Myeloid Cancer Condition(s): accelerated phase chronic myelogenous leukemia; untreated adult acute myeloid leukemia; recurrent adult acute myeloid leukemia; untreated childhood acute myeloid leukemia and other myeloid malignancies; refractory anemia with excess blasts in transformation; recurrent childhood acute myeloid leukemia; refractory anemia with excess blasts; secondary myelodysplastic syndromes; chronic myelomonocytic leukemia; previously treated myelodysplastic syndromes; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center

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Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combining chemotherapy and monoclonal antibody therapy in treating patients who have advanced myeloid cancer. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; David A. Scheinberg 212-639-5010. Study chairs or principal investigators: Joseph G. Jurcic, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00014495;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Chemotherapy and Peripheral Stem Cell Transplantation Followed by Immunotherapy in Treating Patients With Chronic Myelogenous Leukemia Condition(s): relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; Philadelphia chromosome negative chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): University of Maryland Greenebaum Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation and immunotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase II trial to study the effectiveness of chemotherapy and peripheral stem cell transplantation followed by immunotherapy in treating patients who have chronic phase chronic myelogenous leukemia. Phase(s): Phase II Study Type: Treatment Contact(s): Maryland; Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, 21201, United States; Recruiting; Aaron P. Rapoport 410-328-1230. Study chairs or principal


investigators: Aaron P. Rapoport, Study Chair; University of Maryland Greenebaum Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003727;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Chemotherapy Plus Sargramostim in Treating Patients With Refractory Myeloid Cancer Condition(s): accelerated phase chronic myelogenous leukemia; untreated adult acute myeloid leukemia; refractory anemia; relapsing chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; recurrent adult acute myeloid leukemia; refractory anemia with ringed sideroblasts; chronic myelomonocytic leukemia; previously treated myelodysplastic syndromes; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Sidney Kimmel Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase I trial to study the effectiveness of bryostatin 1 combined with sargramostim in treating patients who have refractory myeloid cancer. Phase(s): Phase I Study Type: Treatment Contact(s): Maryland; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, 21231-2410, United States; Recruiting; B. Douglas Smith 410-614-5068. Study chairs or principal investigators: B. Douglas Smith, Study Chair; Sidney Kimmel Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00012376;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Chemotherapy, Biological Therapy, and/or Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myelogenous Leukemia Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; Philadelphia chromosome negative chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): III Medizinische Klinik Mannheim Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Interferon alfa may interfere with the growth of cancer cells. It is not yet known if chemotherapy is more effective with or without interferon alfa and/or stem cell or bone marrow transplantation in treating chronic myelogenous leukemia. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without biological therapy and/or stem cell transplantation. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00025402;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Chemotherapy, Interferon, and Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; Philadelphia chromosome negative chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): German CML Study Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens or bone


marrow transplantation in treating patients with chronic myelogenous leukemia. Phase(s): Phase III Study Type: Treatment Contact(s): Germany; III Medizinische Klinik Mannheim, Mannheim, D68135, Germany; Recruiting; Ruediger Hehlmann 49-621-383-4115. Study chairs or principal investigators: Ruediger Hehlmann, Study Chair; German CML Study Group Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002771;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Combination Chemotherapy and Interferon alfa in Treating Patients With Chronic Myelogenous Leukemia Condition(s): relapsing chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Interferon alfa may interfere with the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and interferon alfa in treating patients with chronic myelogenous leukemia. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Mark Adam Weiss 212639-5827. Study chairs or principal investigators: Mark Adam Weiss, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002598;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Combination Chemotherapy in Treating Patients With Chronic Myelogenous Leukemia or Recurrent Acute Leukemia Condition(s): accelerated phase chronic myelogenous leukemia; neutropenia; recurrent adult acute lymphoblastic leukemia; relapsing

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chronic myelogenous leukemia; recurrent adult acute myeloid leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Mayo Clinic Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy with carboplatin and topotecan in treating patients with chronic myelogenous leukemia or recurrent acute leukemia. Phase(s): Phase I Study Type: Treatment Contact(s): Minnesota; Mayo Clinic Cancer Center, Rochester, Minnesota, 55905, United States; Recruiting; Scott Harold Kaufmann 507-284-8950. Study chairs or principal investigators: Scott Harold Kaufmann, Study Chair; Mayo Clinic Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002693;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Combination Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia Condition(s): accelerated phase chronic myelogenous leukemia; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; refractory anemia; relapsing chronic myelogenous leukemia; secondary myelodysplastic syndromes; de novo myelodysplastic syndromes; chronic phase chronic myelogenous leukemia; chronic myelomonocytic leukemia; meningeal chronic myelogenous leukemia; refractory anemia with ringed sideroblasts; previously treated myelodysplastic syndromes; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Leukemia Cooperative Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomized phase III trial to compare the effectiveness of peripheral stem cell transplantation with high-dose


cytarabine in treating patients with myelodysplastic syndrome or acute myelogenous leukemia. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002926;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Comparison of Two Combination Chemotherapy Regimens in Treating Adults With Previously Untreated Leukemia or Lymphoma Condition(s): contiguous stage II adult lymphoblastic lymphoma; stage I adult lymphoblastic lymphoma; Philadelphia chromosome positive chronic myelogenous leukemia; stage II adult lymphoblastic lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; untreated adult acute lymphoblastic leukemia; B-cell adult acute lymphoblastic leukemia; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; T-cell adult acute lymphoblastic leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective for acute lymphoblastic leukemia, lymphoblastic lymphoma, or chronic myelogenous leukemia. PURPOSE: Randomized phase III trial to compare the effectiveness of two chemotherapy regimens in treating adults who have acute lymphoblastic leukemia, lymphoblastic lymphoma, or chronic myelogenous leukemia. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002766;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Cyclophosphamide and Filgrastim Followed By Peripheral Stem Cell Transplantation in Treating Patients With Chronic or Accelerated Phase Myelogenous Leukemia Condition(s): accelerated phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): University of Minnesota Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of cyclophosphamide plus filgrastim followed by autologous peripheral stem cell transplantation in treating patients who have chronic phase or accelerated phase chronic myelogenous leukemia. Phase(s): Phase II Study Type: Treatment Contact(s): Minnesota; University of Minnesota Cancer Center, Minneapolis, Minnesota, 55455, United States; Recruiting; Catherine M. Verfaillie 612-624-3921. Study chairs or principal investigators: Catherine M. Verfaillie, Study Chair; University of Minnesota Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005984;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Dose-Determining Study of R115777 for Childhood Leukemia Condition(s): Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Acute Nonlymphocytic Leukemia; Acute Myelomonocytic Leukemia; Chronic Myelomonocytic Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will determine what dose of R115777 can safely be given to children with leukemia. R115777 interferes with the function of certain proteins that control cell growth. In many types of cancer, including leukemia, one of these proteins, called ras does not function properly, so that cell growth is unchecked. Besides determining a safe dose of R115777, this study will also look at the drug's side effects, its possible benefits in treating childhood leukemia, how the body uses


and eliminates it, and what changes occur in leukemia cells and in the gene that produces the ras protein after giving R115777. Patients 21 years of age or younger with acute lymphoblastic leukemia (ALL), acute nonlymphoblastic leukemia) ANLL), juvenile myelomonocytic leukemia (JMML), or chronic myelogenous leukemia (CML) who do not respond to standard therapy may be eligible for this study. Candidates will be screened with a history and physical examination, eye examination, blood and urine tests, lumbar puncture (spinal tap) and bone marrow aspiration. Lumbar puncture is done to examine the cerebrospinal fluid (CSF), which bathes the brain and spinal cord. After a local anesthetic is administered, a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle. For the bone marrow test, the hip area is anesthetized and a special needle is used to draw bone marrow from the hipbone. Patients enrolled in the study will take R115777 tablets every 12 hours for 21 days, followed by a 7-day rest period, completing one treatment cycle. To determine the highest dose of drug that can be given safely, the starting dose will be low and will be increased gradually in small groups of patients. Treatment cycles will continue unless unacceptable side effects occur or the leukemia does not respond to the drug. Patients will undergo the following tests and procedures to monitor for side effects and evaluate the response of the leukemia to treatment: - Physical examinations - every week, initially Eye examinations - regularly - Blood tests- periodically throughout treatment - Bone marrow examination - before the start of each treatment cycle for three cycles and then less often - Buccal swab (scraping the inside of the cheek with a tongue depressor to collect a cell sample) before the first treatment dose and once during the first treatment cycle. Additional blood samples will be collected as follows: - To study the pharmacology of R115777, 12 small blood samples will be collected on days 1 and 2 after the first dose of R115777, and one sample will be taken between days 6 and 10 during the first treatment cycle only. If possible, the blood will be drawn through an indwelling catheter to avoid multiple needle sticks. - Samples will be collected before the first treatment dose, once during the first treatment cycle, and before cycles 3,6, 9 and 12, to measure the effect of R115777 on a substance called nerve growth factor to see if it can predict which patients may be at risk for developing side effects from R115777 Phase(s): Phase I Study Type: Interventional

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Contact(s): Maryland; National Cancer Institute (NCI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Clinical Studies Support Center/NCI 1-888-624-1937 [email protected] Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00017888;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Hematologic Cancer Condition(s): accelerated phase chronic myelogenous leukemia; untreated adult acute myeloid leukemia; relapsing chronic myelogenous leukemia; de novo myelodysplastic syndromes; recurrent adult acute myeloid leukemia; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; recurrent adult acute lymphoblastic leukemia; secondary myelodysplastic syndromes; chronic myelomonocytic leukemia; secondary acute myeloid leukemia; untreated adult acute lymphoblastic leukemia; previously treated myelodysplastic syndromes; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Maryland Greenebaum Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of flavopiridol combined with cytarabine and mitoxantrone in treating patients who have hematologic cancer. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): Maryland; Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, 21201, United States; Recruiting; Judith E. Karp 410-328-7394; Minnesota; Mayo Clinic Cancer Center, Rochester, Minnesota, 55905, United States; Recruiting; Scott Harold Kaufmann 507-284-8950. Study chairs or principal investigators: Judith E. Karp, Study Chair; University of Maryland Greenebaum Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00016016;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03


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Fludarabine and Total-Body Irradiation Followed By Donor Peripheral Stem Cell Transplantation in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells. Combining imatinib mesylate with fludarabine and totalbody irradiation followed by donor peripheral stem cell transplantation may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of fludarabine and total-body irradiation followed by donor peripheral stem cell transplantation in treating patients who have acute lymphoblastic leukemia or chronic myelogenous leukemia that has responded to previous treatment with imatinib mesylate. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00036738;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Homoharringtonine in Treating Patients With Chronic Myelogenous Leukemia Condition(s): accelerated phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); M.D. Anderson Cancer Center

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Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of homoharringtonine in treating patients who have chronic myelogenous leukemia. Phase(s): Phase I Study Type: Treatment Contact(s): Texas; University of Texas - MD Anderson Cancer Center, Houston, Texas, 77030-4009, United States; Recruiting; Jorge Cortes 713794-5783. Study chairs or principal investigators: Jorge Cortes, Study Chair; M.D. Anderson Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006364;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Imatinib Mesylate and Cytarabine in Treating Patients With Newly Diagnosed Chronic Myeloid Leukemia Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Stichting Hemato-Oncologie voor Volwassenen Nederland Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate and chemotherapy may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate plus cytarabine in treating patients who have newly diagnosed chronic myeloid leukemia. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00028847;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03


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Imatinib Mesylate and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia Condition(s): relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Oregon Cancer Center Purpose - Excerpt: RATIONALE: Imatinib mesylate and interferon alfa may interfere with the growth of the cancer cells. Combining imatinib mesylate and interferon alfa may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate plus interferon alfa in treating patients who have chronic myelogenous leukemia. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00015847;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Children's Oncology Group Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have chronic myelogenous leukemia. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00030394;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Imatinib Mesylate Plus Cytarabine in Treating Patients With Chronic Myelogenous Leukemia Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Oregon Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate plus cytarabine in treating patients who have chronic myelogenous leukemia. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00022490;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Interferon alfa and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining interferon alfa with imatinib mesylate may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining interferon alfa with imatinib mesylate in treating patients who have chronic myelogenous leukemia. Phase(s): Phase I Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Ellin Berman 212-639-


7762. Study chairs or principal investigators: Ellin Berman, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00045422;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Monoclonal Antibody Plus Interleukin-2 in Treating Patients With Leukemia or Lymphoma Condition(s): relapsing chronic myelogenous leukemia; recurrent adult Hodgkin's disease; chronic phase chronic myelogenous leukemia; recurrent adult acute myeloid leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Beth Israel Deaconess Medical Center Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Interleukin-2 may stimulate a person's white blood cells to kill leukemia or lymphoma cells. Combining these two therapies may be an effective treatment for leukemia and lymphoma. PURPOSE: Phase I/II trial to study the effectiveness of monoclonal antibody therapy plus interleukin-2 in treating patients who have leukemia or lymphoma. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): Massachusetts; Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States; Recruiting; Richard P. Junghans 617432-7004. Study chairs or principal investigators: Richard P. Junghans, Study Chair; Beth Israel Deaconess Medical Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002681;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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MS-275 in Treating Patients With Hematologic Cancer Condition(s): accelerated phase chronic myelogenous leukemia; untreated adult acute myeloid leukemia; relapsing chronic myelogenous leukemia; de novo myelodysplastic syndromes; chronic phase chronic myelogenous leukemia; recurrent adult acute myeloid leukemia; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; recurrent adult acute lymphoblastic leukemia; chronic

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myelomonocytic leukemia; secondary acute myeloid leukemia; untreated adult acute lymphoblastic leukemia; previously treated myelodysplastic syndromes; blastic phase chronic myelogenous leukemia; adult acute promyelocytic leukemia (M3); refractory plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Maryland Greenebaum Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of MS-275 in treating patients who have hematologic cancer. Phase(s): Phase I Study Type: Treatment Contact(s): Maryland; Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, 21201, United States; Recruiting; Judith E. Karp 410-328-7394. Study chairs or principal investigators: Judith E. Karp, Study Chair; University of Maryland Greenebaum Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00015925;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

PEG-Intron For Chronic Myelogenous Leukemia Unresponsive To Or Intolerant Of Roferon Or Intron

Patients

Condition(s): Leukemia, Myeloid, Philadelphia-Positive Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center; Schering-Plough Purpose - Excerpt: The purpose of this study is to determine if PEGIntron is better tolerated and more efficacious than standard interferons (Roferon, Intron) in patients with Philadelphia-positive Chronic Myelogeneous Leukemia. These patients should have previously received standard interferon therapy and have been intolerant, resistant, or have relapsed disease. Phase(s): Phase II Study Type: Interventional Contact(s): Texas; M. D. Anderson Cancer Center, Houston, Texas, 77030, United States; Recruiting; Susan R Pilat, RN. BSN 713-745-3296 [email protected]; Razelle Kurzrock, M.D. 713-794-1226


[email protected]; Investigator

Razelle

Kurzrock,

M.D.,

Principal

Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00037882;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myelogenous Leukemia That Has Responded to Imatinib Mesylate Condition(s): accelerated phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Beckman Research Institute Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining imatinib mesylate with peripheral stem cell transplantation may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of peripheral stem cell transplantation in treating patients who have chronic myelogenous leukemia that has responded to previous imatinib mesylate. Phase(s): Phase II Study Type: Treatment, Genetic Contact(s): California; Cancer Center and Beckman Research Institute, City of Hope, Duarte, California, 91010-3000, United States; Recruiting; Ravi Bhatia 626-359-8111 ext 62683; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, 90095-1781, United States; Recruiting; Ronald Paquette 310-825-5608. Study chairs or principal investigators: Ravi Bhatia, Study Chair; Beckman Research Institute Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00041184;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Phase I Study of Lonafarnib and Gleevec in Chronic Myelogenous Leukemia Condition(s): Chronic Myelogenous Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center

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Purpose - Excerpt: The purpose of this study if to investigate the effect of lonafarnib (SCH66336) in combination with Gleevec in the treatment of CML. Phase(s): Phase I Study Type: Interventional Contact(s): Texas; M.D. Anderson Cancer Center, Houston, Texas, 77030, United States; Recruiting; Jorge E Cortes, MD 713-794-5783 [email protected]; Hagop M Kantarjian, MD 713-792-7026 [email protected]; Jorge E Cortes, MD, Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00047502;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Phase I Study of Zarnestra and Gleevec in Chronic Phase Chronic Myelogenous Leukemia Condition(s): Leukemia, Myeloid, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: The purpose of this study is to investigate the most effective dose of R115777 (Zarnestra) and imatinib mesylate (Gleevec) when used in combination, and the safety of this combination. The possible effect of this combination in Chronic Myelogeous Leukemia (CML) will also be investigated. Patients will also be asked to give a small additional amount of blood and bone marrow whenever one of these procedures is done. The purpose of this is to investigate the effect of this therapy on the leukemia cells and understand better how these drugs work together. Phase(s): Phase I Study Type: Interventional Contact(s): Texas; M.D. Anderson Cancer Center, Houston, Texas, 77030, United States; Recruiting; Jorge E Cortes, MD 713-794-5783 [email protected]; Hagop M Kantarjian, MD 713-792-7026 [email protected]; Jorge E Cortes, MD, Principal Investigator; Hagop M Kantarjian, MD, Sub-Investigator Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00040105;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03


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Phase II trial of decitabine in patients with chronic myelogenous leukemia accelerated phase who are refractory to imatinib mesylate (Gleevec) Condition(s): Chronic Myelogenous Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): SuperGen Purpose - Excerpt: To determine the safety and efficacy of decitabine in patients with Philadelphia chromosome-positive chronic myelogenous leukemia accelerated phase that were previously treated with imatinib mesylate (STI 571) and became resistant/refractory or were found to be intolerant to the drug. Phase(s): Phase II Study Type: Interventional Contact(s): Jocelyn Rojas 925-560-0100 Ext. 424 Emel Bayar, MD 925-5600100 Ext. 404; Texas; University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, United States; Recruiting; Jean-Pierre Issa, MD, Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00041990;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Phase II trial of decitabine in patients with chronic myelogenous leukemia blast phase who are refractory to imatinib mesylate (Gleevec) Condition(s): Chronic Myelogenous Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): SuperGen Purpose - Excerpt: To determine the safety and efficacy of decitabine in patients with Philadelphia chromosome-positive chronic myelogenous leukemia blastic phase that were previously treated with imatinib mesylate (STI 571) and became resistant/refractory or were found to be intolerant to the drug. Phase(s): Phase II Study Type: Interventional Contact(s): Jocelyn Rojas 925-560-0100 Ext. 424 Emel Bayar, MD 925-5600100 Ext. 404; Texas; University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, United States; Recruiting; Jean-Pierre Issa, MD, Principal Investigator

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Phase II trial of decitabine in patients with chronic myelogenous leukemia chronic phase who are refractory to imatinib mesylate (Gleevec) Condition(s): Chronic Myelogenous Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): SuperGen Purpose - Excerpt: To determine the safety and efficacy of decitabine in patients with Philadelphia chromosome-positive chronic myelogenous leukemia chronic phase that were previously treated with imatinib mesylate (STI 571) and became resistant/refractory or were found to be intolerant to the drug. Phase(s): Phase II Study Type: Interventional Contact(s): Jocelyn Rojas 925-560-0100 Ext. 424 Emel Bayar, MD 925-5600100 Ext. 404; Texas; University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, United States; Recruiting; Jean-Pierre Issa, MD, Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00042016;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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PS-341 in Treating Patients With Chronic Myelogenous Leukemia Condition(s): accelerated phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); M.D. Anderson Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of PS-341 in treating patients who have chronic myelogenous leukemia in accelerated phase. Phase(s): Phase II


Study Type: Treatment Contact(s): Texas; University of Texas - MD Anderson Cancer Center, Houston, Texas, 77030-4009, United States; Recruiting; Jorge Cortes 713794-5783. Study chairs or principal investigators: Jorge Cortes, Study Chair; M.D. Anderson Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00023881;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

R115777 in Treating Patients With Myeloproliferative Disorders Condition(s): accelerated phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; Philadelphia chromosome negative chronic myelogenous leukemia; chronic myelomonocytic leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Stanford University Purpose - Excerpt: RATIONALE: R115777 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase I/II trial to study the effectiveness of R115777 in treating patents who have myeloproliferative disorders. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): California; Stanford University Medical Center, Stanford, California, 94305-5408, United States; Recruiting; Peter L. Greenberg 650725-8355; Veterans Affairs Medical Center - Palo Alto, Palo Alto, California, 94304, United States; Recruiting; Peter L. Greenberg 650-7258355. Study chairs or principal investigators: Peter L. Greenberg, Study Chair; Stanford University Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005846;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Radiation Therapy and Biological Therapy in Treating Older Patients With Chronic Myeloid Leukemia Condition(s): accelerated phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients.

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Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by radiation therapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of total-body irradiation followed by peripheral stem cell transplantation in treating older patients with chronic myeloid leukemia. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003145;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Radiolabeled Monoclonal Antibody Therapy and Etoposide Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Myelodysplastic Syndrome or Refractory Leukemia Condition(s): accelerated phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; recurrent adult acute myeloid leukemia; recurrent adult acute lymphoblastic leukemia; previously treated myelodysplastic syndromes; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and deliver radiation to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of radiation and chemotherapy drugs and kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy plus etoposide followed by peripheral stem cell transplantation in treating patients who have advanced myelodysplastic syndrome or refractory leukemia. Phase(s): Phase I Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; David A. Scheinberg


212-639-5010. Study chairs or principal investigators: Peter Maslak, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006040;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Sargramostim Following Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia Condition(s): accelerated phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; Philadelphia chromosome negative chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Sidney Kimmel Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood, and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of allogeneic bone marrow transplantation followed by sargramostim in treating patients who have chronic myelogenous leukemia. Phase(s): Phase II Study Type: Treatment Contact(s): Maryland; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, 21231-2410, United States; Recruiting; B. Douglas Smith 410-614-5068. Study chairs or principal investigators: B. Douglas Smith, Study Chair; Sidney Kimmel Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002778;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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STI571 in Treating Patients With Recurrent Leukemia Condition(s): relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; recurrent childhood acute myeloid leukemia; recurrent childhood acute lymphoblastic leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Children's Cancer Group; Pediatric Oncology Group Purpose - Excerpt: RATIONALE: STI571 may interfere with the growth of cancer cells and may be an effective treatment for leukemia. PURPOSE: Phase I trial to study the effectiveness of STI571 in treating patients who have recurrent leukemia. Phase(s): Phase I Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004932;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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STI571 Plus Combination Chemotherapy in Treating Patients With Chronic Myelogenous Leukemia or Acute Lymphocytic Leukemia Condition(s): relapsing chronic myelogenous leukemia; recurrent adult acute lymphoblastic leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Jonsson Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. STI571 may stop the growth of leukemia cells. Combining chemotherapy and STI571 may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus STI571 in treating patients who have chronic myelogenous leukemia or acute lymphocytic leukemia. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): see Web site below



STI571 Plus Cytarabine Myelogenous Leukemia

in

Treating

Patients

With

Chronic

Condition(s): relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Jonsson Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. STI571 may stop the growth of leukemia cells. Combining chemotherapy and STI571 may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combining STI571 and chemotherapy in treating patients who have chronic myelogenous leukemia. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00015834;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Total-Body Irradiation Plus Chemotherapy Followed By Donor Bone Marrow Transplantation in Treating Children With Hematologic Cancer Condition(s): accelerated phase chronic myelogenous leukemia; recurrent childhood small noncleaved cell lymphoma; relapsing chronic myelogenous leukemia; childhood acute myeloid leukemia in remission; de novo myelodysplastic syndromes; chronic phase chronic myelogenous leukemia; recurrent childhood lymphoblastic lymphoma; recurrent childhood large cell lymphoma; secondary myelodysplastic syndromes; secondary acute myeloid leukemia; previously treated myelodysplastic syndromes; childhood acute lymphoblastic leukemia in remission Study Status: This study is currently recruiting patients.

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Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy xrays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Eliminating the T cells from the donor cells before transplanting them may prevent this from happening. PURPOSE: Phase II trial to study the effectiveness of totalbody irradiation and chemotherapy followed by T-cell depleted donor bone marrow transplantation in treating children who have hematologic cancer . Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Nancy A. Kernan 212639-7250. Study chairs or principal investigators: Nancy A. Kernan, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00028730;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Vaccine Therapy in Treating Patients With Chronic Myelogenous Leukemia Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): University of Connecticut Purpose - Excerpt: RATIONALE: Vaccines made from a person's white blood cells may make the body build an immune response to kill tumor cells. PURPOSE: Phase I trial to study the effectiveness of vaccine therapy in treating patients who have chronic myelogenous leukemia. Phase(s): Phase I Study Type: Treatment Contact(s): Connecticut; University of Connecticut Health Center, Farmington, Connecticut, 06360-7106, United States; Recruiting; Zihai Li


860-679-7979. Study chairs or principal investigators: Zihai Li, Study Chair; University of Connecticut Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00030303;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03 ·

Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome Condition(s): accelerated phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; adult acute myeloid leukemia in remission; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; previously treated myelodysplastic syndromes Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); M.D. Anderson Cancer Center Purpose - Excerpt: RATIONALE: Vaccines made from peptides that are found on leukemia cells may make the body build an immune response and kill cancer cells. Combining vaccine therapy with the immune adjuvant Montanide ISA-51 may be a more effective treatment for chronic myeloid leukemia, acute myeloid leukemia, or myelodysplastic syndrome. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy plus Montanide ISA-51 in treating patients who have chronic myeloid leukemia, acute myeloid leukemia, or myelodysplastic syndrome. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): Texas; University of Texas - MD Anderson Cancer Center, Houston, Texas, 77030-4009, United States; Recruiting; Jeffrey J. Molldrem 713-745-7820. Study chairs or principal investigators: Jeffrey J. Molldrem, Study Chair; M.D. Anderson Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004918;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Modified Bone Marrow Stem Cell Transplantation for Chronic Myelogenous Leukemia Condition(s): Chronic Myeloid Leukemia; Graft vs Host Disease

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Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will investigate the safety and effectiveness of a new stem cell transplant procedure for treating chronic myelogenous leukemia (CML). Transplantation of donated stem cells (cells produced by the bone marrow that mature into the different blood componentswhite cells, red cells and platelets) is a very effective treatment for CML. However, despite its success in a large number of patients, there is still a significant risk of death from the procedure. In addition, it results in sterility and leaves patients at increased risk for other cancers and for eye cataracts. These complications result from the intensive chemotherapy and radiation patients receive before the transplant to rid the body of cancer cells. In this study, radiation will not be used and chemotherapy drugs will be given in lower doses to try to reduce the dangers of the procedure. Patients with CML will be tested for matching with a donor (family member) and will undergo a medical history, physical examination and several tests (e.g., breathing tests, X-rays, and others) to determine eligibility for the study. Participants will then undergo apheresis to collect lymphocytes (white blood cells important in the immune system). In apheresis, whole blood is drawn through a needle in the arm, similar to donating a unit of blood. The required component-in this case, lymphocytes-are separated and removed, and the rest of the blood is returned through a needle in the other arm. Each day starting five days before the transplant, the donor will be given an injection of GCSF, a drug that releases stem cells from the bone marrow into the blood stream. The cells will be collected after the fifth injection and again after a sixth injection the following day. Meanwhile, patients will be given cyclophosphamide and fludarabine, and perhaps anti-thymocyte globulin, to prevent rejection of the donated cells. On the day of the transplant, patients will be given cyclosporin to prevent graft-versushost-disease, a disease in which the donor cells react against the patient's cells. They may also be given lymphocytes after the transplant to boost the immune system and destroy leukemia cells. After 30, 60 and 100 days, bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin. If less than 100 percent are of donor origin, more lymphocytes will be transfused. Patients will have physical examinations and blood tests at least weekly for 3 months and then periodically for 5 years. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States



Oblimersen Plus Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia Condition(s): relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Cancer Institute (NCI); Cancer and Leukemia Group B Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Oblimersen may help imatinib mesylate kill more cancer cells by making cancer cells more sensitive to the drug. PURPOSE: Phase II trial to study the effectiveness of combining oblimersen with imatinib mesylate in treating patients who have chronic myelogenous leukemia that has not responded to treatment with imatinib mesylate. Phase(s): Phase II Study Type: Treatment Contact(s): Richard L. Schilsky 773-834-3914. Study chairs or principal investigators: Richard L. Schilsky, Study Chair; Cancer and Leukemia Group B Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00049192;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

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Therapy of Early Chronic Phase Chronic Myelogenous Leukemia with Gleevec, Alpha Interferon, and Ara-C Condition(s): Leukemia, Myeloid, Chronic-Phase Study Status: This study is suspended. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: The goal of this clinical research study is to see if imatinib mesylate (Gleevec, STI571) with or without IFNa and ara-C can improve CML in chronic phase. Phase(s): Phase II Study Type: Interventional

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Contact(s): Texas; M.D. Anderson Cancer Center, Houston, Texas, 77030, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00048672;jsessionid=60134A F09EB66F8C12A3A6E20B1F6D03

Benefits and Risks21 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment for chronic lymphocytic leukemia. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

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If the treatment is effective, then it may improve health or prevent diseases or disorders.

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Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

·

People who take part in trials contribute to scientific discoveries that may help other people with chronic lymphocytic leukemia. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial’s risks and benefits, the researcher’s expectations of you, and your rights as a patient.

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f291. 21


What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you receive may cause side effects that are serious enough to require medical attention.

How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital’s Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent.

What Are a Patient’s Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

·

Know how the researchers plan to carry out the study, for how long, and where.

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Know what is expected of you.

·

Know any costs involved for you or your insurance provider.

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Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

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Talk openly with doctors and ask any questions.

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After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

·

Receive any new information about the new treatment.

·

Continue to ask questions and get answers.

·

Maintain your privacy. Your name will not appear in any reports based on the study.

·

Know whether you participated in the treatment group or the control group (once the study has been completed). What Should You Ask before Deciding to Join a Clinical Trial?

Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

·

What are the standard treatments for chronic lymphocytic leukemia? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

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What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

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How long will the treatment last? How often will I have to come back for follow-up exams?

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What are the treatment’s possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

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Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

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How will my health be monitored?

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Where will I need to go for the clinical trial? How will I get there?

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How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

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Will I be able to see my own doctor? Who will be in charge of my care?

·

Will taking part in the study affect my daily life? Do I have time to participate?


·

How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Clinical Trials and Insurance Coverage22 As you consider enrolling in a clinical trial, you will face the critical issue of how to cover the costs of care. Even if you have health insurance, your coverage may not include some or all of the patient care costs associated with a clinical trial. This is because some health plans define clinical trials as “experimental” or “investigational” procedures. Because lack of coverage for these costs can keep people from enrolling in trials, the National Cancer Institute is working with major health plans and managed care groups to find solutions. In the meantime, there are strategies that may help you deal with cost and coverage barriers. This section answers frequently asked questions about insurance coverage for clinical trial participation and directs you to additional information resources. The material here is mainly concerned with treatment clinical trials, since other types of trials (prevention, screening, etc.) are newer and generally not covered by health insurance at all. However, this guide may become more relevant for prevention and other types of trials as these trials grow more common. If you do not have any health insurance, you may find this section helpful for understanding some of the costs that trials involve.

What Costs Do Trials Involve? Who Is Usually Responsible for Paying Them? There are two types of costs associated with a trial: patient care costs and research costs. Patient care costs fall into two categories: ·

Usual care costs, such as doctor visits, hospital stays, clinical laboratory tests, x-rays, etc., which occur whether you are participating in a trial or

Adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=1d92be79-8748-4bda-80052a56d332463b.

22

Clinical Trials 87

receiving standard treatment. These costs have usually been covered by a third-party health plan, such as Medicare or private insurance. ·

Extra care costs associated with clinical trial participation, such as the additional tests that may or may not be fully covered by the clinical trial sponsor and/or research institution.

The sponsor and the participant’s health plan need to resolve coverage of these costs for particular trials. Research costs are those associated with conducting the trial, such as data collection and management, research physician and nurse time, analysis of results, and tests purely performed for research purposes. Such costs are usually covered by the sponsoring organization, such as NCI or a pharmaceutical company.

Criteria Used by Health Plans to Make Reimbursement Decisions about Trials Health insurance companies and managed care companies decide which health care services they will pay for by developing coverage policy regarding the specific services. In general, the most important factor determining whether something is covered is a health plan’s judgment as to whether the service is established or investigational. Health plans usually designate a service as established if there is a certain amount of scientific data to show that it is safe and effective. If the health plan does not think that such data exist in sufficient quantity, the plan may label the service as investigational. Health care services delivered within the setting of a clinical trial are very often categorized as investigational and not covered. This is because the health plan thinks that the major reason to perform the clinical trial is that there is not enough data to establish the safety and effectiveness of the service being studied. Thus, for some health plans, any mention of the fact that the patient is involved in a clinical trial results in a denial of payment. Your health plan may define specific criteria that a trial must meet before extending coverage, such as the following:


Sponsorship Some plans may only cover costs of trials sponsored by organizations whose review and oversight of the trial is careful and scientifically rigorous, according to standards set by the health plan.

Trial Phase and Type Some plans may cover patient care costs only for the clinical trials they judge to be “medically necessary” on a case-by-case basis. Trial phase may also affect coverage; for example, while a plan may be willing to cover costs associated with Phase III trials, which include treatments that have already been successful with a certain number of people, the plan may require some documentation of effectiveness before covering a Phase I or II trial. While health plans are interested in efforts to improve prevention and screening, they currently seem less likely to have a review process in place for these trials. Therefore, it may be more difficult to get coverage for the care costs associated with them. Some plans, especially smaller ones, will not cover any costs associated with a clinical trial. Policies vary widely, but in most cases your best bet is to have your doctor initiate discussions with the health plan. Cost “Neutrality” Some health plans may limit coverage to trials they consider cost-neutral (i.e., not significantly more expensive than the treatments considered standard). Lack of Standard Therapy Some plans limit coverage of trials to situations in which no standard therapy is available. Facility and Personnel Qualifications A health plan may require that the facility and medical staff meet specific qualifications to conduct a trial involving unique services, especially

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intensive therapy such as a bone marrow transplant chemotherapy with bone marrow/ stem cell rescue).

(high-dose

Clinical Trials and Medicare Coverage For up-to-date information about Medicare coverage of clinical trials, go to the Web site for the Centers for Medicaid & Medicare (http://www.hcfa.gov/coverage/8d.htm; formerly the Health Care Financing Administration). As of January 2001, the following information was accurate23: What Will Medicare Pay? ·

Anything normally covered is still covered when it is part of a clinical trial. This includes test, procedures, and doctor visits that are ordinarily covered.

·

Anything normally covered even if it is a service or item associated with the experimental treatment. For example, Medicare will pay for the intravenous administration of a new chemotherapy drug being tested in a trial, including any therapy to prevent side effects from the new drug.

·

Anything normally covered even if it resulted from your being in the clinical trial. For example, a test or hospitalization resulting from a side effect of the new treatment that Medicare would ordinarily cover. What Costs Are Not Covered?

·

Investigational items or services being tested in a trial. Sponsors of clinical trials often provide the new drug free, but make sure you ask your doctor before you begin.

·

Items or services used solely for the data collection needs of the trial.

·

Anything being provided free by the sponsor of the trial.

On June 7, 2000, Present Clinton announced that Medicare would revise its payment policy to reimburse the routine patient care costs of clinical trials. The announcement is available for public viewing at the following Web address: http://www.cancer.gov/clinical_trials/doc.aspx?viewid=320DD013-BA7A-4177-A0002011089F34A0.

23


What Kinds of Clinical Trials Are Covered? NCI’s Cancer Information Service has provided a fact sheet for Medicare beneficiaries at the following Web site: http://cis.nci.nih.gov/fact/8_14.htm. In general, cancer treatment and diagnosis trials are covered if: ·

They are funded by the National Cancer Institute (NCI), NCI-Designated Cancer Centers, NCI-Sponsored Clinical Trials Cooperative Groups and all other Federal agencies that fund cancer research. Other trials may be eligible for coverage and doctors can ask Medicare to pay the patients’ costs. Ask your doctor about this before you begin.

·

They are designed to treat or diagnose your cancer.

·

The purpose or subject of the trial is within a Medicare benefit category. For example, cancer diagnosis and treatment are Medicare benefits, so these trials are covered. Cancer prevention trials are not currently covered.

Increasing the Likelihood of Insurance Coverage for Trials24 There are several steps you can follow to deal with coverage issues up front when deciding to enter a clinical trial. Along the way, enlist the help of family members and your doctor or other health professionals. You may find the following checklist useful:

Understand the Costs Associated with the Trial Ask your doctor or the trial’s contact person about the costs that must be covered by you or your health plan. Are these costs significantly higher than those associated with standard care? Also, inquire about the experience of other patients in the trial. Have their plans paid for their care? Have there been any persistent problems with coverage? How often have the trial’s administrators been successful in getting plans to cover patient care costs?

This section has been adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=1d92be79-8748-4bda-80052a56d332463b&docid=0df4397a-eccb-465f-bd33-a89e7a708c46.

24

Clinical Trials 91

Understand Your Health Plan Be sure you know what’s in your policy; request and carefully review the actual contract language. If there’s a specific exclusion for “experimental treatment,” look closely at the policy to see how the plan defines such treatment and under what conditions it might be covered. If it is not clearly defined, call the plan’s customer service line, consult their Web site, and/or write to them. Ask for specific information about clinical trials coverage.

Work Closely with Your Doctor Talk with your doctor about the paperwork he or she submits to your health plan. If there have been problems with coverage in the past, you might ask your doctor or the hospital to send an information package to the plan that includes studies supporting the procedure’s safety, benefits, and medical appropriateness. This package might include: ·

Publications from peer-reviewed literature about the proposed therapy that demonstrate patient benefits;

·

A letter that uses the insurance contract’s own language to explain why the treatment, screening method, or preventive measure should be covered;

·

Letters from researchers that explain the clinical trial;

·

Support letters from patient advocacy groups.

Be sure to keep your own copy of any materials that the doctor sends to your health plan for future reference. Work Closely with Your Company’s Benefits Manager This person may be helpful in enlisting the support of your employer to request coverage by the health plan. Give Your Health Plan a Deadline Ask the hospital or cancer center to set a target date for the therapy. This will help to ensure that coverage decisions are made promptly.


Know Your Rights25 A number of state governments are addressing the question of whether insurance companies ought to cover the costs associated with patients’ participation in clinical trials. Lack of such coverage is a significant barrier to many patients who might otherwise benefit from enrolling in a trial. Lack of coverage also makes it harder for researchers to successfully conduct trials that could improve prevention and treatment options. Information on State initiatives and legislation concerning cancer-related clinical trials is available at http://www.cancer.gov/ClinicalTrials/insurancelaws. By conducting your own research and learning about your rights, you may increase the likelihood that your insurance company will cover the costs of a trial.

If Your Insurance Claim Is Denied after the Trial Has Begun If a claim is denied, read your policy to find out what steps you can follow to make an appeal. In “What Cancer Survivors Need to Know about Health Insurance”, the National Coalition for Cancer Survivorship suggests that you and your doctor demonstrate to the health plan that: ·

The therapy is not just a research study, but also a valid procedure that benefits patients;

·

Your situation is similar to that of other patients who are participating in clinical trials as part of a covered benefit;

·

Possible complications have been anticipated and can be handled effectively.

You also may wish to contact your state insurance counseling hotline or insurance department for more help, or write your state insurance commissioner describing the problem. Where Else Can I Turn for Assistance? It’s never easy to deal with financial issues when you or a loved one faces cancer. Unfortunately, costs can present a significant barrier to clinical trials participation. The range of insurance issues and health plan contracts makes it impossible to deal with all of them here. You may wish to consult this partial list of publications, organizations, and Web sites for more information: 25

Adapted from Cancer.gov: http://www.cancer.gov/ClinicalTrials/insurancelaws.

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Publications What Cancer Survivors Need to Know about Health Insurance National Coalition of Cancer Survivorship 1010 Wayne Avenue, 5th floor Silver Spring, MD 20910 (301) 650-8868 http://www.cansearch.org/ Cancer Treatments Your Insurance Should Cover The Association of Community Cancer Centers 11600 Nebel Street, Suite 201 Rockville, MD 20852 (301) 984-9496 http://www.accc-cancer.org/main2001.shtml The Managed Care Answer Guide Patient Advocate Foundation 739 Thimble Shoals Boulevard, Suite 704 Newport News, VA 23606 (757) 873-6668 E-mail: [email protected] 1998 Guide to Health Insurance for People with Medicare, The Medicare Handbook Medicare Helpline: 1-800-444-4606 Health Care Financing Administration: http://www.hcfa.gov/ New Medicare site: http://www.medicare.gov/ Assistance Programs Candlelighters Childhood Cancer Foundation Ombudsman Program 910 Woodmont Avenue, #4607 Bethesda, MD 20814 (301) 657-8401; 1-800-366-2223 (toll-free) E-mail: [email protected] http://www.candlelighters.org The Ombudsman Program helps families of children with cancer and survivors of childhood cancer resolve a range of problems, including insurance coverage difficulties. Local groups appoint a Parent Advocate who works with the treatment center on behalf of families.


Medical Care Management Corporation 5272 River Road, Suite 650 Bethesda, MD 20816-1405 (301) 652-1818 email: [email protected] http://www.mcman.com/ Working for a range of clients, including health plans, employers, and patients, MCMC conducts independent, objective reviews of hightechnology medical care cases to assist in decision-making. While it does charge for its services, MCMC also offers a volunteer program for those who cannot afford to pay. More Information Resources OncoLink A service of the University of Pennsylvania Cancer Center. http://www.oncolink.com/ In addition to general cancer information, this web site features a section on financial information for patients. Among the topics: viatical settlements, life insurance, a glossary of financial and medical terms, and news about billing and insurance. American Association of Health Plans 1129 20th Street, NW, Suite 600 Washington, DC 20036-3421 (202) 778-3200 http://www.aahp.org/ The Web site section “For Consumers” includes a fact sheet on clinical research that describes various health plans’ efforts to support research initiatives and collaborate with academic health centers and universities. Health Insurance Association of America 555 13th Street, NW Washington, DC 20004 (202) 824-1600 ·

Home page: http://www.hiaa.org/

·

Consumer Information: http://www.hiaa.org/consumer/

·

Insurance Counseling Hotlines by State: http://www.hiaa.org/consumer/insurance_counsel.cfm

·

State Insurance Departments: http://www.hiaa.org/consumer/state_insurance.cfm

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Government Initiatives to Expand Insurance Coverage for Trials26 The good news is that there has been a recent effort in the U.S. to assure clinical trials coverage, with NCI involved in several new initiatives as described below: NCI-Department of Defense Agreement An innovative 1996 agreement between NCI and the Department of Defense (DoD) has given thousands of DoD cancer patients more options for care and greater access to state-of-the-art treatments. Patients who are beneficiaries of TRICARE/CHAMPUS, the DoD’s health program, are covered for NCIsponsored Phase II and Phase III clinical treatment trials. NCI and DoD are refining a system that allows physicians and patients to determine quickly what current trials meet their needs and where they are taking place. NCI-Department of Veterans Affairs Agreement A 1997 agreement with the Department of Veterans Affairs provides coverage for eligible veterans of the armed services to participate in NCIsponsored prevention, diagnosis, and treatment studies nationwide. For additional information, see the VA/DoD Beneficiaries Digest Page at http://www.va.gov/cancer.htm.

Midwest Health Plans Agreement Some NCI Cooperative Groups have reached agreements with several insurers in Wisconsin and Minnesota to provide more than 200,000 people with coverage. This coverage is allocated for patient care costs if they participate in a cooperative group-sponsored trial.

Adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=1d92be79-8748-4bda-80052a56d332463b&docid=d8092601-daf9-4794-8536-3be2712eb6b9.

26


Pediatric Cancer Care Network This network, a cooperative agreement among the Children’s Cancer Group, the Pediatric Oncology Group, and the Blue Cross Blue Shield System Association (BCBS) nationwide, will ensure that children of BCBS subscribers receive care at designated centers of cancer care excellence and may promote the enrollment of children in Cooperative Group clinical trials.

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “chronic lymphocytic leukemia” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

·

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

·

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment : Today’s Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

·

A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

·

The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

·

The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

·

Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

·

Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

·

Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna


Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antineoplastons: Substances isolated from normal human blood and urine being tested as a type of treatment for some tumors and AIDS. [NIH] Aspiration: Removal of fluid from a lump, often a cyst, with a needle and a syringe. [NIH] Bevacizumab: A monoclonal antibody that may prevent the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Carboplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] CSF: Cerebrospinal fluid. The fluid flowing around the brain and spinal cord. CSF is produced in the ventricles of the brain. [NIH] Cyclophosphamide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Cytarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

Clinical Trials 99

Decitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Etoposide: An anticancer drug that is a podophyllotoxin derivative and belongs to the family of drugs called mitotic inhibitors. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [NIH] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Homoharringtonine: An anticancer drug that belongs to the plant alkaloid family of drugs. [NIH] Idarubicin: An anticancer drug that belongs to the family of drugs called antitumor antibiotics. Also called 4-demethoxydaunorubicin. [NIH] Interferons: Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. [NIH] Intravenous: IV. Into a vein. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lymphoma: Cancer that arises in cells of the lymphatic system. [NIH] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Metaplasia: A change of cells to a form that does not normally occur in the tissue in which it is found. [NIH] Mitoxantrone: An anticancer drug that belongs to the family of drugs called antitumor antibiotics. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of


white blood cell. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

R115777: An anticancer drug that inhibits the transformation of normal cells to cancer cells. It belongs to the family of drugs called enzyme inhibitors. [NIH]

Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Sterility: 1. the inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. the state of being aseptic, or free from microorganisms. [EU] STI571: A drug that is being studied for its ability to inhibit the growth of certain cancers. It interferes with a portion of the protein produced by the bcr/abl oncogene. [NIH] Topotecan: An anticancer drug that belongs to the family drugs called topoisomerase inhibitors. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH]

101

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on chronic lymphocytic leukemia. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on chronic lymphocytic leukemia. In Part II, as in Part I, our objective is not to interpret the latest advances on chronic lymphocytic leukemia or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with chronic lymphocytic leukemia is suggested.

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CHAPTER 4. LEUKEMIA

STUDIES ON CHRONIC LYMPHOCYTIC

Overview Every year, academic studies are published on chronic lymphocytic leukemia or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on chronic lymphocytic leukemia. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on chronic lymphocytic leukemia and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and chronic lymphocytic leukemia, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where


“You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “chronic lymphocytic leukemia” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·

Low-energy Laser Therapy in Oral Mucositis Source: Journal of Oral Laser Applications. 1(2): 97-101. Autumn 2001. Contact: Available from Quintessence Publishing Co., Inc. 551 Kimberly Drive,, Carol Stream, Ill. 60188. (630) 682-3223. Website: www.quintessenz.de. Email: [email protected]. Summary: The use of high dose chemotherapy as part of the preparative regimen for stem cell transplantation is associated with mucosal damage. Laser irradiation of the oral mucosa may help to decrease the severity of mucositis. This article reports on a pilot trial that was conducted to evaluate the usefulness of low energy laser therapy in the control of pain associated with oral mucositis after stem cell transplantation or high dose chemotherapy. Eleven patients with the diagnosis of chronic myelogenous leukemia (n = 4), non-Hodgkin's lymphoma (n = 3), acute myelocytic leukemia (n = 1), and other malignancies (n = 3) were submitted to high dose chemotherapy for myeloablation. Seven patients received autologous stem cell transplantation, two patients received stem cells from allogeneic sources, and two were given high dose chemotherapy only. The oral cavity of all patients was examined by an oral medicine specialist during the pretransplant and prechemotherapy work up. The patients received irradiation with the mucolaser daily until posttransplant day 5. Mucositis was clinically evaluated according the WHO (World Health Organization) scale, and pain was measured by a visual analog scale (VAS). The laser treatment was well tolerated by the patients. Two patients had mucositis grade I or II, 8 patients had grade III to IV, and 1 patient had none. None of the patients had the maximal pain score. Six patients had grade 0 to 3, and 5 patients had grade 5 to 8 by VAS. The majority of patients associated the daily application of laser with prompt pain relief. The authors conclude that the use of low energy laser therapy may play a role in the control of pain associated with oral mucositis. 3 figures. 2 tables. 23 references.

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·

Oral Hairy Leukoplakia in a Patient with Acute Lymphocytic Leukemia Source: Oral Diseases. 5(1): 76-79. January 1999. Contact: Available from Stockton Press. Marketing Department, Houndmills, Basingstoke, Hampshire RG21 6XS, United Kingdom. (800) 747-3187. Summary: This article reports the first case of oral hairy leukoplakia (OHL) in an HIV negative 56 year old patient with acute lymphocytic leukemia (ALL). A white plaque was observed while the patient was in complete remission following chemotherapy scheme. The clinical and histopathologic findings were typical for OHL and the polymerase chain reaction method was positive for Epstein Barr virus DNA. The authors concludes that underdiagnosis and underreporting of OHL in patients with a malignant hematological disease and the apparent different environmental factors to which these non-AIDS patients have been exposed, probably constitute some of the reasons for the very few OHL cases reported in these patients. The patient, after the excisional biopsy, received prophylactic antibiotics and acyclovir and had an uneventful recovery. Careful examination of patients with a malignant hematological disease or other immunodeficiency state is suggested, in order to add knowledge to the biologic mechanisms and behavior of OHL. 3 figures. 30 references.

Federally Funded Research on Chronic Lymphocytic Leukemia The U.S. Government supports a variety of research studies relating to chronic lymphocytic leukemia and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.27 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to chronic lymphocytic leukemia and related conditions. 27 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).


For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore chronic lymphocytic leukemia and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for chronic lymphocytic leukemia: ·

Project Title: Substrates

Chronic

Myelogenous

Leukemia

and

BCR-ABL

Principal Investigator & Institution: Druker, Brian J.; Professor; Medicine; Oregon Health & Science University 3181 Sw Sam Jackson Park Rd Portland, or 97201 Timing: Fiscal Year 2000; Project Start 1-JUL-1995; Project End 0-JUN2005 Summary: (Adapted from the investigator's abstract) Chronic myelogenous leukemia (CML) is a malignancy of a pluripotent hematopoietic stem cell. The disease is characterized by the presence of a specific chromosomal translocation, t(9;22), which results in the production of a 210 kDa fusion protein termed Bcr-Abl. As compared to c-Abl, the fusion protein, Bcr-Abl, has elevated tyrosine kinase activity. Over the past 5 years, numerous substrates of the Bcr-Abl tyrosine kinase have been identified and a variety of signaling pathways have been shown to be activated in Bcr-Abl-expressing cells. However, the necessity of most of these pathways and tyrosine phosphorylated protein for BcrAbl function remain unclear. Given the complexity of Bcr-Abl, it is the applicant's belief that a combination of approaches is required to dissect Bcr-Abl function. This includes a mutagenic structure-function analysis, a biochemical analysis of protein-protein interactions, and a genetic approach. This proposal will continue the studies by Bcr-Abl function by: 1. Analyzing Bcr-Abl mutants for defects in transforming abilities in vitro and in vivo; 2. Performing biochemical analyses of Bcr-Abl kinase regulation by tyrosine phosphorylation and determining affinities of interactions with various signaling proteins, and 3. Determining the necessity of various signaling proteins for Bcr-Abl function by analyzing cell lines or mice deficient in specific proteins. Through these studies the applicant hopes to gain greater insight into the molecular mechanism of action of this activated tyrosine kinase and that this information may be applied to disorders in which activated tyrosine kinase signaling pathways have a role. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

Studies 107

·

Project Title: Dendritic Cell Therapy of Chronic Myelogenous Leukemia Principal Investigator & Institution: Litzow, Mark R.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 1-MAY-2001; Project End 0-APR2004 Summary: (Applicant's Abstract) Graft versus leukemia effect observed after allogeneic bone marrow transplant for chronic myelogenous leukemia (CML) demonstrates that CML can be recognized by the immune system. Nonetheless, the disease does not elicit a spontaneous effective immune response. The applicant postulates that CML-associated antigens do not stimulate immunity because they are not presented in the proper cellular and molecular context. He hypothesizes that ex vivo matured dendritic cells (DC) provide proper presentation of CMLassociated antigens and that such DC are effective in stimulating CMLspecific immunity in patients. In this translational project, he proposes to prime the immune response against CML by ex vivo matured reinfused autologous leukemic dendritic cells and to define methods to further enhance the effectiveness of priming and boosting the immune response. In Specific Aim 1, he will maximize expression and presentation of endogenous CML-associated antigens by mature autologous leukemic dendritic cells and stimulate a CML-specific immune response in a Phase I/II clinical trial. He will measure immunization-induced changes in CML-specific immune effector cells and correlate the changes with the status of disease; immunotherapy protocols often involve boosting with dendritic cells, yet the effects on the dynamics of T cell response are not fully understood. In Specific Aim 2, he will compare the effectiveness of cells presenting bcr-abl in the presence and in the absence of costimulatory molecules for boosting the immune response. In Specific Aim 3, he will express in dendritic cells the human IL-2 gene introduced by infection with recombinant adenovirus and test the cells for efficacy of expanding the CML-specific T cell response in vitro. The clinical study will provide information on: 1. the safety of autologous ex vivo matured dendritic cells derived from CD14-selected cells; 2. efficacy of mature leukemic dendritic cells in controlling CML, and 3. the relationship between the level of T-cell response and tumor burden in CML patients. Laboratory studies will 1) identify the cells optimal for boosting immunity in vitro and 2) maximize CML-specific T-cell responses using CML-DC genetically modified to express and secrete IL-2. The combined data will provide a comprehensive understanding of the interaction of the immune system and CML and will yield information required for the rational design of more effective clinical protocols in the future.


Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Function of GAT62 in Chronic Phase Chronic Myelogenous Leukemia Principal Investigator & Institution: Aelst, Linda V.; Sloan-Kettering Institute for Cancer Res for Cancer Research New York, Ny 10021 Timing: Fiscal Year 2000 Summary: The broad long term goal of the project is to characterize the functional role of GAT62, a protein identified as being constitutive tyrosine phosphorylated in chronic phase progenitor cells from human chronic myelogenous leukemia (CML) patients. CML is a clonal disorder of the hematopoietic stem cell characterized by the Philadelphia chromosome in which the c-abl proto-oncogene becomes linked to the bcr gene on chromosome 22, resulting in a chimeric protein termed p210 bcr/abl with deregulated tyrosine kinase activity. There is significant evidence implying that the elevated tyrosine kinase activity of bcr-abl is responsible for the proliferative and maturational abnormalities evident in the chronic phase of CML. However, the intracellular signaling cascades perturbed by bcr/abl remain to be defined. This project examines the potential role of GAT62 as mediator of p210 bcr/abl signal transduction. The specific aims are: 1) To determine whether p210 bcr/abl is the protein kinase responsible for the tyrosine phosphorylation on GAT62. 2) To map the domain(s) of GAT62 and p210 bcr/abl required for interaction. 3) To characterize the relevance of GAP-p210 bcr/abl interaction. 4) To identify and characterize proteins that associate with GAT62. 5) To define the subcellular localization of constitutive tyrosine phosphorylatd GAT62. 6) To examine the involvement of GAT62 in P210 bcr/abl mediated transformation. The project presents biochemical and molecular/cell biological approaches to study the functional role of GAT62 in CML. In vitro binding studies and phosphopeptide mapping will be performed to address whether GAT62 is a direct substrate of p210 bcr/ab1 and deletion/site directed mutagenesis will be employed for domain mapping. The importance of the GAT62/GAP interaction will be defined by performing GTPase activating protein assays, measuring the Ra-bound GDP/GTP ration and defining the subcellular localization of tyrosine phosphorylated GAT62 and GAP. The latter will be examined using two approaches, standard subcellular frationation techniques and immunochemistry. The biological relevance of GAT62 will be assessed using two assays, an in vitro assay with rat-1 fibroblasts and an in vivo assay with primary bone marrow cells. The health-relatedness of this project is that by defining the function of GAT62, as potential substrate of p210 bcr-abl, new insights may be provided into the molecular

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mechanisms underlying CML and new potential targets for therapeutic intervention by uncovered. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Initiation and Progression of Chronic Myelogenous Leukemia Principal Investigator & Institution: Canaani, Eli; Thomas Jefferson University 1020 Walnut St Philadelphia, Pa 19107 Timing: Fiscal Year 2000 Summary: There is no text on file for this abstract. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Method for Detecting Chronic Myelogenous Leukemia Cells Principal Investigator & Institution: Trnovsky, Jan; One Cell Systems, Inc. 100 Inman St, Ste 200 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 6-AUG-2002; Project End 8-FEB2003 Summary: (provided by applicant): Chronic myelogenous leukemia (CML) is characterized by a t(9;22) chromosomal translocation, which results in a fusion gene whose protein product shows enhanced tyrosine kinase activity. This fusion protein is a target in a new promising treatment using a Bcr-Abl kinase inhibitor. CML is typically detected using either slide-based fluorescence in situ hybridization (FISH) to detect the translocation, or reverse transcriptase-polymerase chain reaction (RT-PCR) to detect the fusion mRNA transcript. FISH is laborintensive and cannot easily detect rare cancer cells. RT-PCR is susceptible to contamination and false positive results. This Phase I research proposes to develop a novel assay format for detecting CML positive cells. Use of flow cytometry will permit analysis of at least a million cells per hour, and identification of rare cancer cells. Proposed Commercial Application: This assay will facilitate post-treatment patient monitoring and early detection of minimal residual disease (MRD). Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Progression of Chronic Myelogenous Leukemia Principal Investigator & Institution: Dessain, Scott K.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2000; Project Start 1-JUL-2000; Project End 0-JUN2005


Summary: (Applicant's Description): A career development award will provide the opportunity to obtain in depth training and experience in the essentials of cancer and hematology research. The proposed training involves didactic study, professional meetings, and collaborations with leaders in the fields of cancer and leukemia research. The goal of the research plan is to provide an opportunity to learn basic techniques in the study of cancer and malignant hematologic diseases, to learn to think creatively and analytically, and to develop the skills necessary to develop a successful independent research program. The combination of Dr. Robert A. Weinberg as a primary sponsor and Dr. George Q. Daley as a co-sponsor will provide outstanding mentorship. Dr. Weinberg has an established record of training outstanding investigators. Dr. Daley has a strong background in the study of human leukemias and as a clinical hematologist he provides an excellent role model of a physician-scientist. The educational opportunities and the resources that the Whitehead Institute for Biomedical Research provides are outstanding, and will complement the strong mentorship of Dr. Weinberg and Dr. Daley. The proposed research seeks to explain the clinical course of chronic myelogenous leukemia (CML). CML initially manifests as a clinically manageable chronic phase disease, characterized by a hyperproliferation of relatively normal cells. CML inevitably progresses to blast phase, a virtually u n t reatable acute leukemia. The genetic changes responsible for the progression to blast are unknown. The Weinberg laboratory has recently developed a model for cooperating oncogenes in human cells, demonstrating that primary human cells can be transformed by the combination of a viral oncogene, a ras oncogene, and the t e l o merase gene. This experimental system yields a model of human carcinogenesis that can be used to formulate a number of specific, testable hypotheses that may explain the progression of chronic phase CML to blast phase. Building on the observation that human chronic phase and blast phase cells engraft differently in the immunocompromised NOD/SCID mouse, hypotheses regarding the progression of chronic phase CML can be tested in vivo. The first two parts of the research address the role of telomerase in the natural history of CML. The second two parts explore the role of oncogenes in the pathogenesis of blast phase CML and attempt to build a multi-step model to explain the progression of chronic phase CML to blast phase. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Therapeutic Mechanisms in Chronic Myelogenous Leukemia Principal Investigator & Institution: Daley, George Q.; Whitehead Fellow; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2001; Project Start 7-MAR-2001; Project End 8-FEB2006 Summary: (Adapted from the investigator's abstract) Chronic Myelogenous Leukemia (CML) is caused by BCR/ABL, a constitutive tyrosine kinase oncoprotein. Standard chemotherapy can control leukocytosis during the initial chronic phase of CML, but does nothing to alter the inevitable development of blast crisis, an acute leukemia that ultimately proves fatal. Alpha-interferon (a-IFN) induces hematologic and cytogenetic remission, postpones blast crisis, and prolongs survival in CML patients. cx-IFN restores critical adhesion defects and stimulates active immune suppression of CML progenitors, but our knowledge of interferon mechanisms is incomplete. In preliminary studies we have uncovered roles for two interferon inducible proteins that suggest novel hypotheses to explain the therapeutic effect of interferons in CML. The Interferon Consensus Sequence Binding Protein (ICSBP), implicated in CML causation by gene knock-out in mice, inhibits BCRIABL-mediated proliferation of hematopoietic cells and sensitizes leukemia cell lines to immune rejection. We will characterize the mechanism of ICSBP-induced immunity against BCR/ABL-induced leukemia. The Interferon Inducible Protein 9-27/Leu13, an adhesion molecule that inhibits cell proliferation, was found in an array-based expression screen to be down-regulated by BCRJABL and up-regulated by ICSBP. We will investigate the lIP 927/Leul3 protein as a potentially critical point of convergence of BCRIABL and interferon signaling. Our expression screen also identified a number of novel targets of BCR/ABL action, including cyclin D2. We have demonstrated that cyclin D2-deficient mice have a profound cellintrinsic resistance to BCRJABL transformation, and we will study how cyclins D1, D2, and D3 influence the capacity of BCR/ABL to induce myeloid and lymphoid leukemia in mice. This proposal seeks to advance our fundamental knowledge of CML biology and therapeutic mechanisms in hopes of refining future treatment strategies. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: CORE--Minimal Disease Detection by PCR Principal Investigator & Institution: Arlinghaus, Ralph B.; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2000


Summary: Chronic myelogenous leukemia (CML) is a pluripotent stem cell disease, which is associated with an abnormal chromosome, termed the Philadelphia chromosome (Ph). The Ph fuses parts of the BCR and ABL genes, and the resulting Bcr-Abl oncoprotein is expressed in blood and bone marrow cells of CML patients. Two modes of therapy have been unusually effective at inducing long term remission in chronic phase CML patients: bone marrow transplantation from a matched donor and interferon-alpha treatment. Several tests are currently used to monitor treatment of CML but only the reverse transcriptase (RT) polymerase chain reaction (PCR) method is sufficiently sensitive to detect minimal residual disease. RT-PCR is known to detect as few as one cell expressing BCR-ABL in a total of about 100,000 cells. However, the standard RT-PCR method is widely used as not quantitative. Competitive quantitative PCR methods have been developed in recent years. We are adapting an approach developed by Cross and Goldman. This method involves adding known levels of BCR-ABL junction sequences, containing an insert to distinguish it from the native junction sequences, to an unknown sample and comparing the intensity of the amplimers. The reliability of the method is increased by analyzing serial patient samples from a period of time to determine whether the level of BCRABL-RNA is decreasing or increasing. For example, a pattern of decreasing level of BCR-ABL RNA would indicate a deepening remission. The aims of this grant are to adapt the Cross and Goldman method and use the test to monitor bone marrow transplant CML patients and CML patients being treated with interferon alpha. This approach will be also used in Ph+ ALL patients. The method will be established using known Bcr-Abl positive and negative cell lines; next studies will be done on cells from blood and marrow with emphasis on minimal residual disease; and the utility will be evaluated by performing a blind study with patient samples. Lastly, a core laboratory will be established for analysis blood and marrow samples of CML patient samples under study within the P01 grant by competitive PCR. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: CORE--NOD/SCID Transplantation Facility Principal Investigator & Institution: Belmont, John; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2000 Summary: The main purpose of the core unit is to provide an in vivo model for the growth of chronic myelogenous leukemia (CML) and normal stem/progenitor cells. NOD/scid animals will be used in experiments to investigate the basic biology of CML progenitors and to

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model potential therapeutic interventions. The core will breed and maintain NOD/scid mice in the Barrier Animal Facility within the Center for Comparative Medicine at Baylor College of Medicine. The facility uses strict standard operating procedures designed to keep all animals specific pathogen free (SPF). Core personnel will perform all experimental manipulations on NOD/scid mice for the individual project investigators. The core personnel will also provide in vitro manipulation of CML and normal hematopoietic progenitors. For example, the core will provide tissue culture for testing purging protocols and for retroviral vector transduction. The core personnel have special interest and expertise in retroviral vector gene marking technology and will implement serial and clone-specific gene marking techniques as required by the individual projects. The core will provide harvested bone marrow cells from transplanted NOD/scid mice and other tissues involved with leukemic disease as required by the individual investigators. The core personnel will coordinate with the flow cytometry and FISH laboratories for analysis of NOD/scid bone marrow cells and tissues. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Neurofibromatosis Type 1 Gene Regulates Myelopoiesis Principal Investigator & Institution: Clapp, David W.; Associate Professor; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 355 N Lansing Indianapolis, in 46202 Timing: Fiscal Year 2000; Project Start 1-APR-1997; Project End 1-MAR2002 Summary: The proteins encoded by the p21ras (Ras) family of protooncogenes control cellular growth and differentiation by cycling between an active guanosine triphosphate (GTP)-bound state and an inactive guanosine diphosphate (GDP)-bound state. Mammalian GTPase activating proteins (GAPs) regulate Ras proteins by accelerating GTP hydrolysis. Neurofibromin, the 327 kD protein product of the NF1 gene, contains domains that are homologous to mammalian and yeast GAPs, bind to Ras proteins with high affinity, and promotes the conversion of Ras-GTP to Ras-GDP at physiologic concentrations. Mutations in NF1 cause the common genetic disorder neurofibromatosis, type 1 (NF1) which is associated with a predisposition to neural crest derived tumors and juvenile chronic myelogenous leukemia (JCML). These observations led to the proposal that NF1 functions as a tumor suppressor gene by negatively regulating Ras-GTP. Clinical, genetic, and biochemical data from studies of hematopoietic cells strongly support this hypothesis. The Investigators have developed a murine model to investigate the role of the murine homologue of NF1 in myeloid and stem cell control. Their


laboratory has shown that hematopoietic cells from embryos that are homozygous for a targeted disruption of NF1 have a selective and enhanced sensitivity to GM-CSF in a myeloid progenitor assay that is remarkably similar to the pattern observed in patients with juvenile chronic myelogenous leukemia. Together with their collaborators, they have demonstrated that the absence of the NF1 gene in fetal liver hematopoietic cells also resulted in aberrant Ras signaling. The goals of this proposal are to investigate the cellular physiology and molecular mechanisms that underlay how NF1 regulated the proliferation and differentiation of hematopoietic progenitor and stem cell populations in vitro and in vivo. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Peptidomimetics for Inhibition of P210BCRABL--CML Principal Investigator & Institution: Austin, David J.; Assistant Professor; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2000 Summary: This proposal describes our efforts toward the synthesis of peptide mimetic molecules against chronic myelogenous leukemia (CML). In collaboration with the Deisseroth laboratory, we will target the p210/bcrabl protein kinase. Specifically, we are interested in the design of small-molecules that will specifically bind to and potentially inhibit the proliferation of myelogenous leukemia cells in vivo. Researchers on this project will synthesize a number of small-molecules, based on a generalbinding scaffold, which will be tested for binding to and inhibition of p210/bcrabl. The library proposed here has been designed on the principle of a generalbinding scaffold, and involves the random presentation of amino acid side chains, or "natural functionality", around a rigid molecular scaffold. The philosophy behind a general-binding scaffold is that nature's functionality can be radially displayed, preferable in a random and diverse fashion, to mimic both peptide and signaling molecules which may bind to and affect a protein of interest. We propose that the functionality displayed ont the molecular scaffold will have the ability to sample many local conformations,t hereby increasing the changes of identifying a small molecule inhibitor. Each of the compounds synthesized will be forwarded to the Deisseroth Laboratory for in vitro binding constants and in vivo activity. Lead compounds from these assays will then be further subjected to design and randomization in an effort to improve inhibition and gain beneficial pharmacophoric properties needed for their development as chemotherapeutic drug candidates.

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Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Chromosomes

Sequence

Based

Fish

Analysis

of

Philadelphia

Principal Investigator & Institution: Knoll, Joan H.; Children's Mercy Hospital 2401 Gillham Rd Kansas City, Mo 64108 Timing: Fiscal Year 2002; Project Start 1-APR-2002; Project End 1-MAR2004 Summary: (provided by applicant) One of the most prevalent abnormalities in leukemia patients, the Philadelphia chromosome, a translocation of the ABL1 oncogene on chromosome 9 to the BCR gene on chromosome 22, occurs in adult chronic myelogenous leukemia and childhood acute chronic leukemia. In addition to the translocation, the commercial ES-probe used in clinical cytogenetics laboratories sometimes detects deletions of DNA sequences upstream of the ABL1 gene on the derivative 9 chromosome (in 1/10 to 1/3 of patients). These deletions appear to be prognostic for early blast crisis. We hypothesize that these deletions result in hemizygosity of additional genes adjacent to ABLI. These deletion breakpoints can be refined with high- resolution fluorescence in situ studies (scFISH), which uses short single copy (sc) DNA probes designed from the draft genome sequence. Chromosomal preparations of patient specimens diagnosed with Philadelphia chromosomes in clinical cytogenetic laboratories will be analyzed with these probes. ScFISH, which has been developed in our laboratories, provides an unprecedented level of resolution for delineating sequences associated with inherited chromosomal rearrangements by FISH (Rogan, Cazcarro, Knoll, 2001; Knoll, Cazcarro, Rogan, 2000). We have developed and validated single copy DNA probes (quickly and without cloning) for FISH analysis of more than 20 distinct chromosomal regions. We aim (1) to develop scFISH probes for ABL1 oncogene, BCR and their adjacent regions from the draft genome sequence and verify their locations by FISH; (2) to compare results with scFISH probes to those obtained using the commercially available ES-probes for t(9;22) on the same patient specimens; and (3a) to categorize cytogenetically positive t(9;22) into molecular subgroups based on the sizes of deletion centromeric to ABL1 and the breakpoints within the BCR gene, (3b) to determine if there are preferential sites of breakage on chromosome 9 adjacent to ABL1, and to localize these sites. In contrast with scFISH probes, commercial reagents detecting this translocation routinely used in clinical laboratories comprise large multigenic segments. We anticipate that both the commercial and scFISH probes will detect the chromosomal translocation in some patients, however, only the scFISH probes are expected to


delineate deletions in sequences immediately adjacent to ABL 1, and to distinguish the major and minor sites of breakage in the BCR gene that correspond to chronic myelogenous leukemia and acute lymphocytic leukemia, respectively. The proposed study will delineate the chromosomal regions that undergo breakage in these types of leukemia and will establish whether there are common deletion breakage intervals on the translocated chromosome 9. Our long range goal is to classify patients based on the sites of translocation and deletion size, and then to determine if the disease complications can be attributed to the loss of specific genes adjacent to ABL1. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Signal Transduction of Type I Interferons in Malignancy Principal Investigator & Institution: Platanias, Leonidas C.; Professor of Medicine; Medicine; University of Illinois at Chicago at Chicago Chicago, Il 60612 Timing: Fiscal Year 2000; Project Start 1-MAY-1998; Project End 8-FEB2002 Summary: (adapted from the investigator's abstract) Interferon (IFNa) is used extensively in the treatment of malignancies, but the mechanisms by which it exhibits its anti-tumor effects remain largely unknown. The applicants have identified a novel IFNa-signaling pathway involving engagement of the cbl proto-oncogene product and Crk-proteins (CrkL and CrkII). The working hypothesis is that this pathway plays a critical role in IFNa-signaling by providing a link between the functional Type I IFN receptor complex and downstream cascades that mediate the antitumor effects of IFNa. The current proposal is a systematic approach that will define the molecular functions of the Cbl-Crk pathway in IFNasignaling, establish its biological relevance and determine its specific role in chronic myelogenous leukemia. Specific aim A is to identify the signaling functions of Cbl and Crk-proteins in IFNa sensitive cells. The hypothesis will be examined that Cbl, CrkL and CrkII play the role of adapter proteins, providing a link between the Type I IFN receptor and downstream pathways. This will be achieved by identifying the precise mechanisms by which IFNa-dependent tyrosine kinases regulate phosphorylation of these signaling molecules, and by identifying the elements activated downstream of them. Specific aim B is to determine the biological consequences of activation of this pathway. Two different methodologies will be used to achieve this goal. One approach will involve the generation of mutant, dominant-negative Cbl- and Crkproteins and the expression of them in IFNa-responsive cell lines. The second approach will involve studies to determine the effect of antisense

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mRNA and antisense oligonucleotides against Cbl and Crk-proteins on the biological effects of Type I IFNs on normal and malignant cells. Specific aim C is to examine the potential role of Crk-proteins in mediating the growth inhibitory effects of IFNa in chronic myelogenous leukemia. The effect of IFNa on the interaction of BCR-ABL with CrkL and on the BCR-ABL-regulated activation of mitogenic signaing pathways. Further experiments determine the sensitivity of leukemic progenitors from CML-patients to the antiproliferative effect of IFNa, and will examine whether this sensitivity correlates with specific IFNainduced signaling events. Altogether, these studies should provide valuable information the mechanisms by which signals generated at the Type I IFN receptor mediate inhibition of malignant cell proliferation. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Therapy of CML Principal Investigator & Institution: Champlin, Richard E.; Professor and Chairman; None; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2000; Project Start 1-DEC-1989; Project End 1-MAY2003 Summary: Eight projects and eight cores are proposed forming a translational research program with the goal of advancing the treatment of chronic myelogenous leukemia. Projects 1-3 involve 1) clinical investigation of novel chemo- and biologic therapies, 2) allogeneic blood and marrow transplantation focusing on enhancement of graft-versusleukemia and improving the therapeutic index of preparative regimen, and 3) Use of "leukemic" dendritic cells to generate autologous antileukemic T-cells for adoptive immunotherapy. Projects 4 and 5 are designed to improve the safety and effectiveness of allogeneic transplants for CML. The allogeneic graft-versus-leukemia effect can independently produce prolonged remissions in CML patients,b ut its efficacy is limited by the development of graft-versus-host disease. Project 4 studies the induction of GVL using lymphocytes transduced with Herpes virus thymidine kinase which renders them sensitive to the antiviral drug ganciclovir; if GVHD occurs the effectors cells can be ablated by ganciclovir treatment. In a preclinical murine model, the hypothesis that this strategy can abrogate GVHD while retaining GVL will be tested and strategies for optimally employing TK transduced donor lymphocyte infusions will be developed. Project 5 focuses on development of less toxic preparative regimens to achieve engraftment of allogeneic stem cell grafts and strategies to induce GVL without GVHD in histoincompatible recipients. Projects 6 and 7 examine the function of the bcr-abl tyrosine


kinase and molecular strategies to block its transforming effects. Project 8 examines abnormalities in DNA methylation which occur in the course of CML and their significance for therapeutic intervention. Core A is for administration. Core B provides biostatistical support for the program. Core C is for minimal disease detection using fluorescence in situ hybridization (C1) or quantitative polymerase chain reaction (C2). Core D is for cell culture assays, in vitro (D1) and in a NOD-SCID murine model (D2). Core E provides flow cytometry support and Core F is the sample collection, processing and distribution core. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

E-Journals: PubMed Central28 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).29 Access to this growing archive of e-journals is free and unrestricted.30 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “chronic lymphocytic leukemia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for chronic lymphocytic leukemia in the PubMed Central database: ·

Abnormal integrin-mediated regulation of chronic myelogenous leukemia CD34 + cell proliferation: BCR /ABL up-regulates the cyclindependent kinase inhibitor, p27Kip, which is relocated to the cell cytoplasm and incapable of regulating cdk2 activity by Yuehua Jiang, Robert C. H. Zhao, and Catherine M. Verfaillie; 2000 September 12 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27060

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Autocrine production and action of IL-3 and granulocyte colonystimulating factor in chronic myeloid leukemia by Xiaoyan Jiang, Angel Lopez, Tessa Holyoake, Allen Eaves, and Connie Eaves; 1999 October 26 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23105

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 29 With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 30 The value of PubMed Central, in addition to its role as an archive, lies the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 28

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Blast Crisis in a Murine Model of Chronic Myelogenous Leukemia by GQ Daley, RAV Etten, and D Baltimore; 1991 December 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=53129

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Calcium signaling induces acquisition of dendritic cell characteristics in chronic myelogenous leukemia myeloid progenitor cells by Friederike H. C. Engels, Gary K. Koski, Isabelle Bedrosian, Shuwen Xu, Selina Luger, Peter C. Nowell, Peter A. Cohen, and Brian J. Czerniecki; 1999 August 31 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17888

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CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia by Xiao-Feng Yang, Catherine J. Wu, Stephen McLaughlin, Antoinette Chillemi, Kathy S. Wang, Christine Canning, Edwin P. Alyea, Philip Kantoff, Robert J. Soiffer, Glenn Dranoff, and Jerome Ritz; 2001 June 19 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=34696

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Efficient Transplantation of BCR-ABL-Induced Chronic Myelogenous Leukemia- Like Syndrome in Mice by ML Gishizky, J Johnson-White, and ON Witte; 1993 April 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=46380

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Expression of Interferon Consensus Sequence Binding Protein (ICSBP) Is Downregulated in Bcr-Abl-Induced Murine Chronic Myelogenous Leukemia-Like Disease, and Forced Coexpression of ICSBP Inhibits Bcr-Abl-Induced Myeloproliferative Disorder by Sheryl X. Hao and Ruibao Ren; 2000 February 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85233

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Induction of a Chronic Myelogenous Leukemia-Like Syndrome in Mice With V-abl and BCR/ABL by MA Kelliher, J McLaughlin, ON Witte, and N Rosenberg; 1990 September 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=54594

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Molecular Relapse in Chronic Myelogenous Leukemia Patients After Bone Marrow Transplantation Detected by Polymerase Chain Reaction by CL Sawyers, L Timson, ES Kawasaki, SS Clark, ON Witte, and R Champlin; 1990 January 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=53305


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p53 in Chronic Myelogenous Leukemia in Acute Phase by E Feinstein, G Cimino, RP Gale, G Alimena, R Berthier, K Kishi, J Goldman, A Zaccaria, A Berrebi, and E Canaani; 1991 July 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=52069

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Progressive de novo DNA Methylation at the bcr-abl Locus in the Course of Chronic Myelogenous Leukemia by M Zion, D Ben-Yehuda, A Avraham, O Cohen, M Wetzler, D Melloul, and Y Ben-Neriah; 1994 October 25 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=45094

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T cells recognizing leukemic CD34 + progenitor cells mediate the antileukemic effect of donor lymphocyte infusions for relapsed chronic myeloid leukemia after allogeneic stem cell transplantation by Willem M. Smit, Marion Rijnbeek, Cornelis A. M. van Bergen, Willem E. Fibbe, Roel Willemze, and J. H. Frederik Falkenburg; 1998 August 18 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21477

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Unresponsiveness of Primitive Chronic Myeloid Leukemia Cells to Macrophage Inflammatory Protein 1[alpha], an Inhibitor of Primitive Normal Hematopoietic Cells by CJ Eaves, JD Cashman, SD Wolpe, and AC Eaves; 1993 December 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48116

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine. The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to the public.31 If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

31

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To generate your own bibliography of studies dealing with chronic lymphocytic leukemia, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “chronic lymphocytic leukemia” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “chronic lymphocytic leukemia” (hyperlinks lead to article summaries): ·

Targeted chemotherapy: chronic myelogenous leukemia as a model. Author(s): Sharifi N, Steinman RA. Source: Journal of Molecular Medicine (Berlin, Germany). 2002 April; 80(4): 219-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11976731&dopt=Abstract

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T-cell blast crisis of chronic myelogenous leukemia manifesting as a large mediastinal tumor. Author(s): Ye CC, Echeverri C, Anderson JE, Smith JL, Glassman A, Gulley ML, Claxton D, Craig FE. Source: Human Pathology. 2002 July; 33(7): 770-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12196931&dopt=Abstract

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The BCR/ABL transgene causes abnormal NK cell differentiation and can be found in circulating NK cells of advanced phase chronic myelogenous leukemia patients. Author(s): Nakajima H, Zhao R, Lund TC, Ward J, Dolan M, Hirsch B, Miller JS. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 January 15; 168(2): 643-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11777957&dopt=Abstract

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The BCR/ABL-extra signal fluorescence in situ hybridization system reliably detects deletions upstream of the ABL locus: implications for reporting of results and followup of chronic myelogenous leukemia patients. Author(s): Muller C, Hennig E, Franke C, Krahl R, Leiblein S, Niederwieser D, Deininger MW. Source: Cancer Genetics and Cytogenetics. 2002 July 15; 136(2): 149-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12237241&dopt=Abstract


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The coiled-coil domain and Tyr177 of bcr are required to induce a murine chronic myelogenous leukemia-like disease by bcr/abl. Author(s): He Y, Wertheim JA, Xu L, Miller JP, Karnell FG, Choi JK, Ren R, Pear WS. Source: Blood. 2002 April 15; 99(8): 2957-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11929787&dopt=Abstract

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Treatment of philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate. Author(s): Kantarjian HM, O'Brien S, Cortes JE, Smith TL, Rios MB, Shan J, Yang Y, Giles FJ, Thomas DA, Faderl S, Garcia-Manero G, Jeha S, Wierda W, Issa JP, Kornblau SM, Keating M, Resta D, Capdeville R, Talpaz M. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 July; 8(7): 2167-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12114417&dopt=Abstract

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Treatment options in chronic myelogenous leukemia. Author(s): Copelan EA. Source: Blood. 2002 April 15; 99(8): 3070-1; Discussion 3071. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11949629&dopt=Abstract

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Typical chronic myelogenous leukemia with e19a2 BCR/ABL transcript. Report of two cases. Author(s): Martinez-Lopez J, Ayala R, Albizua Q. Source: Haematologica. 2002 August; 87(8): Elt35. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12161380&dopt=Abstract

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A case of acute myeloid leukemia with t(7;11)(p15;p15) mimicking myeloid crisis of chronic myelogenous leukemia. Author(s): Kawakami K, Miyanishi S, Nishii K, Usui E, Murata T, Shinsato I, Shiku H. Source: International Journal of Hematology. 2002 July; 76(1): 80-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12138901&dopt=Abstract

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A case of hypoplastic chronic myelogenous leukemia initiating with pancytopenia. Author(s): Matsuda M, Miyazato H, Ueda S, Morita Y, Sakaguchi M, Tatsumi Y, Maeda Y, Kanamaru A. Source: International Journal of Hematology. 2002 April; 75(3): 335-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11999367&dopt=Abstract

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Abnormality of c-kit oncoprotein in certain patients with chronic myelogenous leukemia--potential clinical significance. Author(s): Inokuchi K, Yamaguchi H, Tarusawa M, Futaki M, Hanawa H, Tanosaki S, Dan K. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 February; 16(2): 170-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11840282&dopt=Abstract

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Acral sclerosis due to interferon-alpha-2b in chronic myelogenous leukemia. Author(s): Saydam G, Bozkurt D, Sahin F, Yuksel S, Hekimgil M, Omay SB, Buyukkececi F. Source: Acta Haematologica. 2002; 107(1): 43-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11818672&dopt=Abstract

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Activation of the c-Jun N-terminal kinase (JNK) signaling pathway is essential during PBOX-6-induced apoptosis in chronic myelogenous leukemia (CML) cells. Author(s): Mc Gee MM, Campiani G, Ramunno A, Nacci V, Lawler M, Williams DC, Zisterer DM. Source: The Journal of Biological Chemistry. 2002 May 24; 277(21): 183839. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11856743&dopt=Abstract

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Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor transplantation. Author(s): Weisdorf DJ, Anasetti C, Antin JH, Kernan NA, Kollman C, Snyder D, Petersdorf E, Nelson G, McGlave P.


Source: Blood. 2002 March 15; 99(6): 1971-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11877268&dopt=Abstract ·

Allogeneic bone marrow transplantation in children with chronic myelogenous leukemia. Author(s): Sharathkumar A, Thornley I, Saunders EF, Calderwood S, Freedman MH, Doyle J. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 MarchApril; 24(3): 215-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11990309&dopt=Abstract

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Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Author(s): Cohen MH, Williams G, Johnson JR, Duan J, Gobburu J, Rahman A, Benson K, Leighton J, Kim SK, Wood R, Rothmann M, Chen G, U KM, Staten AM, Pazdur R. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 May; 8(5): 935-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12006504&dopt=Abstract

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Arsenic trioxide induces apoptosis in chronic myelogenous leukemia K562 cells: possible involvement of p38 MAP kinase. Author(s): Shim MJ, Kim HJ, Yang SJ, Lee IS, Choi HI, Kim T. Source: J Biochem Mol Biol. 2002 July 31; 35(4): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12296996&dopt=Abstract

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Bone marrow cytogenetic complete remission achieved by interferonalpha plus cytarabine ocfosfate therapy in a patient with chronic myelogenous leukemia during extramedullary blast crisis. Author(s): Gotoh A, Miyazawa K, Uchida Y, Sashida G, Kawakubo K, Kuriyama Y, Ohyashiki K. Source: International Journal of Hematology. 2002 February; 75(2): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11939268&dopt=Abstract

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Bronchiolitis obliterans organizing pneumonia in a patient with chronic myelogenous leukemia developing after initiation of

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interferon and cytosine arabinoside. Author(s): Patel M, Ezzat W, Pauw KL, Lowsky R. Source: European Journal of Haematology. 2001 November-December; 67(5-6): 318-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11872080&dopt=Abstract ·

Busulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia. Author(s): Andersson BS, Thall PF, Madden T, Couriel D, Wang X, Tran HT, Anderlini P, de Lima M, Gajewski J, Champlin RE. Source: Biol Blood Marrow Transplant. 2002; 8(9): 477-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12374452&dopt=Abstract

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Candida arthritis in a patient with chronic myelogenous leukemia (CML) in blastic transformation, unresponsive to fluconazole, but treated effectively with liposomal amphotericin B. Author(s): Turgut B, Vural O, Demir M, Kaldir M. Source: Annals of Hematology. 2002 September; 81(9): 529-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12373355&dopt=Abstract

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Cardiac tamponade associated with imatinib mesylate therapy of chronic myelogenous leukemia. Author(s): Barton JC, Jones SC, Lamberth WC, Reymann MT, Scott VC. Source: American Journal of Hematology. 2002 October; 71(2): 139-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12353320&dopt=Abstract

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Characteristics and outcome of patients with Philadelphia chromosome negative, bcr/abl negative chronic myelogenous leukemia. Author(s): Onida F, Ball G, Kantarjian HM, Smith TL, Glassman A, Albitar M, Scappini B, Rios MB, Keating MJ, Beran M. Source: Cancer. 2002 October 15; 95(8): 1673-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12365015&dopt=Abstract

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Chronic myelogenous leukemia in chronic phase. Author(s): Kurzrock R, Kantarjian H, Talpaz M.


Source: Curr Treat Options Oncol. 2001 June; 2(3): 245-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12057124&dopt=Abstract ·

Chronic myelogenous leukemia in T cell lymphoid blastic phase achieving durable complete cytogenetic and molecular remission with imatinib mesylate (STI571; Gleevec) therapy. Author(s): Atallah E, Talpaz M, O'brien S, Rios MB, Guo JQ, Arlinghaus R, Fernandes-Reese S, Kantarjian H. Source: Cancer. 2002 June 1; 94(11): 2996-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12115389&dopt=Abstract

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Chronic myelogenous leukemia: an overview. Author(s): Tennant L. Source: Clin J Oncol Nurs. 2001 September-October; 5(5): 218-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11899767&dopt=Abstract

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Chronic myelogenous leukemia: mechanisms underlying disease progression. Author(s): Shet AS, Jahagirdar BN, Verfaillie CM. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 August; 16(8): 1402-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12145676&dopt=Abstract

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Clinical course of thrombocytopenia in patients treated with imatinib mesylate for accelerated phase chronic myelogenous leukemia. Author(s): Van Deventer HW, Hall MD, Orlowski RZ, Mitchell BS, Berkowitz LR, Hogan C, Dunphy CH, Koehler J, Shea TC. Source: American Journal of Hematology. 2002 November; 71(3): 184-190. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12410573&dopt=Abstract

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Comparison of outcome of allogeneic bone marrow transplantation with and without granulocyte colony-stimulating factor (lenograstim) donor-marrow priming in patients with chronic myelogenous leukemia. Author(s): Ji SQ, Chen HR, Wang HX, Yan HM, Pan SP, Xun CQ.

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Source: Biol Blood Marrow Transplant. 2002; 8(5): 261-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12064363&dopt=Abstract ·

Complete molecular remission in chronic myelogenous leukemia after imatinib therapy. Author(s): Barbany G, Hoglund M, Simonsson B. Source: The New England Journal of Medicine. 2002 August 15; 347(7): 539-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12181416&dopt=Abstract

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Constitutional Robertsonian translocations in (9;22)-positive chronic myelogenous leukemia. Author(s): Qian J, Xue Y, Sun J, Guo Y, Pan J, Wu Y, Wang W, Yao L. Source: Cancer Genetics and Cytogenetics. 2002 January 1; 132(1): 79-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11801317&dopt=Abstract

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Constitutive expression of SOCS3 confers resistance to IFN-alpha in chronic myelogenous leukemia cells. Author(s): Sakai I, Takeuchi K, Yamauchi H, Narumi H, Fujita S. Source: Blood. 2002 October 15; 100(8): 2926-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12351404&dopt=Abstract

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Contact with fibronectin enhances preservation of normal but not chronic myelogenous leukemia primitive hematopoietic progenitors. Author(s): Bhatia R, Williams AD, Munthe HA. Source: Experimental Hematology. 2002 April; 30(4): 324-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11937267&dopt=Abstract

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Current therapy of chronic myelogenous leukemia. Author(s): Garcia-Manero G, Talpaz M, Kantarjian HM. Source: Intern Med. 2002 April; 41(4): 254-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11993784&dopt=Abstract

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Detection of the BCR-ABL gene by interphase fluorescence in situ hybridization (iFISH) in chronic myelogenous leukemia patients after


hemopoietic stem cell transplantation: the feasibility of iFISH monitoring of therapeutic response in peripheral blood. Author(s): Lee YK, Lee DW, Kim YL, Lee S, Min CK, Kim YJ, Oh IH, Kim TG, Kim CC, Kim DW. Source: International Journal of Hematology. 2002 August; 76(2): 180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12215018&dopt=Abstract ·

Diagnosis of Chronic Myelogenous Leukemia in a Dog Using Morphologic, Cytochemical, and Flow Cytometric Techniques. Author(s): Tarrant JM, Stokol T, Blue JT, McDonough SP, Farrell P. Source: Vet Clin Pathol. 2001; 30(1): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12024326&dopt=Abstract

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Dissecting the molecular mechanism of chronic myelogenous leukemia using murine models. Author(s): Ren R. Source: Leukemia & Lymphoma. 2002 August; 43(8): 1549-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12400597&dopt=Abstract

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Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Author(s): Guglielmi C, Arcese W, Dazzi F, Brand R, Bunjes D, Verdonck LF, Schattenberg A, Kolb HJ, Ljungman P, Devergie A, Bacigalupo A, Gomez M, Michallet M, Elmaagacli A, Gratwohl A, Apperley J, Niederwieser D. Source: Blood. 2002 July 15; 100(2): 397-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12091328&dopt=Abstract

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Dose escalation of imatinib mesylate can overcome resistance to standard dose therapy in patients with chronic myelogenous leukemia. Author(s): Kantarjian HM, Talpaz M, O'Brien S, Giles F, Garcia-Manero G, Faderl S, Thomas D, Shan J, Rios MB, Cortes J. Source: Blood. 2002 September 12 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12393385&dopt=Abstract

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Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro.

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Author(s): Mow BM, Chandra J, Svingen PA, Hallgren CG, Weisberg E, Kottke TJ, Narayanan VL, Litzow MR, Griffin JD, Sausville EA, Tefferi A, Kaufmann SH. Source: Blood. 2002 January 15; 99(2): 664-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11781252&dopt=Abstract ·

Expression of the TEL/EVI1 fusion transcript in a patient with chronic myelogenous leukemia with t(3;12)(q26;p13). Author(s): Nakamura Y, Nakazato H, Sato Y, Furusawa S, Mitani K. Source: American Journal of Hematology. 2002 January; 69(1): 80-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11835339&dopt=Abstract

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Gangrene of the toes in a patient with chronic myelogenous leukemia after long-term hydroxyurea therapy. Author(s): Leo E, Kramer A, Hochhaus A, Krasniqi F, Hehlmann R, Ho AD. Source: Annals of Hematology. 2002 August; 81(8): 467-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12224005&dopt=Abstract

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Gleevec((TM)) for the Treatment of Chronic Myelogenous Leukemia: U.S. Food and Drug Administration Regulatory Mechanisms, Accelerated Approval, and Orphan Drug Status. Author(s): Cohen MH, Moses ML, Pazdur R. Source: The Oncologist. 2002 October; 7(5): 390-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12401900&dopt=Abstract

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Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. Author(s): Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, Niederwieser D, Resta D, Capdeville R, Zoellner U, Talpaz M, Druker B, Goldman J, O'Brien SG, Russell N, Fischer T, Ottmann O, Cony-Makhoul P, Facon T, Stone R, Miller C, Tallman M, Brown R, Schuster M, Loughran T, Gratwohl A, Mandelli F, Saglio G, Lazzarino M, Russo D, Baccarani M, Morra E.


Source: The New England Journal of Medicine. 2002 February 28; 346(9): 645-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11870241&dopt=Abstract ·

Hematopathologic and cytogenetic findings in imatinib mesylatetreated chronic myelogenous leukemia patients: 14 months' experience. Author(s): Braziel RM, Launder TM, Druker BJ, Olson SB, Magenis RE, Mauro MJ, Sawyers CL, Paquette RL, O'Dwyer ME. Source: Blood. 2002 July 15; 100(2): 435-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12091333&dopt=Abstract

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Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Author(s): Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB, Ottmann OG, Schiffer CA, Talpaz M, Guilhot F, Deininger MW, Fischer T, O'Brien SG, Stone RM, Gambacorti-Passerini CB, Russell NH, Reiffers JJ, Shea TC, Chapuis B, Coutre S, Tura S, Morra E, Larson RA, Saven A, Peschel C, Gratwohl A, Mandelli F, Ben-Am M, Gathmann I, Capdeville R, Paquette RL, Druker BJ. Source: Blood. 2002 May 15; 99(10): 3530-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11986204&dopt=Abstract

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Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation. Author(s): Holtz MS, Slovak ML, Zhang F, Sawyers CL, Forman SJ, Bhatia R. Source: Blood. 2002 May 15; 99(10): 3792-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11986238&dopt=Abstract

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Imatinib mesylate (STI571) therapy for Philadelphia chromosomepositive chronic myelogenous leukemia in blast phase. Author(s): Kantarjian HM, Cortes J, O'Brien S, Giles FJ, Albitar M, Rios MB, Shan J, Faderl S, Garcia-Manero G, Thomas DA, Resta D, Talpaz M.

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Source: Blood. 2002 May 15; 99(10): 3547-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11986206&dopt=Abstract ·

Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Author(s): Kantarjian HM, O'Brien S, Cortes JE, Giralt SA, Rios MB, Shan J, Giles FJ, Thomas DA, Faderl S, De Lima M, Garcia-Manero G, Champlin R, Arlinghaus R, Talpaz M. Source: Blood. 2002 September 1; 100(5): 1590-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12176876&dopt=Abstract

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Imatinib mesylate therapy in newly-diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. Author(s): Kantarjian HM, Cortes JE, O'Brien S, Giles F, Garcia-Manero G, Faderl S, Thomas D, Jeha S, Rios MB, Letvak L, Bochinski K, Arlinghaus R, Talpaz M. Source: Blood. 2002 August 29 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12393600&dopt=Abstract

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Imatinib mesylate: a new pill for chronic myelogenous leukemia. Author(s): Parmar KK, King RS. Source: Cancer Practice. 2001 September-October; 9(5): 263-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11879324&dopt=Abstract

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Immune-mediated complications during interferon alpha therapy in chronic myelogenous leukemia. Author(s): Tothova E, Kafkova A, Stecova N, Fricova M, Guman T, Svorcova E. Source: Neoplasma. 2002; 49(2): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12088112&dopt=Abstract

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Immunotherapy of relapsed resistant chronic myelogenous leukemia post allogeneic bone marrow transplantation with alloantigen pulsed donor lymphocytes. Author(s): Slavin S, Ackerstein A, Morecki S, Gelfand Y, Cividalli G.


Source: Bone Marrow Transplantation. 2001 October; 28(8): 795-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11781634&dopt=Abstract ·

In vitro effects of STI 571-containing drug combinations on the growth of Philadelphia-positive chronic myelogenous leukemia cells. Author(s): Scappini B, Onida F, Kantarjian HM, Dong L, Verstovsek S, Keating MJ, Beran M. Source: Cancer. 2002 May 15; 94(10): 2653-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12173333&dopt=Abstract

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In vitro studies of the combination of imatinib mesylate (Gleevec) and arsenic trioxide (Trisenox) in chronic myelogenous leukemia. Author(s): La Rosee P, Johnson K, O'Dwyer ME, Druker BJ. Source: Experimental Hematology. 2002 July; 30(7): 729-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12135670&dopt=Abstract

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Insights from pre-clinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec) in chronic myelogenous leukemia: a translational perspective. Author(s): La Rosee P, O'Dwyer ME, Druker BJ. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 July; 16(7): 1213-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12094245&dopt=Abstract

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Isolated cavernous sinus extramedullary relapse of chronic myelogenous leukemia following allogeneic stem cell transplant. Author(s): Martel L, Reddy K, Greco M, Tuscano M, Richman M, Wun T. Source: Annals of Hematology. 2002 February; 81(2): 108-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11907793&dopt=Abstract

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Long-term follow-up of allogeneic bone marrow transplantation after reduced-intensity conditioning in patients with chronic myelogenous leukemia in the chronic phase. Author(s): Okamoto S, Watanabe R, Takahashi S, Mori T, Izeki T, Nagayama H, Ishida A, Takayama N, Yokoyama K, Tojo A, Asano S, Ikeda Y.

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Source: International Journal of Hematology. 2002 June; 75(5): 493-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12095149&dopt=Abstract ·

Lymphoid preponderance and the absence of basophilia and splenomegaly are frequent in m-bcr-positive chronic myelogenous leukemia. Author(s): Hur M, Song EY, Kang SH, Shin DH, Kim JY, Park SS, Cho HI. Source: Annals of Hematology. 2002 April; 81(4): 219-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11976825&dopt=Abstract

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Mixed chimerism of bone marrow CD34+ progenitor cells (genotyping, bcr/abl analysis) after allogeneic transplantation for chronic myelogenous leukemia. Author(s): Thiele J, Wickenhauser C, Kvasnicka HM, Varus E, Kleppe S, Beelen DW, Schaefer UW. Source: Transplantation. 2002 October 15; 74(7): 982-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12394842&dopt=Abstract

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Multiple sclerosis associated with interferon-alpha therapy for chronic myelogenous leukemia. Author(s): Kataoka I, Shinagawa K, Shiro Y, Okamoto S, Watanabe R, Mori T, Ito D, Harada M. Source: American Journal of Hematology. 2002 June; 70(2): 149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12111789&dopt=Abstract

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Parkinsonism associated with interferon alpha therapy for chronic myelogenous leukemia. Author(s): Sarasombath P, Sumida K, Kaku DA. Source: Hawaii Med J. 2002 March; 61(3): 48, 57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11965836&dopt=Abstract

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Peptides spanning the fusion region of Abl/Bcr are immunogenic and sensitize CD8(+) T lymphocytes to recognize native chronic myelogenous leukemia. Author(s): Wagner WM, Ouyang Q, Pawelec G.


Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 November; 16(11): 2341-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12399986&dopt=Abstract ·

Posttransplantation Epstein-Barr viral meningitis in a patient with chronic myelogenous leukemia. Author(s): Kanamori H, Fujisawa S, Yamaji S, Tanaka M, Tomita N, Fujimaki K, Ishigatsubo Y. Source: International Journal of Hematology. 2001 December; 74(4): 473-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11794708&dopt=Abstract

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Progress with chronic myelogenous leukemia: a personal perspective over four decades. Author(s): Nowell PC. Source: Annual Review of Medicine. 2002; 53: 1-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11818460&dopt=Abstract

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Purging of chronic myelogenous leukemia cells by retrovirally expressed anti-bcr-abl ribozymes with specific cellular compartmentalization. Author(s): Mendoza-Maldonado R, Zentilin L, Fanin R, Giacca M. Source: Cancer Gene Therapy. 2002 January; 9(1): 71-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11916246&dopt=Abstract

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Recent advancements in the treatment of chronic myelogenous leukemia. Author(s): O'Dwyer ME, Mauro MJ, Druker BJ. Source: Annual Review of Medicine. 2002; 53: 369-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11818480&dopt=Abstract

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Resolution of psoriasis following allogeneic bone marrow transplantation for chronic myelogenous leukemia: case report and review of the literature. Author(s): Kanamori H, Tanaka M, Kawaguchi H, Yamaji S, Fujimaki K, Tomita N, Fujisawa S, Ishigatsubo Y.

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Source: American Journal of Hematology. 2002 September; 71(1): 41-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12221673&dopt=Abstract ·

Results of a phase II trial of a combination of oral cytarabine ocfosfate (YNK01) and interferon alpha-2b for the treatment of chronic myelogenous leukemia patients in chronic phase. Author(s): Maloisel F, Guerci A, Guyotat D, Ifrah N, Michallet M, Reiffers J, Tertain G, Blanc M, Bauduer F, Briere J, Abgrall JF, Pegourie-Bandelier B, Solary E, Cambier N, Coso D, Vilque JP, Delain M, Harousseau JL, Rousselot P, Belhadj K, Morice P, Attal J, Chabin M, Chastang C, Guilhot J, Guilhot F. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 April; 16(4): 573-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11960335&dopt=Abstract

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Results of an allogeneic non-myeloablative stem cell transplantation program in patients with chronic myelogenous leukemia. Author(s): Ruiz-Arguelles GJ, Gomez-Almaguer D, Lopez-Martinez B, Cantu-Rodriguez OG, Jaime-Perez JC, Gonzalez-Llano O. Source: Haematologica. 2002 August; 87(8): 894-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12161373&dopt=Abstract

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Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral blood stem cell transplantation (PBSCT). Author(s): Fischer T, Reifenrath C, Hess GR, Corsetti MT, Kreil S, Beck J, Meinhardt P, Beltrami G, Schuch B, Gschaidmeier H, Hehlmann R, Hochhaus A, Carella A, Huber C. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 July; 16(7): 1220-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12094246&dopt=Abstract

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Severe tumor lysis syndrome during treatment with STI 571 in a patient with chronic myelogenous leukemia accelerated phase. Author(s): Vora A, Bhutani M, Sharma A, Raina V.


Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 November; 13(11): 1833-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12419759&dopt=Abstract ·

Signaling via the interferon-alpha receptor in chronic myelogenous leukemia cells. Author(s): Verma A, Platanias LC. Source: Leukemia & Lymphoma. 2002 April; 43(4): 703-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12153154&dopt=Abstract

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Treatment of blastic phase chronic myeloid leukemia with mitoxantrone, cytosine arabinoside and high dose methylprednisolone. Author(s): Bolaman Z, Koseoglu M, Ayyildiz O, Kadikoylu G, Sonmez HM, Demir S, Muftuoglu E. Source: Haematologia. 2002; 32(1): 49-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12243555&dopt=Abstract

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Accelerated and blastic phase of chronic myeloid leukemia. Author(s): Dutcher JP, Wiernik PH. Source: Curr Treat Options Oncol. 2000 April; 1(1): 51-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12057061&dopt=Abstract

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An epidemiologic study to screen for chronic myelocytic leukemia in war victims exposed to mustard gas. Author(s): Ghanei M, Vosoghi AA. Source: Environmental Health Perspectives. 2002 May; 110(5): 519-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12003756&dopt=Abstract

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Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop. Author(s): Roumiantsev S, Shah NP, Gorre ME, Nicoll J, Brasher BB, Sawyers CL, Van Etten RA.

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Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 August 6; 99(16): 10700-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12149456&dopt=Abstract ·

Coexistence of chronic myeloid leukemia and hairy cell leukemia of common clonal origin. Author(s): Pajor L, Kereskai L, Tamaska P, Vass JA, Radvanyi G. Source: Cancer Genetics and Cytogenetics. 2002 April 15; 134(2): 114-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12034522&dopt=Abstract

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Coexistence of Philadelphia-positive chronic granulocytic leukemia and diffuse large B-cell lymphoma at initial diagnosis. Author(s): Zamecnikova A, Vranovsky A, Hlavcak P. Source: Leukemia & Lymphoma. 2002 February; 43(2): 429-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11999582&dopt=Abstract

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Cutaneous lesions and chronic myelocytic leukemia (CML) in progression. Author(s): Paydas S. Source: Annals of Hematology. 2002 March; 81(3): 178. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11904748&dopt=Abstract

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Cyclosporine inhibition of P-glycoprotein in chronic myeloid leukemia blast phase. Author(s): List AF, Kopecky KJ, Willman CL, Head DR, Slovak ML, Douer D, Dakhil SR, Appelbaum FR. Source: Blood. 2002 September 1; 100(5): 1910-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12176916&dopt=Abstract

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Derivative chromosome 9 deletions in chronic myeloid leukemia: poor prognosis is not associated with loss of ABL-BCR expression, elevated BCR-ABL levels, or karyotypic instability. Author(s): Huntly BJ, Bench AJ, Delabesse E, Reid AG, Li J, Scott MA, Campbell L, Byrne J, Pinto E, Brizard A, Niedermeiser D, Nacheva EP, Guilhot F, Deininger M, Green AR.


Source: Blood. 2002 June 15; 99(12): 4547-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12036887&dopt=Abstract ·

Effect of interferon-alpha(2a) on neutrophil adhesion and phagocytosis in chronic myeloid leukemia and Behcet's disease. Author(s): Karti SS, Ovali E, Ratip S, Cetiner M, Direskeneli H, Bayik M, Akoglu T. Source: Clinical Rheumatology. 2002 June; 21(3): 211-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12111626&dopt=Abstract

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Efficacy of the farnesyl transferase inhibitor, ZARNESTRATM (R115777), in chronic myeloid leukemia and other other hematological malignancies. Author(s): Cortes JE, Albitar M, Thomas D, Giles F, Kurzrock R, Thibault A, Rackoff W, Koller C, O'Brien S, Garcia-Manero G, Talpaz M, Kantarjian H. Source: Blood. 2002 October 31 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12411300&dopt=Abstract

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Enrichment of normal progenitors in counter-flow centrifugal elutriation (CCE) fractions of fresh chronic myeloid leukemia leukapheresis products. Author(s): Dlubek D, Dybko J, Wysoczanska B, Laba A, Klimczak A, Kryczek I, Konopka L, Lange A. Source: European Journal of Haematology. 2002 May; 68(5): 281-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12144534&dopt=Abstract

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Expression of NK-associated antigens in extramedullary lymph nodal blast crisis of chronic myeloid leukemia on fine-needle cytology. Author(s): Zeppa P, Marino G, Picardi M, Luciano L, Vetrani A, Palombini L. Source: Diagnostic Cytopathology. 2002 September; 27(3): 158-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12203863&dopt=Abstract

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Idiopathic intracranial hypertension as the initial manifestation of chronic myeloid leukemia: letter to editor. Author(s): Pavithran K, Thomas M.

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Source: Neurology India. 2002 June; 50(2): 230. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12134204&dopt=Abstract ·

Imatinib mesylate-induced hepato-toxicity in chronic myeloid leukemia demonstrated focal necrosis resembling acute viral hepatitis. Author(s): Ohyashiki K, Kuriyama Y, Nakajima A, Tauchi T, Ito Y, Miyazawa H, Kimura Y, Serizawa H, Ebihara Y. Source: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 October; 16(10): 2160-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12357373&dopt=Abstract

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Management of the chronic leukemias: special considerations in the elderly patient. Part III rarer chronic myeloid leukemias. Author(s): Spiers AS. Source: Hematology (Amsterdam, Netherlands). 2002 February; 7(1): 1-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12171771&dopt=Abstract

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Molecular cytogenetic characterization of a complex rearrangement involving chromosomes 9 and 22 in a case of Ph-negative chronic myeloid leukemia. Author(s): Storlazzi CT, Anelli L, Surace C, Lonoce A, Zagaria A, Nanni M, Curzi P, Rocchi M. Source: Cancer Genetics and Cytogenetics. 2002 July 15; 136(2): 141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12237239&dopt=Abstract

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Molecular cytogenetic characterization of a novel additional chromosomal aberration in blast crisis of a Ph-positive chronic myeloid leukemia. Author(s): Storlazzi CT, Anelli L, Surace C, Rocchi M, Albano F, Pastore D, Liso V, Specchia G. Source: Cancer Genetics and Cytogenetics. 2002 April 15; 134(2): 109-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12034521&dopt=Abstract

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Multicolor COBRA-FISH analysis of chronic myeloid leukemia reveals novel cryptic balanced translocations during disease progression.


Author(s): Barbouti A, Johansson B, Hoglund M, Mauritzson N, Strombeck B, Nilsson PG, Tanke HJ, Hagemeijer A, Mitelman F, Fioretos T. Source: Genes, Chromosomes & Cancer. 2002 October; 35(2): 127-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12203776&dopt=Abstract ·

Neutrophilic-chronic myeloid leukemia: low levels of p230 BCR/ABL mRNA and undetectable BCR/ABL protein may predict an indolent course. Author(s): Verstovsek S, Lin H, Kantarjian H, Saglio G, De Micheli D, Pane F, Garcia-Manero G, Intrieri M, Rotoli B, Salvatore F, Guo JQ, Talpaz M, Specchia G, Pizzolo G, Liberati AM, Cortes J, Quackenbush RC, Arlinghaus RB. Source: Cancer. 2002 May 1; 94(9): 2416-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12015767&dopt=Abstract

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Relationship of the BCR gene breakpoint and the type of BCR/ABL transcript to clinical course, prognostic indexes and survival in patients with chronic myeloid leukemia. Author(s): Prejzner W. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 May; 8(5): Br193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12011769&dopt=Abstract

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Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. Author(s): Roche-Lestienne C, Soenen-Cornu V, Grardel-Duflos N, Lai JL, Philippe N, Facon T, Fenaux P, Preudhomme C. Source: Blood. 2002 August 1; 100(3): 1014-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12130516&dopt=Abstract

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Significance of cytogenetic and fluorescence in situ hybridization analysis in evaluating antichronic myeloid leukemia efficacy of different immune effector cells. Author(s): Tong CR, Hong B, Qiu JY, Chen Z, Lu DP.

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Source: Cancer Genetics and Cytogenetics. 2002 April 1; 134(1): 21-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11996791&dopt=Abstract ·

Spectral karyotyping refined the identification of a der(Y)t(Y;1)(q11.1 or.2;q12) in the blast cells of a patient with atypical chronic myeloid leukemia. Author(s): Ohsaka A, Hisa T. Source: Acta Haematologica. 2002; 107(4): 224-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12053151&dopt=Abstract

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Successful major surgical recovery of a patient following haploidentical stem cell transplantation for chronic myeloid leukemia in blast crisis and aspergillosis. Author(s): Varadi G, Svirsky O, Nagler A. Source: Acta Haematologica. 2002; 108(1): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12145464&dopt=Abstract

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Successful treatment of chronic myeloid leukemia during pregnancy with hydroxyurea. Author(s): Fadilah SA, Ahmad-Zailani H, Soon-Keng C, Norlaila M. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 June; 16(6): 1202-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12040456&dopt=Abstract

Vocabulary Builder Aberrant: Wandering or deviating from the usual or normal course. [EU] Acyclovir: An antiviral agent used to prevent or treat cytomegalovirus and herpes simplex infections that may occur when the body is immunosuppressed. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Analog:

In chemistry, a substance that is similar, but not identical, to


another. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH] Antigens: Substances that cause the immune system to make a specific immune response. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Apoptosis: A normal series of events in a cell that leads to its death. [NIH] Aspergillosis: An infectious fungal disease that occurs most often in the skin, ears, nasal sinuses, and lungs of people with suppressed immune systems. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Dendritic: 1. branched like a tree. 2. pertaining to or possessing dendrites. [EU]

Embryo: Having to do with an early stage in the development of a plant or an animal. In vertebrate animals, this stage lasts from shortly after fertilization until all major body parts appear. In particular, in humans, this stage lasts from about 2 weeks after fertilization until the end of the seventh or eighth week of pregnancy. [NIH]

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Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Ganciclovir: An antiviral agent used to prevent or treat cytomegalovirus infections that may occur when the body's immune system is suppressed. In gene therapy, ganciclovir is used with an altered herpes simplex virus-1 gene to kill advanced melanoma cells and brain tumor cells. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] GVHD: Graft-versus-host disease. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Hematologist: A doctor who specializes in treating diseases of the blood. [NIH]

Hepatitis: Inflammation of the liver. [NIH] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] HIV: Human immunodeficiency virus, immunodeficiency syndrome (AIDS). [NIH]

the

cause

of

acquired

Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Humoral: Of, relating to, proceeding from, or involving a bodily humour now often used of endocrine factors as opposed to neural or somatic. [EU] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrolysis: A chemical reaction that uses water to break down a compound. [NIH]


Hypertension: Abnormally high blood pressure. [NIH] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [EU] Immunization: The induction of immunity. [EU] Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunology: The study of the body's immune system. [NIH] Indolent: A type of cancer that grows slowly. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Intracellular: Inside a cell. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Lesion: An area of abnormal tissue change. [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease

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in a specific location or site. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Methylprednisolone: A corticosteroid hormone replacement. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH]

Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Necrosis: Refers to the death of living tissues. [NIH] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma:

Cancer that arises in immature nerve cells and affects


mostly infants and children. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neutrophil: A type of white blood cell. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Pancytopenia: Deficiency of all cell elements of the blood; aplastic anaemia. [EU]

Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Phagocytosis: Endocytosis of particulate material, such as microorganisms or cell fragments. The material is taken into the cell in membrane-bound vesicles (phagosomes) that originate as pinched off invaginations of the plasma membrane. Phagosomes fuse with lysosomes, forming phagolysosomes in which the engulfed material is killed and digested. [EU] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH] Pneumonia: An inflammatory infection that occurs in the lung. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH]

Psoriasis: A chronic disease of the skin marked by red patches covered with white scales. [NIH] Radiotherapy: The treatment of disease by ionizing radiation. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used

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chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] SPF: Sun protection factor, scale for rating the level of sunburn protection in sunscreen products. The higher the SPF, the more sunburn protection it provides. Sunscreens with an SPF value of 2 through 11 provide minimal protection against sunburns. Sunscreens with an SPF of 12 through 29 provide moderate protection, which is adequate for most people. Those with an SPF of 30 or higher provide high protection against sunburn and are sometimes recommended for people who are highly sensitive to the sun. [NIH] Splenomegaly: Enlargement of the spleen. [EU] Substrate: A substance upon which an enzyme acts. [EU] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Thrombocytopenia: A decrease in the number of platelets in the blood that may result in easy bruising and excessive bleeding from wounds or bleeding in mucous membranes and other tissues. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH]

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CHAPTER 5. PATENTS ON CHRONIC LYMPHOCYTIC LEUKEMIA Overview You can learn about innovations relating to chronic lymphocytic leukemia by reading recent patents and patent applications. Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.32 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available to patients with chronic lymphocytic leukemia within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available to patients with chronic lymphocytic leukemia. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information.

32Adapted

from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.


Patents on Chronic Lymphocytic Leukemia By performing a patent search focusing on chronic lymphocytic leukemia, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on chronic lymphocytic leukemia: ·

Human gene/protein involved in chronic myelogenous leukemia Inventor(s): Carpino; Nicholas A. (Memphis, TN), Kobayashi; Ryuji (Syosset, NY), Wisniewski; David G. (Staten Island, NY), Strife; Annabel O'C. (New York, NY), Clarkson; Bayard D. (New York, NY) Assignee(s): Cold Spring Harbor Laboratory (Cold Spring Harbor, NY), Sloan-Kettering Institute for Cancer Research (New York, NY) Patent Number: 6,100,386 Date filed: January 22, 1997 Abstract: Characteristic of chronic myelogenous leukemia (CML) is the presence of the chimeric p120.sup.bcr-abl protein possessing elevated protein tyrosine kinase activity relative to normal c-abl tyrosine kinase. Hematopoietic progenitors isolated from CML patients in the chronic phase contain a constitutively tyrosine phosphorylated protein that migrates at approximately 62 kDa by SDS-PAGE and associates with the p120 ras GTPase-activating protein (GAP). This novel protein, called p62.sup.dok (p62 protein downstream of tyrosine kinases), was isolated from a hematopoietic cell line expressing p120.sup.bcr-abl. Association of p62.sup.dok with GAP correlates with its tyrosine phosphorylation. p62.sup.dok is rapidly tyrosine phosphorylated upon activation of the ckit receptor, implicating it as a component of a signal transduction pathway downstream of receptor tyrosine kinases. Excerpt(s): Chronic myelogenous leukemia (CML) is a disease having clinical and pathological features distinct from those of other forms of leukemia. It is widely accepted that the cause of CML is a specific chromosomal translocation between human chromosome 9 and human chromosome 22. The N chromosome resulting from this translocation is commonly referred to as the Philadelphia chromosome. Darnell, J. et al.,

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Molecular Cell Biology, 2nd Ed., W. H. Freeman and Co., New York (1990), p. 992. The gene for c-abl (ABL), a tyrosine kinase thought to be involved in growth control, resides on the distal arm of human chromosome 9, while the gene for c-bcr (BCR) resides on human chromosome 22. The translocation places the promoter distal three exons of ABL, including those elements which encode the tyrosine kinase domain, downstream of either the first or second exon of BCR. Chung, S. and Wong, P. M. C., Oncogene, 10:1261-1268 (1995). The product of the translocation between human chromosome 9 and human chromosome 22 is a chimeric gene, BCR-ABL, which encodes a fusion protein, often referred to as p185.sup.bcr-abl or p210.sup.bcr-abl, depending upon the inclusion of the second exon of BCR. Bartram, C. R., et al., Nature, 306:277-280 (1983). p185.sup.bcr-abl causes acute leukemia, typically lymphoblastic; p210.sup.bcr-abl usually causes CML, but can occasionally also cause acute leukemia. ... Following this chromosomal translocation within a single, primitive myeloid stem cell, the progeny of the affected cell gradually populate the entire intermediate and late hematopoietic maturational compartments. Despite the presence of the Philadelphia chromosome, these progeny, referred to as Ph.sup.+ cells, are able to differentiate and mature along the various myeloid lineages while retaining the capacity to function as their normal, unaffected counterparts. Invariably, in an average span of three to five years, the disease progresses into a malignant stage known as blast crisis. The affected cells acquire additional chromosomal abnormalities and lose their ability to differentiate and mature, resulting in the functional breakdown of the hematopoietic system. Clarkson, B. and Strife, A., Leukemia, 7:1683-1721 (1993). Daley, G. Q. and Ben Neriah, Y., Adv. Cancer Res., 57:151-184 (1991). Deisseroth, A. B. and Arlinghaus, R. B., eds. Chronic Myelogenous Leukemia-Molecular Approaches to Research and Therapy, New York, Marcel Dekker (1991). Sawyers, C. L. et al., Cell, 64:337-350 (1991). Web site: http://www.delphion.com/details?pn=US06100386__ ·

Therapeutic treatment of chronic myelogenous administration of 2-chloro-2'-deoxy adenosine Inventor(s): Beutler; Ernest (La Jolla, CA) Assignee(s): The Scripps Research Institute (La Jolla, CA) Patent Number: 5,401,724 Date filed: February 25, 1994

leukemia

by


Abstract: A process for the treatment of chronic myelogenous leukemia in mammals is disclosed that utilizes a 2-halo-2'-deoxyadenosine derivative as the active treating agent. Excerpt(s): This invention relates to a novel treatment for chronic myelogenous leukemia. More particularly, this invention relates to a process for the treatment of chronic myelogenous leukemia involving the administration of a 2-halo-2'-deoxyadenosine. ... Chronic myelogenous leukemia (CML), also known as chronic granulocytic leukemia (CGL), is a neoplastic disorder of the hematopoietic stem cell. In its early phases it is characterized by leukocytosis, the presence of increased numbers of immature granulocytes in the peripheral blood, splenomegaly and anemia. These immature granulocytes include basophils, eosinophils, and neutrophils. The immature granulocytes also accumulate in the bone marrow, spleen, liver, and occasionally in other tissues. Patients presenting with this disease characteristically have more than 75,000 white blood cells per microliter (.mu.l), and the count may exceed 500,000/.mu.l. ... Although busulfan and hydroxyurea can be effective in treating chronic myelogenous leukemia, the bone marrow of treated patients still contains a predominance of cells with the translocation. In contrast, the marrow of patients treated with .alpha.-interferon sometimes loses the clone with the translocation. This result suggests that .alpha.-interferon may alter the natural course of the disease. There is, as yet, no evidence that this is the case. Web site: http://www.delphion.com/details?pn=US05401724__ ·

Carbohydrate specific to chronic myelogenous leukemia granulocytes Inventor(s): Fukuda; Minoru (San Diego, CA), Fukuda; Michiko (San Diego, CA) Assignee(s): La Jolla Cancer Research Foundation (La Jolla, CA) Patent Number: 4,939,083 Date filed: October 30, 1986 Abstract: A substantially purified carbohydrate is provided which is isolated from chronic myelogenous leukemia cells. The carbohydrate is immunogenic and can be utilized to raise both polyclonal and monoclonal antibodies. Excerpt(s): The present invention provides a novel carbohydrate which is advantageously used as a marker for chronic myelogenous leukemia. This novel carbohydrate will be hereinafter termed "CML-G2." Because this novel carbohydrate, CML-G2, is apparently absent in normal

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granulocytes and acute myelogenous leukemia cells, it is a specific marker for CML cells. Moreover, CML-G2 is immunogenic and can therefore be used to produce antibodies which recognize and specifically bind this novel carbohydrate. In another aspect of the invention, antibodies specific to CML-G2 are utilized, for example, in diagnosis and therapy. Such antibodies are produced either polyclonally or monoclonally. Alternatively, other carbohydrate binding proteins, such as lectins, which bind specifically to CML-G2 structure may be used in the same manner as monoclonal antibodies. Web site: http://www.delphion.com/details?pn=US04939083__ ·

Synthetic oligonucleotides useful in diagnosis of chronic myelogenous leukemia Inventor(s): Rossi; John J. (Glendora, CA) Assignee(s): City of Hope (Duarte, CA) Patent Number: 4,874,853 Date filed: April 18, 1988 Abstract: Synthetic oligonucleotide for detection of the bcr-abl RNA from blood or bone marrow of patients with chronic myelogenous leukemia. Excerpt(s): Chronic myelogenous leukemia is characterized by a reciprocal translocation between chromosomes 9 and 22 of man. This results in an abbreviated chromosome 22 termed the Philadelphia chromosome which is found in over 95 percent of patients with chronic myelogenous leukemia and in a minority of patients with acute lymphoblastic leukemia. In this translocation, the abl gene from chromosome 9 is spliced to a region on chromosome 22 called the breakpoint cluster region (bcr). This fusion gene, bcr-abl, is transcribed into a unique RNA transcript that is about 8 kb in size. ... This invention pertains to primers and probes which can detect the bcr-abl RNA from blood or bone marrow of patients with chronic myelogenous leukemia. The patient's RNA is amplified using unique primers homologous to flanking sequences to the bcr-abl splice sites. Oligonucleotide probes complementary to the two most common bcr-abl splice sequences are then used to detect the amplified DNA. The assay is useful to detect residual or relapsed chronic myelogenous leukemia and to distinguish between Philadelphia chromosome positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myelogenous leukemia. Web site: http://www.delphion.com/details?pn=US04874853__


·

Method and composition for detection of human chronic myelogenous leukemia Inventor(s): Witte; Owen N. (Santa Monica, CA), Watanabe; Susan (Santa Monica, CA), Konopka; James (Santa Monica, CA) Assignee(s): The Regents of the University of California (Berkeley, CA) Patent Number: 4,599,305 Date filed: July 16, 1984 Abstract: A method for detecting chronic myelogenous leukemia in a human comprising the step of testing a biological sample from a patient to determine the presence of a marker protein (P210) which is characterized as a c-abl protein having tyrosine kinase activity and a molecular weight of approximately 210,000. Antisera which are specific for the P210 protein are disclosed which can be used to precipitate the P210 protein to allow identification by gel electrophoresis or other technique. Excerpt(s): The present invention relates generally to methods and reagents used in the detection of cancer. More particularly, the present invention relates to a new diagnostic approach for the detection of chronic myelogenous leukemia. ... In accordance with the present invention, a method is provided for detecting chronic myelogenous leukemia which is simple, accurate and quick. The present invention is based upon the discovery that the c-abl protein normally found in humans is present in an altered state in individuals having chronic myelogenous leukemia. The altered c-abl protein exhibits tyrosine kinase activity which is not present in normal human c-abl protein and further has a molecular weight of approximately 210,000 which is much higher than the normal c-abl molecular weight of 150,000. ... The method for detecting chronic myelogenous leukemia in humans in accordance with the present invention involves testing a biological sample from the patient to determine whether or not the above referenced marker protein is present. Any number of immunoprecipitation/gel electrophoresis methods along with radioimmunoassay, immunofluorescence, immunoperoxidase and other assays may be utilized in determining the presence of the marker protein. Web site: http://www.delphion.com/details?pn=US04599305__

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Patent Applications on Chronic Lymphocytic Leukemia As of December 2000, U.S. patent applications are open to public viewing.33 Applications are patent requests which have yet to be granted (the process to achieve a patent can take several years).

Keeping Current In order to stay informed about patents and patent applications dealing with chronic lymphocytic leukemia, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “chronic lymphocytic leukemia” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on chronic lymphocytic leukemia. You can also use this procedure to view pending patent applications concerning chronic lymphocytic leukemia. Simply go back to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and 33

This has been a common practice outside the United States prior to December 2000.


heterosaccharides. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Lectins: Protein or glycoprotein substances, usually of plant origin, that bind to sugar moieties in cell walls or membranes and thereby change the physiology of the membrane to cause agglutination, mitosis, or other biochemical changes in the cell. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH]

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CHAPTER 6. LEUKEMIA

BOOKS

ON

CHRONIC

LYMPHOCYTIC

Overview This chapter provides bibliographic book references relating to chronic lymphocytic leukemia. You have many options to locate books on chronic lymphocytic leukemia. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on chronic lymphocytic leukemia include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is available for loan.

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “chronic lymphocytic leukemia” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or


relevance. The following was recently catalogued by the National Library of Medicine:34 ·

Acute myelogenous leukemia: progress and controversies: proceedings of a Wyeth-Ayerst-UCLA Symposia Western Workshop held at Lake Lanier, Georgia, November 28-December 1, 1989. Author: editor, Robert Peter Gale; Year: 1990; New York: Wiley-Liss, c1990. ISBN: 0471568724 http://www.amazon.com/exec/obidos/ASIN/0471568724/icongroupin terna

·

Acute myelogenous leukemia in childhood: implications of therapy studies for future risk-adapted treatment strategies. Author: U. Creutzig, J. Ritter, G. Schellong (eds.); Year: 1990; Berlin; New York: Springer-Verlag, c1990. ISBN: 3540520708 http://www.amazon.com/exec/obidos/ASIN/3540520708/icongroupin terna

·

Advances in chronic lymphocytic leukemia: proceedings from the 5th International Workshop on Chronic Lymphocytic Leukemia, Sitges (Barcelona), Spain, April 1991. Author: edited by Aaron Polliack and Emilio Montserrat; Year: 1991; Chur; Philadelphia: Harwood Academic Publishers, c1991. ISBN: 3718652137 http://www.amazon.com/exec/obidos/ASIN/3718652137/icongroupin terna

·

Alpha interferon in the treatment of chronic myeloid leukaemia. Author: A. Smithies; Year: 1996; Bristol, England: U.K. National Health Service, South and West Regional Health Authority, 1996.

·

Apprentice to Paracelsus: my search for the secrets of healing. Author: by Kenneth J. Dillon; Year: 1994; McLean, Va.: McLean Research Associates, c1994. ISBN: 0964297647 http://www.amazon.com/exec/obidos/ASIN/0964297647/icongroupin terna

·

B1 lymphocytes in B cell neoplasia: 16th Workshop on the Mechanisms of B Cell Neoplasia, 1999. Author: edited by M. Potter and F. Melchers; Year: 2000; Berlin; New York: Springer, c2000. ISBN: 3540675671

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

34

Books 159

http://www.amazon.com/exec/obidos/ASIN/3540675671/icongroupin terna ·

Campath-1H: emerging frontline therapy in chronic lymphocytic leukemia. Author: Kanti R. Rai and Janet Stephenson; Year: 2001; New York: Parthenon Pub. Group, c2001. ISBN: 1842140604 http://www.amazon.com/exec/obidos/ASIN/1842140604/icongroupin terna

·

Chronic leukemia: approach to diagnosis. Author: Harold R. Schumacher, James D. Cotelingam; Year: 1993; New York: Igaku-Shoin, c1993. ISBN: 0896402207 http://www.amazon.com/exec/obidos/ASIN/0896402207/icongroupin terna

·

Chronic lymphocytic leukemia: recent progress and future direction: proceedings of a Hyland Laboratories-UCLA symposium held in Napa, California, December 2-5, 1986. Author: editors, Robert Peter Gale, Kanti R. Rai; Year: 1987; New York: Liss, c1987. ISBN: 084512658X http://www.amazon.com/exec/obidos/ASIN/084512658X/icongroupi nterna

·

Chronic lymphocytic leukemia. Author: edited by Aaron Polliack and Daniel Catovsky; Year: 1988; Chur; New York: Harwood Academic Publishers, c1988. ISBN: 3718648024 http://www.amazon.com/exec/obidos/ASIN/3718648024/icongroupin terna

·

Chronic lymphoid leukemias. Author: edited by Bruce D. Cheson; Year: 2001; New York: Marcel Dekker, c2001. ISBN: 0824705432 http://www.amazon.com/exec/obidos/ASIN/0824705432/icongroupin terna

·

Chronic myelocytic leukemia and interferon: pathophysiological, clinical, and therapeutical aspects. Author: D. Huhn, K.P. Hellriegel, N. Niederle (eds.); Year: 1988; Berlin; New York: Springer Verlag, c1988. ISBN: 0387190678 http://www.amazon.com/exec/obidos/ASIN/0387190678/icongroupin terna

·

Chronic myelogenous leukemia: molecular approaches to research and therapy. Author: edited by Albert B. Deisseroth, Ralph B. Arlinghaus; Year: 1991; New York: Dekker, c1991. ISBN: 0824783522 http://www.amazon.com/exec/obidos/ASIN/0824783522/icongroupin terna

·

Chronic myeloid leukaemia: biology and treatment. Author: edited by Angelo M. Carella ... [et al.]; Year: 2001; London: Martin Dunitz; Florence, KY: Distributed in the USA by Taylor ; Francis, c2001. ISBN: 185317890X


http://www.amazon.com/exec/obidos/ASIN/185317890X/icongroupi nterna ·

Chronic myeloid leukemia and blastic crisis. Author: guest editor, Michele Baccarani; Year: 1975; Copenhagen: Munksgaard, 1975. ISBN: 8716023870

·

Clinical applications of flow cytometry: immunophenotyping of leukemic cells; approved guideline. Author: M. Borowitz ... [et al.]; Year: 1998; Wayne, PA: NCCLS, 1998. ISBN: 1562383515

·

Clinical, hematological and pathological features of the terminal phase of chronic myelogenous leukemia. Author: Morrow, George William, 1925-; Year: 1957; [Minneapolis] 1957.

·

Current management of childhood leukemia. Author: Alvin M. Mauer, consulting reviewer; Year: 1991; Bethesda, MD: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, International Cancer Research Data Bank; Washington, D.C.: For sale by the Supt. of Docs., U.S. G.P.O., [1991]

·

Cytogenetic evolution in chronic myelogenous leukaemia: relation of chromosomes to progression and treatment of the disease. Author: Pedersen, Bent, 1933-; Year: 1969; Copenhagen: Munksgaard, 1969.

·

Effect of urethane and several urethane derivatives on transplanted myelogenous leukemia in the mouse. Author: Winchester, William Wellington, 1913-; Year: 1952; [Minneapolis] 1952.

·

Fludarabine in the treatment of chronic lymphocytic leukaemia. Author: L. Best; Year: 1995; Bristol, England: U.K. National Health Service, South and West Regional Health Authority, 1995.

·

Functional characterization of blood lymphocytes in chronic lymphocytic leukemia. Author: Karl-Henrik Robèrt; Year: 1979; Stockholm: [s.n.], 1979.

·

Hairy cell and chronic lymphocytic leukemia: thirty years of progress. Author: edited by Andrew T. Huang; Year: 1987; New York: Elsevier, c1987. ISBN: 0444012338 http://www.amazon.com/exec/obidos/ASIN/0444012338/icongroupin terna

·

Medical management of chronic myelogenous leukemia. Author: edited by Moshe Talpaz, Hagop M. Kantarjian; Year: 1998; New York,: Dekker, c1999. ISBN: 0824799011 http://www.amazon.com/exec/obidos/ASIN/0824799011/icongroupin terna

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·

Monocytes, monocytosis, and monocytic leukemia, by Lawrence Kass and Bertram Schnitzer. Author: Kass, Lawrence, 1938-; Year: 1973; Springfield, Ill., Thomas [c1973] ISBN: 0398028834 http://www.amazon.com/exec/obidos/ASIN/0398028834/icongroupin terna

·

Monocytic leukemia. Author: Ingram, David Wallace, 1926-; Year: 1961; [Minneapolis] 1961.

·

Myelodysplastic syndromes & secondary acute myelogenous leukemia: directions for the new millennium. Author: edited by Azra Raza, Suneel D. Mundle; Year: 2001; Boston: Kluwer Academic Publishers, c2001. ISBN: 0792373960 http://www.amazon.com/exec/obidos/ASIN/0792373960/icongroupin terna

·

Proceedings of the USPHS Workshop on Laboratory and Epidemiologic Approaches to Determining the Role of Environmental Exposure as Risk Factors for B-Cell Chronic Lymphocytic Leukemia and Other B-Cell Lymphoproliferative Disorders. Author: edited by Gerald E. Mar; Year: 1997; Atlanta, Ga.: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention: Food and Drug Administration: Agency for Toxic Substances and Disease Registry: National Institutes of Health, [1997]

·

Studies on tumor immunity and lymphocyte kinetics in vitro in acute and chronic lymphatic leukemia. Author: Maria Johanna Helena Schweitzer; Year: 1973; [Amsterdam?: s.n., 1973]

·

Veterans and agent orange. Herbicide. Author: dioxin exposure and acute myelogenous leukemia in the children of Vietnam veterans / Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides, Division of Health Promotion and Disease Preven; Year: 2002; Washington, D.C.: National Academy Press, c2002. ISBN: 0309083389

Chapters on Chronic Lymphocytic Leukemia Frequently, chronic lymphocytic leukemia will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with chronic lymphocytic leukemia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and chronic lymphocytic leukemia using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search


by.” Select the dates and language you prefer, and the format option “Book Chapter.” By making these selections and typing in “chronic lymphocytic leukemia” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on chronic lymphocytic leukemia: ·

Cancer Incidence, Mortality, and Patient Survival in the United States Source: in Cancer Epidemiology and Prevention. Second Edition. Schottenfeld, D.; Fraumeni, J.F.; eds. New York, NY, Oxford University Press, pp. 168-191, 1996. Contact: Oxford University Press, Inc., 198 Madison Avenue, New York, NY 10016. Summary: Cancer Incidence, Mortality, and Patient Survival in the United States, a book chapter in Cancer Epidemiology and Prevention, Second Edition, presents data on the incidence of cancer, cancer mortality, and patient survival, using Surveillance, Epidemiology and End Results (SEER) data and mortality information provided by the National Center for Health Statistics. SEER collects information on the demographic characteristics of the patient, anatomic site of the malignancy, histologic cell type, extent (state) of the disease at the time of diagnosis, treatment, and followup, including survival status and cause of death. Incidence and mortality data are based on 479,729 newly diagnosed malignancies, 213,315 cancer deaths among residents of the SEER areas, and 2,432,671 cancer deaths in the United States between 1987-1991. During 1994, approximately 1,208,000 malignancies were diagnosed and 538,000 persons died as a result of cancer. Between 19731991, the overall cancer mortality rates increased only slightly (between 7 percent and 8 percent), while incidence rates increased 31 percent and 14 percent among males and females, respectively. Overall cancer incidence (1987-1991) was highest among black males, followed by white males, white females, and black females. Malignancies of the digestive system currently account for nearly 20 percent of all cancer in the United States. Of these, 64 percent arise in the colon and rectum, 12 percent in the pancreas, and 10 percent in the stomach. Incidence of melanoma of the skin increased 94 percent from 1973-1991, which was more rapid than for any other major primary site except for female lung cancer and male prostate cancer. There were approximately 183,000 diagnoses of invasive breast cancer in 1994. For females diagnosed with breast cancer between 1983-1990, survival was poorer for blacks than for whites, with 5-year relative rates of 66 percent and 82 percent, respectively. Cancers of the corpus uteri and uterus not otherwise specified accounted for over 40 percent of all malignancies of the female reproductive system. Ovarian

Books 163

cancer accounted for 32 percent of such malignancies and cervical cancer, 20 percent. Survival rates have improved in the last several decades, most notably for acute lymphocytic leukemia among children. However, incidence rates for many other childhood cancers have continued to rise.

General Home References In addition to references for chronic lymphocytic leukemia, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Cancer: 50 Essential Things to Do by Greg Anderson, O. Carl Simonton; Paperback - 184 pages; Revised & Updated edition (August 1999), Plume; ISBN: 0452280745; http://www.amazon.com/exec/obidos/ASIN/0452280745/icongroupinterna · Cancer Encyclopedia -- Collections of Anti-Cancer & Anti-Carcinogenic Agents, Chemicals, Drugs and Substances by John C. Bartone; Paperback (January 2002), ABBE Publishers Association of Washington, DC; ISBN: 0788326791; http://www.amazon.com/exec/obidos/ASIN/0788326791/icongroupinterna · Cancer Sourcebook: Basic Consumer Health Information About Major Forms and Stages of Cancer by Edward J. Prucha (Editor); Library Binding - 1100 pages, 3rd edition (August 1, 2000), Omnigraphics, Inc.; ISBN: 0780802276; http://www.amazon.com/exec/obidos/ASIN/0780802276/icongroupinterna · Cancer Supportive Care: A Comprehensive Guide for Patients and Their Families by Ernest H. Rosenbaum, M.D., Isadora Rosenbaum, M.A.; Paperback - 472 pages (November 5, 1998), Somerville House Books Limited; ISBN: 1894042115; http://www.amazon.com/exec/obidos/ASIN/1894042115/icongroupinterna · Cancer Symptom Management: Patient Self-Care Guides (Book with CD-ROM for Windows & Macintosh) by Connie Henke Yarbro (Editor), et al; CD-ROM - 264 pages, 2nd Book & CD-Rom edition (January 15, 2000), Jones & Bartlett Publishing; ISBN: 0763711675; http://www.amazon.com/exec/obidos/ASIN/0763711675/icongroupint erna · Diagnosis Cancer: Your Guide Through the First Few Months by Wendy Schlessel Harpham, Ann Bliss Pilcher (Illustrator); Paperback: 230 pages;


Revised & Updated edition (November 1997), .W. Norton & Company; ISBN: 0393316912; http://www.amazon.com/exec/obidos/ASIN/0393316912/icongroupinterna · The Human Side of Cancer: Living with Hope, Coping with Uncertainty by Jimmie C. Holland, M.D., Sheldon Lewis; Paperback - 368 pages (October 2, 2001), Quill; ISBN: 006093042X; http://www.amazon.com/exec/obidos/ASIN/006093042X/icongroupinterna

Vocabulary Builder Carcinogenic: Producing carcinoma. [EU] Corpus: The body of the uterus. [NIH] Herbicide: A chemical that kills plants. [NIH] Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry. [NIH] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Kinetic: Pertaining to or producing motion. [EU] Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Pancreas: A glandular organ located in the abdomen. It makes pancreatic juices, which contain enzymes that aid in digestion, and it produces several hormones, including insulin. The pancreas is surrounded by the stomach, intestines, and other organs. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Stomach: An organ that is part of the digestive system. It helps in the digestion of food by mixing it with digestive juices and churning it into a thin liquid. [NIH]

Books 165

Urethane: Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH]

Multimedia 167

CHAPTER 7. MULTIMEDIA ON CHRONIC LYMPHOCYTIC LEUKEMIA Overview Information on chronic lymphocytic leukemia can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on chronic lymphocytic leukemia. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine. If you see an interesting item, visit your local medical library to check on the availability of the title.

Bibliography: Multimedia on Chronic Lymphocytic Leukemia The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in chronic lymphocytic leukemia (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on chronic lymphocytic leukemia. For more information, follow the hyperlink indicated:


·

Acute and chronic leukemias. Source: [produced and published by Gower Medical Publishing]; Year: 1991; Format: Slide; New York, NY: Gower Medical Pub., c1991.

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Acute and chronic leukemias. Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1982; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1982.

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Acute leukemia. Source: [American Society of Hematology]; Year: 1974; Format: Slide; [Seattle: The Society: for sale by University of Washington Health Sciences Center for Educational Resources, 1974]

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Basic hematology. Source: Trainex Corporation; Year: 1972; Format: Filmstrip; [Garden Grove, Calif.]: Trainex, c1972.

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Bone marrow aspiration biopsy. Source: Cleveland Clinic Foundation; Year: 1976; Format: Videorecording; Cleveland: The Foundation, 1976.

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Care of the patient with leukemia. Source: Trainex Corporation; Year: 1970; Format: Filmstrip; Garden Grove, Calif.: Trainex, c1970.

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Chronic lymphatic leukemia . Year: 1984; Format: Slide; Columbus, Ohio: Center for Continuing Medical Education, the Ohio State University College of Medicine, 1984.

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Chronic lymphatic leukemia. Source: [Henry E.] Wilson; produced by Ohio State University, Medical Audiovisual and Television Center; Year: 1971; Format: Videorecording; [Columbus, Ohio]: The Center, c1971.

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Chronic lymphocytic leukemia. Source: author, Charles Koller; faculty consultant, Roland Hiss; Biomedical Media Production Unit, the University of Michigan Medical Center, Office of Educational Resources & Research; Year: 1981; Format: Videorecording; Ann Arbor, Mich.: University of Michigan, c1981.

·

Chronic myelogenous leukemia. Source: [presented by] the University of Texas Medical School at Houston; produced by UT/TV, Houston, the University of Texas Health Science Center at Houston; Year: 1990; Format: Videorecording; [Houston, Tex.: UT-TV], c1990.

·

Current myelogenous leukemia. Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital [and] Marshfield Medical Research Foundation; Year: 1990; Format: Videorecording; Marshfield, WI: Marshfield Video Network, [1990]

·

Diseases of the blood : issues and answers. Source: [a presentation of Films for the Humanities & Sciences; produced by Information Television Network in association with the Multiple Myeloma Research Foundation and the Leukemia Society of Amer; Year: 2000; Format: Videorecording; Princeton, N.J.: Films for the Humanities ; Sciences, c2000.

Multimedia 169

·

Hematuria : don't stop the workup too soon. Source: Vincent J. 0'Conor, Jr. Acute myelogenous leukemia: the diagnosis; Acute myelogenous leukemia: the treatment / Monroe Dowling; Year: 1975; Format: Videorecording; New York: Network for Continuing Medical Education, 1975.

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Hemophilia. Source: [Stanley P.] Balcerzak; produced by Ohio State University, Medical Audiovisual and Television Center; Year: 1971; Format: Videorecording; [Columbus, Ohio]: The Center, c1971.

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Hodgkins disease. Source: [Stanley P.] Balcerzak; produced by Ohio State University, Medical Audiovisual and Television Center; Year: 1971; Format: Videorecording; [Columbus, Ohio]: The Center, c1971.

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Interabdominal lymphosarcoma. Source: [Albert F.] LoBuglio; produced by Ohio State University, Medical Audiovisual and Television Center; Year: 1971; Format: Videorecording; [Columbus, Ohio]: The Center, c1971.

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Iron deficiency anemia. Source: [Albert F.] LoBuglio; produced by Ohio State University, Medical Audiovisual and Television Center; Year: 1971; Format: Videorecording; [Columbus, Ohio]: The Center, c1971.

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Leukemia : ASCO fall conference. Year: 1990; Format: Sound recording; Chicago, IL: Teach'em, [1990]

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Leukemia: a bird's eye view : food for thought. Source: Health Sciences McMaster University; produced by Audio Visual Services, McMaster University; Year: 1972; Format: Slide; [Hamilton, Ont.]: Health Sciences McMaster Univ., 1972.

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Leukemia in children. Source: Medical Electronic Educational Services; produced by School of Nursing University of Missouri-Columbia; Year: 1973; Format: Filmstrip; Columbia: The University, c1973.

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Leukemias. Source: James W. Linman; Year: 1971; Format: Slide; New York: Medcom, c1971.

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Lymphocytic leukemia: acute and chronic. Source: Virginia Minnich, J. Mark Michael; Year: 1982; Format: Slide; Chicago: American Society of Clinical Pathologists, c1982.

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Morphology of white blood cells. Source: Cleveland Clinic Educational Foundation; Year: 1975; Format: Videorecording; Cleveland, Ohio: The Foundation; [for sale by Cleveland Clinic Educational Foundation, Audiovisual Dept.], 1975.

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Multiple myeloma. Source: [Albert F.] LoBuglio; produced by Ohio State University, Medical Audiovisual and Television Center; Year: 1971; Format: Videorecording; [Columbus, Ohio]: The Center, c1971.


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Myelocytic leukemia: chronic and acute. Source: Virginia Minnich; Year: 1982; Format: Slide; Chicago: American Society of Clinical Pathologists, c1982.

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New strategies in chronic granulocytic leukemia. Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1982; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1982.

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Normal & abnormal marrow: cellular elements. Source: American Society of Hematology; Year: 1973; Format: Slide; Seattle: The Society: [for loan or sale by Univ. of Washington Health Sciences Center for Educational Resources, 1973].

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Oral manifestations of blood diseases. Source: produced by American Dental Association, Council on Dental Therapeutics; Year: 1968; Format: Slide; Chicago, Ill.: The Association, 1968.

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Teaching a child about leukemia. Source: Madeline Petrillo; Year: 1975; Format: Filmstrip; Scarsdale, N. Y.: Steve Campus Productions: [for sale by Campus Film Distributors], c1975.

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X-ray findings related to hemoglobinopathies. Source: M. I. Goldstein; produced by Ohio State University, Medical Audio-visual and Television Center; Year: 1972; Format: Videorecording; [Columbus, Ohio]: The Center, c1972.

Vocabulary Builder Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Lymphosarcoma: An obsolete term for a malignant tumor of lymphatic tissue. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH]

Periodicals and News 171

CHAPTER 8. PERIODICALS AND NEWS ON CHRONIC LYMPHOCYTIC LEUKEMIA Overview Keeping up on the news relating to chronic lymphocytic leukemia can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on chronic lymphocytic leukemia. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover chronic lymphocytic leukemia beyond and including those which are published by patient associations mentioned earlier. We will first focus on news services, and then on periodicals. News services, press releases, and newsletters generally use more accessible language, so if you do chose to subscribe to one of the more technical periodicals, make sure that it uses language you can easily follow.

News Services & Press Releases Well before articles show up in newsletters or the popular press, they may appear in the form of a press release or a public relations announcement. One of the simplest ways of tracking press releases on chronic lymphocytic leukemia is to search the news wires. News wires are used by professional journalists, and have existed since the invention of the telegraph. Today, there are several major “wires” that are used by companies, universities, and other organizations to announce new medical breakthroughs. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing.


PR Newswire Perhaps the broadest of the wires is PR Newswire Association, Inc. To access this archive, simply go to http://www.prnewswire.com. Below the search box, select the option “The last 30 days.” In the search box, type “chronic lymphocytic leukemia” or synonyms. The search results are shown by order of relevance. When reading these press releases, do not forget that the sponsor of the release may be a company or organization that is trying to sell a particular product or therapy. Their views, therefore, may be biased. The following is typical of press releases that can be found on PR Newswire: ·

Encouraging Results Reported on TRISENOX(R) in Myelodysplasia and Chronic Myeloid Leukemia at International Conference Summary: Shanghai, China, Nov. 8 /PRNewswire-FirstCall/ -- In a satellite symposium in conjunction with the Chinese Society of Hematology 2002 Conference, researchers presented data from clinical trials indicating that arsenic trioxide may be effective in inducing high rates of remission in hematologic malignancies like myelodysplasia (MDS) and chronic myeloid leukemia (CML). TRISENOX(R) (arsenic trioxide) is marketed by Cell Therapeutics, Inc. (CTI) (Nasdaq: CTIC). Ma Jun, M.D., of Harbin Institute of Hematology reported on the clinical efficacy of arsenic trioxide in treating MDS. In 21 patients with MDSrefractory anemia (MDS-RA), six patients (29 percent) achieved a complete remission (CR) and eight patients (38 percent) achieved a partial remission (PR) for an overall objective response rate of 67 percent. Complete remission was maintained for three years. In 18 patients with MDS-refractory anemia with excess blasts (MDS-RAEB), three patients achieved stable disease (SD) or better (one PR and two SD). Dr. Ma also provided data on the clinical efficacy of arsenic trioxide among patients with CML. In a study of 29 patients with newly diagnosed CML, 19 patients (66 percent) achieved a CR with four patients achieving a PR for an overall response rate of 79 percent. Safety analyses for these clinical studies were not provided. Mechanistic insights into the multiple mechanisms of action by which arsenic trioxide may lead to apoptosis of cancer cells were also elucidated in preclinical sessions. These concluded that arsenic trioxide could prove effective alone or in combination with radiation or standard chemotherapy against a wide variety of tumors.


Reuters The Reuters’ Medical News database can be very useful in exploring news archives relating to chronic lymphocytic leukemia. While some of the listed articles are free to view, others can be purchased for a nominal fee. To access this archive, go to http://www.reutershealth.com/frame2/arch.html and search by “chronic lymphocytic leukemia” (or synonyms). The following was recently listed in this archive for chronic lymphocytic leukemia: ·

Interferon-alpha and cytarabine useful in pediatric chronic myeloid leukemia Source: Reuters Industry Breifing Date: February 14, 2002 http://www.reuters.gov/archive/2002/02/14/business/links/20020214 clin004.html

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Early results promising for new drug for chronic myeloid leukemia Source: Reuters Medical News Date: December 04, 2000 http://www.reuters.gov/archive/2000/12/04/professional/links/20001 204drgd006.html

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Unrelated donor bone marrow transplantation cost-effective for chronic myelogenous leukemia Source: Reuters Medical News Date: January 01, 1999 http://www.reuters.gov/archive/1999/01/01/professional/links/19990 101econ001.html

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Interferon Plus Cytarabine Effective In Chronic Myelogenous Leukemia Patients Source: Reuters Medical News Date: July 24, 1997 http://www.reuters.gov/archive/1997/07/24/professional/links/19970 724clin008.html

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Interferon-Alpha: Cost-Effective Treatment For Chronic Myelogenous Leukemia Source: Reuters Medical News Date: October 01, 1996 http://www.reuters.gov/archive/1996/10/01/professional/links/19961 001econ001.html


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Interferon Therapy Effective In Older Patients With Chronic Myelogenous Leukemia Source: Reuters Medical News Date: April 12, 1996 http://www.reuters.gov/archive/1996/04/12/professional/links/19960 412clin006.html

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Roferon-A Cleared For Treatment Of Chronic Myelogenous Leukemia Source: Reuters Medical News Date: November 20, 1995 http://www.reuters.gov/archive/1995/11/20/professional/links/19951 120rglt001.html

The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within their search engine.

Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com. You can scan the news by industry category or company name.

Internet Wire Internet Wire is more focused on technology than the other wires. To access this site, go to http://www.internetwire.com and use the “Search Archive” option. Type in “chronic lymphocytic leukemia” (or synonyms). As this service is oriented to technology, you may wish to search for press releases covering diagnostic procedures or tests that you may have read about.


Search Engines Free-to-view news can also be found in the news section of your favorite search engines (see the health news page at Yahoo: http://dir.yahoo.com/Health/News_and_Media/, or use this Web site’s general news search page http://news.yahoo.com/. Type in “chronic lymphocytic leukemia” (or synonyms). If you know the name of a company that is relevant to chronic lymphocytic leukemia, you can go to any stock trading Web site (such as www.etrade.com) and search for the company name there. News items across various news sources are reported on indicated hyperlinks.

BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “chronic lymphocytic leukemia” (or synonyms).

Newsletters on Chronic Lymphocytic Leukemia Given their focus on current and relevant developments, newsletters are often more useful to patients than academic articles. You can find newsletters using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Your investigation must limit the search to “Newsletter” and “chronic lymphocytic leukemia.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” By making these selections and typing in “chronic lymphocytic leukemia” or synonyms into the “For these words:” box, you will only receive results on newsletters.

Academic Periodicals Covering Chronic Lymphocytic Leukemia Academic periodicals can be a highly technical yet valuable source of information on chronic lymphocytic leukemia. We have compiled the following list of periodicals known to publish articles relating to chronic lymphocytic leukemia and which are currently indexed within the National Library of Medicine’s PubMed database (follow hyperlinks to view more


information, summaries, etc., for each). In addition to these sources, to keep current on articles written on chronic lymphocytic leukemia published by any of the periodicals listed below, you can simply follow the hyperlink indicated or go to the following Web site: www.ncbi.nlm.nih.gov/pubmed. Type the periodical’s name into the search box to find the latest studies published. If you want complete details about the historical contents of a periodical, you can also visit the Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/ you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.” The following is a sample of periodicals which publish articles on chronic lymphocytic leukemia: ·

Acta Haematologica. (Acta Haematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ac ta+Haematologica&dispmax=20&dispstart=0

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American Journal of Hematology. (Am J Hematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=A merican+Journal+of+Hematology&dispmax=20&dispstart=0

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Annals of Hematology. (Ann Hematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=An nals+of+Hematology&dispmax=20&dispstart=0

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Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. (Ann Oncol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=An nals+of+Oncology+:+Official+Journal+of+the+European+Society+for+M edical+Oncology+/+Esmo&dispmax=20&dispstart=0

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Annual Review of Medicine. (Annu Rev Med) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=An nual+Review+of+Medicine&dispmax=20&dispstart=0


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Bone Marrow Transplantation. (Bone Marrow Transplant) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Bo ne+Marrow+Transplantation&dispmax=20&dispstart=0

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Cancer Gene Therapy. (Cancer Gene Ther) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ca ncer+Gene+Therapy&dispmax=20&dispstart=0

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Cancer Genetics and Cytogenetics. (Cancer Genet Cytogenet) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ca ncer+Genetics+and+Cytogenetics&dispmax=20&dispstart=0

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Cancer Practice. (Cancer Pract) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ca ncer+Practice&dispmax=20&dispstart=0

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Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. (Clin Cancer Res) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Cli nical+Cancer+Research+:+an+Official+Journal+of+the+American+Associ ation+for+Cancer+Research&dispmax=20&dispstart=0

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Clinical Rheumatology. (Clin Rheumatol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Cli nical+Rheumatology&dispmax=20&dispstart=0

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Diagnostic Cytopathology. (Diagn Cytopathol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Di agnostic+Cytopathology&dispmax=20&dispstart=0

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Environmental Health Perspectives. (Environ Health Perspect) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=En vironmental+Health+Perspectives&dispmax=20&dispstart=0

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European Journal of Haematology. (Eur J Haematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Eu ropean+Journal+of+Haematology&dispmax=20&dispstart=0


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Experimental Hematology. (Exp Hematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ex perimental+Hematology&dispmax=20&dispstart=0

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Genes, Chromosomes & Cancer. (Genes Chromosomes Cancer) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ge nes,+Chromosomes+&+Cancer&dispmax=20&dispstart=0

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Haematologia. (Haematologia (Budap)) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ha ematologia&dispmax=20&dispstart=0

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Human Pathology. (Hum Pathol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=H uman+Pathology&dispmax=20&dispstart=0

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International Journal of Hematology. (Int J Hematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Int ernational+Journal+of+Hematology&dispmax=20&dispstart=0

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Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. (J Pediatr Hematol Oncol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Pediatric+Hematology/Oncology+:+Official+Journal+of+the+ American+Society+of+Pediatric+Hematology/Oncology&dispmax=20& dispstart=0

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Leukemia & Lymphoma. (Leuk Lymphoma) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Le ukemia+&+Lymphoma&dispmax=20&dispstart=0

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Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. (Med Sci Monit) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=M edical+Science+Monitor+:+International+Medical+Journal+of+Experime ntal+and+Clinical+Research&dispmax=20&dispstart=0


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Neurology India. (Neurol India) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ne urology+India&dispmax=20&dispstart=0

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Proceedings of the National Academy of Sciences of the United States of America. (Proc Natl Acad Sci U S A) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Pr oceedings+of+the+National+Academy+of+Sciences+of+the+United+Stat es+of+America&dispmax=20&dispstart=0

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The Journal of Biological Chemistry. (J Biol Chem) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Th e+Journal+of+Biological+Chemistry&dispmax=20&dispstart=0

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The New England Journal of Medicine. (N Engl J Med) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Th e+New+England+Journal+of+Medicine&dispmax=20&dispstart=0

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The Oncologist. (Oncologist) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Th e+Oncologist&dispmax=20&dispstart=0

Vocabulary Builder Arthralgia: Pain in a joint. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Coagulation: 1. the process of clot formation. 2. in colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. in surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Dyspnea: Difficult, painful breathing or shortness of breath. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Hyperglycemia: Abnormally high blood sugar. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Intravascular: Within a vessel or vessels. [EU]


Myelodysplasia: Abnormal bone marrow cells that may lead to myelogenous leukemia. [NIH]

Physician Guidelines and Databases 181

CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help patients with their conditions. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.

NIH Guidelines For the more common diseases, The National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Cancer Institute (NCI); guidelines available at http://cancernet.nci.nih.gov/pdq/pdq_treatment.shtml


In this chapter, we begin by reproducing one such guideline for chronic lymphocytic leukemia:

What Is Chronic Lymphocytic Leukemia?35 Chronic lymphocytic leukemia (CLL) is a disorder of morphologically mature but immunologically less mature lymphocytes and is manifested by progressive accumulation of these cells in the blood, bone marrow, and lymphatic tissues. Lymphocyte counts in the blood are usually equal to or higher than 10,000 per cubic millimeter.36 Treatment with conventional doses of chemotherapy is not curative; selected patients treated with allogeneic stem cell transplantation have achieved prolonged disease-free survival.37 The overall 5-year survival is approximately 60%, but depends on stage of disease. Antileukemic therapy is frequently unnecessary in uncomplicated early disease.38 CLL occurs primarily in middle-aged and elderly individuals, with increasing frequency in successive decades of life.39 The clinical course of this disease progresses from an indolent lymphocytosis without other evident disease to one of generalized lymphatic enlargement with concomitant The following guidelines appeared on the NCI Web site on Aug. 26, 2002. The text was last modified in July 2002. The text has been adapted for this sourcebook. Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.) 36 Chronic lymphocytic leukemia: recommendations for diagnosis, staging, and response criteria. International Workshop on Chronic Lymphocytic Leukemia. Annals of Internal Medicine 110(3): 236-238, 1989. 37 van Besien K, Keralavarma B, Devine S, et al.: Allogeneic and autologous transplantation for chronic lymphocytic leukemia. Leukemia 15(9): 1317-1325, 2001. Esteve J, Villamor N, Colomer D, et al.: Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status. Leukemia 15(3): 445-451, 2001. Toze CL, Shepherd JD, Connors JM, et al.: Allogeneic bone marrow transplantation for lowgrade lymphoma and chronic lymphocytic leukemia. Bone Marrow Transplantation 25(6): 605-612, 2000. Pavletic ZS, Arrowsmith ER, Bierman PJ, et al.: Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia. Bone Marrow Transplantation 25(7): 717-722, 2000. 38 Rozman C, Montserrat E: Chronic lymphocytic leukemia. New England Journal of Medicine 333(16): 1052-1057, 1995. 39 Catovsky D, Fooks J, Richards S: Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival: a report from the MRC CLL 1 trial. British Journal of Haematology 72(2): 141-149, 1989. 35


pancytopenia. Complications of pancytopenia, including hemorrhage and infection, represent a major cause of death in these patients.40 Immunological aberrations, including Coombs-positive hemolytic anemia, immune thrombocytopenia, and depressed immunoglobulin levels may all complicate the management of CLL.41 Prognostic factors that may help predict clinical outcome include cytogenetic subgroup42 and CD38 expression.43 Confusion with other diseases may be avoided by determination of cell surface markers. CLL lymphocytes coexpress the B-cell antigens CD19 and CD20 along with the T-cell antigen CD5.44 This coexpression only occurs in one other disease entity, mantle cell lymphoma. CLL B cells express relatively low levels of surface-membrane immunoglobulin (compared with normal peripheral blood B cells) and a single light chain (kappa or lambda).45 CLL is diagnosed by an absolute increase in lymphocytosis and/or bone marrow infiltration coupled with the characteristic features of morphology and immunophenotype. The differential diagnosis must exclude hairy cell leukemia (refer to the PDQ summary on Hairy Cell Leukemia Treatment for more information), and Waldenstrom’s macroglobulinemia (refer to the PDQ summary on Multiple Myeloma and Other Plasma Cell Neoplasms Treatment for more information). Waldenstrom’s macroglobulinemia has a natural history and therapeutic options similar to CLL, with the exception of hyperviscosity syndrome associated with macroglobulinemia as a result of elevated immunoglobulin M. Prolymphocytic leukemia (PLL) is a rare entity characterized by excessive prolymphocytes in the blood with a typical phenotype that is positive for CD19, CD20, and surface-membrane immunoglobulin and negative for CD5. These patients demonstrate Anaissie EJ, Kontoyiannis DP, O’Brien S, et al.: Infections in patients with chronic lymphocytic leukemia treated with fludarabine. Annals of Internal Medicine 129(7): 559566, 1998. 41 Mauro FR, Foa R, Cerretti R, et al.: Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features. Blood 95(9): 2786-2792, 2000. 42 Dohner H, Stilgenbauer S, Benner A, et al.: Genomic aberrations and survival in chronic lymphocytic leukemia. New England Journal of Medicine 343(26): 1910-1916, 2000. 43 Del Poeta G, Maurillo L, Venditti A, et al.: Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood 98(9): 2633-2639, 2001. Ibrahim S, Keating M, Do KA, et al.: CD38 expression as an important prognostic factor in Bcell chronic lymphocytic leukemia. Blood 98(1): 181-186, 2001. 44 DiGiuseppe JA, Borowitz MJ: Clinical utility of flow cytometry in the chronic lymphoid leukemias. Seminars in Oncology 25(1): 6-10, 1998. 45 Rozman C, Montserrat E: Chronic lymphocytic leukemia. New England Journal of Medicine 333(16): 1052-1057, 1995. 40


splenomegaly and poor response to low-dose or high-dose chemotherapy.46 Cladribine (2-chlorodeoxyadenosine) appears to be an active agent (60% complete remission rate) for patients with de novo B-cell prolymphocytic leukemia.47 [Level of evidence: 3iiiDiii] Patients with CLL who show prolymphocytoid transformation maintain the classic CLL phenotype and have a worse prognosis than PLL patients. Large granular lymphocytic leukemia is characterized by lymphocytosis with a natural killer cell immunophenotype (CD2, CD16, and CD56) or a T-cell immunophenotype (CD2, CD3, and CD8).48 These patients often have neutropenia and a history of rheumatoid arthritis. The natural history is indolent, often marked by anemia and splenomegaly. This condition appears to fit into the clinical spectrum of Felty’s syndrome.49 Therapy includes steroids, low doses of oral cyclophosphamide or methotrexate, and treatment of the bacterial infections acquired during severe neutropenia.50

Stage Information Staging is useful in this disease to predict prognosis and also to stratify patients to achieve comparability of interpreting specific treatment results. Anemia and thrombocytopenia are the major adverse prognostic variables. Chronic lymphocytic leukemia (CLL) has no standard staging system. The Rai staging system and the Binet classification are presented below.51 An Rozman C, Montserrat E: Chronic lymphocytic leukemia. New England Journal of Medicine 333(16): 1052-1057, 1995. Melo JV, Catovsky D, Galton DA: The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia: I. Clinical and laboratory features of 300 patients and characterization of an intermediate group. British Journal of Haematology 63: 377-387, 1986. 47 Saven A, Lee T, Schlutz M, et al.: Major activity of cladribine in patients with de novo Bcell prolymphocytic leukemia. Journal of Clinical Oncology 15(1): 37-43, 1997. 48 Loughran TP: Clonal diseases of large granular lymphocytes. Blood 82(1): 1-14, 1993. Semenzato G, Zambello R, Starkebaum G, et al.: The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood 89(1): 256-260, 1997. 49 Bowman SJ, Sivakumaran M, Snowden N, et al.: The large granular lymphocyte syndrome with rheumatoid arthritis: immunogenetic evidence for a broader definition of Felty’s syndrome. Arthritis and Rheumatism 37(9): 1326-1330, 1994. 50 Loughran TP: Clonal diseases of large granular lymphocytes. Blood 82(1): 1-14, 1993. Loughran TP, Kidd PG, Starkebaum G: Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. Blood 84(7): 2164-2170, 1994. Dhodapkar MV, Li CY, Lust JA, et al.: Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? Blood 84(5): 16201627, 1994. 51 Rai KR, Sawitsky A, Cronkite EP, et al.: Clinical staging of chronic lymphocytic leukemia. Blood 46(2): 219-234, 1975. 46


NCI-sponsored working group has formulated standardized guidelines for eligibility, response, and toxic effects criteria to be used in future clinical trials in CLL.52

Rai Staging System Stage 0 Stage 0 chronic lymphocytic leukemia: absolute lymphocytosis (>15,000 per cubic millimeter) without adenopathy, hepatosplenomegaly, anemia, or thrombocytopenia. Stage I Stage I chronic lymphocytic leukemia: absolute lymphocytosis with lymphadenopathy without hepatosplenomegaly, anemia, or thrombocytopenia.

Stage II Stage II chronic lymphocytic leukemia: absolute lymphocytosis with either hepatomegaly or splenomegaly, with or without lymphadenopathy. Stage III Stage III chronic lymphocytic leukemia: absolute lymphocytosis and anemia (hemoglobin

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