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主页 The Gale Encyclopedia of Cancer (Two Volume Set)
The Gale Encyclopedia of Cancer (Two Volume Set)Ellen Thackery
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The GALE ENCYCLOPEDIA of Cancer The GALE ENCYCLOPEDIA of Cancer A GUIDE TO CANCER AND ITS TREATMENTS VO L U M E 1 A-K E L L E N T H A C K E R Y, E D I T O R The GALE ENCYCLOPEDIA of CANCER STAFF Ellen Thackery, Project Editor Christine B. Jeryan, Managing Editor Donna Olendorf, Senior Editor Stacey Blachford, Associate Editor Kate Kretschmann, Editorial Intern Mark Springer, Technical Specialist Andrea Lopeman, Programmer/Analyst Barbara Yarrow, Manager, Imaging and Multimedia Content Robyn V. Young, Project Manager, Imaging and Multimedia Content Randy Bassett, Imaging Supervisor Dan Newell, Imaging Specialist Pamela A. Reed, Coordinator, Imaging and Multimedia Content Maria Franklin, Permissions Manager Margaret A. Chamberlain, Permissions Specialist Kenn Zorn, Product Manager Michelle DiMercurio, Senior Art Director, Page Design Pamela A. E. Galbreath, Senior Art Director, Cover Design Mary Beth Trimper, Manager, Composition and Electronic Prepress Evi Seoud, Assistant Manager, Composition Purchasing and Electronic Prepress Dorothy Maki, Manufacturing Manager Indexing provided by Synapse, the Knowledge Link Corporation. Since this page cannot legibly accommodate all copyright notices, the acknowledgments constitute an extension of the copyright notice. While every effort has been made to ensure the reliability of the information presented in this publication, the Gale Group neither guarantees the accuracy of the data contained herein nor assumes any responsibility for errors, omissions or discrepancies. The Gale Group accepts no payment for listing, and inclusion in the publication of any organization, agency, institution, publication, service, or individual does not imply endorsement of the editor or publisher. Errors brought to the attention of the publisher and verified to the satisfaction of the publisher will be corrected in future editions. This book is printed on recycled paper that meets Environmental Protection Agency standards. The paper used in this publication meets the minimum requirements of American National Standard for Information Sciences-Permanence Paper for Printed Library Materials, ANSI Z39.48-1984. This publication is a creative work fully protected by all applicable copyright laws, as well as by misappropriation, trade secret, unfair competition, and other applicable laws. The authors and editor of this work have added value to the underlying factual material herein through one or more of the following: unique and original selection, coordination, expression, arrangement, and classification of the information. Gale Group and design is a trademark used herein under license. All rights to this publication will be vigorously defended. Copyright © 2002 Gale Group 27500 Drake Road Farmington Hills, MI 48331-3535 All rights reserved including the right of reproduction in whole or in part in any form. ISBN 0-7876-5609-7 (set) 0-7876-5610-0 (Vol. 1) 0-7876-5611-9 (Vol. 2) Printed in the United States of America 10 9 8 7 6 5 4 3 2 1 Library of Congress Cataloging-in-Publication Data The Gale encyclopedia of cancer / Ellen Thackery. p. cm. Includes bibliographical references and index. ISBN 0-7876-5610-0 (v. 1) — ISBN 0-7876-5611-9 (v.2) — ISBN 0-7876-5609-7 (set : hardcover) 1. Cancer—Encyclopedias. 2. Oncology—Encyclopedias. I. Thackery, Ellen, 1972RC254.5 .G353 2001 616.99'4'003—dc21 2001046015 CONTENTS Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IX Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XI Advisory Board . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XV Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XVII Illustrations of Body Systems . . . . . . . . . . . . . . . . . . . . XXI Entries Volume 1: A-K. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Volume 2: L-Z . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565 Appendices Appendix I: National Cancer Institute–Designated Comprehensive Cancer Centers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1155 Appendix II: National Support Groups . . . . . 1159 Appendix III: Government Agencies and Research Groups . . . . . . . . . . . . . . . . . . . . . . . . 1163 General Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1165 G A L E E N C Y C L O P E D I A O F CA N C E R V PLEASE READ—IMPORTANT INFORMATION The Gale Encyclopedia of Cancer is a medical reference product designed to inform and educate readers about a wide variety of cancers, treatments, diagnostic procedures, side effects, and cancer drugs. The Gale Group believes the product to be comprehensive, but not necessarily definitive. It is intended to supplement, not replace, consultation with a physician or other health care practitioner. While the Gale Group has made substantial efforts to provide information that is accurate, comprehensive, and up-to-date, the Gale Group makes no representations or warranties of any G A L E E N C Y C L O P E D I A O F CA N C E R kind, including without limitation, warranties of merchantability or fitness for a particular purpose, nor does it guarantee the accuracy, comprehensiveness, or timeliness of the information contained in this product. Readers should be aware that the universe of medical knowledge is constantly growing and changing, and that differences of medical opinion exist among authorities. Readers are also advised to seek professional diagnosis and treatment for any medical condition, and to discuss information obtained from this book with their health care provider. VII INTRODUCTION The Gale Encyclopedia of Cancer: A Guide to Cancer and Its Treatments is a unique and invaluable source of information for anyone touched by cancer. This collection of over 450 entries provides in-depth coverage of specific cancer types, diagnostic procedures, treatments, cancer side effects, and cancer drugs. In addition, entries have been included to facilitate understanding of common cancer-related concepts, such as cancer biology, carcinogenesis, and cancer genetics, as well as cancer issues such as clinical trials, home health care, fertility issues, and cancer prevention. This encyclopedia minimizes medical jargon and uses language that laypersons can understand, while still providing thorough coverage that will benefit health science students as well. Entries follow a standardized format that provides information at a glance. Rubrics include: Cancer types Cancer drugs Definition Description Demographics Causes and symptoms Diagnosis Treatment team Clinical staging, treatments, and prognosis Coping with cancer treatment Clinical trials Prevention Special concerns Resources Definition Purpose Description Recommended dosage Precautions Side effects Interactions INCLUSION CRITERIA A preliminary list of cancers and related topics was compiled from a wide variety of sources, including professional medical guides and textbooks, as well as consumer guides and encyclopedias. The advisory board, G A L E E N C Y C L O P E D I A O F CA N C E R made up of medical doctors and oncology pharmacists, evaluated the topics and made suggestions for inclusion. Final selection of topics to include was made by the advisory board in conjunction with the Gale editor. ABOUT THE CONTRIBUTORS The essays were compiled by experienced medical writers, including physicians, pharmacists, nurses, and other health care professionals. The advisors reviewed the completed essays to ensure that they are appropriate, up-to-date, and medically accurate. HOW TO USE THIS BOOK The Gale Encyclopedia of Cancer has been designed with ready reference in mind. • Straight alphabetical arrangement of topics allows users to locate information quickly. • Bold-faced terms within entries direct the reader to related articles. • Cross-references placed throughout the encyclopedia direct readers from alternate names and related topics to entries. • A list of key terms is provided where appropriate to define unfamiliar terms or concepts. • A list of questions to ask the doctor is provided whenever appropriate to help facilitate discussion with the patient's physician. • The Resources section for non-drug entries directs readers to additional sources of medical information on a topic. • Valuable contact information for organizations and support groups is included with each cancer type entry. Appendix II at the back of Volume II contains an extensive list of organizations arranged in alphabetical order. • A comprehensive general index guides readers to all topics mentioned in the text. IX Introduction • A note about drug entries: Drug entries are listed in alphabetical order by common generic names. However, because many oncology drugs have more than one common generic name, and because in many cases, the brand name is also often used interchangeably with a generic name, drugs can be located in one of three ways. The reader can: find the generic drug name in alphabetical order, be directed to the entry from an alternate name cross-reference, or use the index to look up a brand name, which will direct the reader to the equivalent generic name entry. If the reader would like more information about oncology drugs than these entries provide, the reader is encouraged to consult with a physician, pharmacist, or the reader may find helpful any one of a number of books about cancer drugs. Two that may be helpful are: D. Solimando's Drug Information Handbook for Oncology, or R. Ellerby's Quick Reference Handbook of Oncology Drugs. GRAPHICS The Gale Encyclopedia of Cancer contains over 200 full-color illustrations, photos and tables. Eleven illustrations of various body systems can be found in the front matter of the book, and these can help the reader to understand which cancers may affect which organs, and how the various systems interact. ACKNOWLEDGMENTS The editor would like to express appreciation to the following medical professionals who reviewed several entries within their areas of expertise for the Gale Encyclopedia of Cancer. X Linda Bressler, Pharm.D., B.C.O.P. Clinical Associate Professor College of Pharmacy University of Illinois Chicago, Illinois Susan M. Mockus, Ph.D Scientific Consultant Seattle, Washington James H. Morse, M.D. Assistant Professor Division of Gastroenterology University of Virginia Health Sciences Center Charlottesville, Virginia PHOTO ACKNOWLEDGMENTS On the cover, clockwise from upper left: Colored computed tomography (CT) scan of a human brain. (Dept. of Clinical Radiology, Salisbury District Hospital, Science Source/Photo Researchers. Reproduced by permission.) Color digitized image of the herpes simplex virus. (Custom Medical Stock Photo. Reproduced by permission.) Colored CT scan revealing cancer of the liver. (Dept. of Clinical Radiology, Salisbury District Hospital, Science Source/Photo Reseachers. Reproduced by permission.) False-color bone scan of the spine and ribs showing metastatic bone cancer of the spine. (CNRI, Science Source/Photo Researchers. Reproduced by permission.) G A L E E N C Y C L O P E D I A O F CA N C E R FOREWORD Unfortunately, man must suffer disease. Some diseases are totally reversible and can be effectively treated. Moreover, some diseases with proper treatment have been virtually annihilated, such as polio, rheumatic fever, smallpox, and, to some extent, tuberculosis. Other diseases seem to target one organ, such as the heart, and there has been great progress in either fixing defects, adding blood flow, or giving medications to strengthen the diseased pump. Cancer, however, continues to frustrate even the cleverest of doctors or the most fastidious of health conscious individuals. Why? By its very nature, cancer is a survivor. It has only one purpose: to proliferate. After all, that is the definition of cancer: unregulated growth of cells that fail to heed the message to stop growing. Normal cells go through a cycle of division, aging, and then selection for death. Cancer cells are able to circumvent this normal cycle, and escape recognition to be eliminated. There are many mechanisms that can contribute to this unregulated cell growth. One of these mechanisms is inheritance. Unfortunately, some individuals can be programmed for cancer due to inherited disorders in their genetic makeup. In its simplest terms, one can inherit a faulty gene or a missing gene whose role is to eliminate damaged cells or to prevent imperfect cells from growing. Without this natural braking system, the damaged cells can divide and lead to more damaged cells with the same abnormal genetic makeup as the parent cells. Given enough time, and our inability to detect them, these groups of cells can grow to a size that will cause discomfort or other symptoms. Inherited genetics are obviously not the only source of abnormalities in cells. Humans do not live in a sterile world devoid of environmental attacks or pathogens. Humans must work, and working environments can be dangerous. Danger can come in the form of radiation, chemicals, or fibers to which we may be chronically exposed with or without our knowledge. Moreover, man must eat, and if our food is contaminated with these environmental hazards, or if we prepare our food in a way G A L E E N C Y C L O P E D I A O F CA N C E R that may change the chemical nature of the food to hazardous molecules, then chronic exposure to these toxins could damage cells. Finally, man is social. He has found certain habits that are pleasing to him because they either relax him or release his inhibitions. Such habits, including smoking and alcohol consumption, can have a myriad of influences on the genetic makeup of cells. Why the emphasis on genes in the new century? Because they are potentially the reason as well as the answer for cancer. Genes regulate our micro- and macrosopic events by eventually coding for proteins that control our structure and function. If the above-mentioned environmental events cause errors in those genes that control growth, then imperfect cells can start to take root. For the majority of cases, a whole cascade of genetic events must occur before a cell is able to outlive its normal predecessors. This cascade of events could take years to occur, in a silent, undetected manner until the telltale signs and symptoms of advanced cancer are seen, including pain, lack of appetite, cough, loss of blood, or the detection of a lump. How did these cells get to this state where they are now dictating the everyday physical, psychological, and economic events for the person afflicted? At this time, the sequence of genetic catastrophes is much too complex to comprehend or summarize because, it is only in the past year that we have even been able to map what genes we have and where they are located in our chromosomes. We have learned, however, that cancer cells are equipped with a series of self-protection mechanisms. Some of the altered genes are actually able to express themselves more than in the normal situation. These genes could then code for more growth factors for the transforming cell, or they could make proteins that could keep our own immune system from eliminating these interlopers. Finally, these cells are chameleons: if we treat them with drugs to try to kill them, they can "change their colors" by mutation, and then be resistant to the drugs that may have harmed them before. Then what do we do for treatment? Man has always had a fascination with grooming, and grooming involves XI Foreword removal—dirt, hair, and waste. The ultimate removal involves cutting away the spoiled or imperfect portion. An abnormal growth? Remove it by surgery...make sure the edges are clean. Unfortunately, the painful reality of cancer surgery is that it is highly effective when performed in the early stages of the disease. "Early stages of the disease" implies that there is no spread, or, hopefully, before there are symptoms. In the majority of cases, however, surgery cannot eradicate all the disease because the cancer is not only at the primary site of the lump, but has spread to other organs. Cancer is not just a process of growth, but also a metastasizing process that allows for invasion and spread. The growing cells need nourishment so they secrete proteins that allow for the growth of blood vessels (angiogenesis); once the blood vessels are established from other blood vessels, the tumor cells can make proteins that will dissolve the imprisoning matrix surrounding them. Once this matrix is dissolved, it is only a matter of time before the cancer cells can migrate to other places making the use of surgery fruitless. Since cancer cells have a propensity to leave home and pay a visit to other organs, therapies must be geared to treat the whole body and not just the site of origin. The problem with these chemotherapies is that they are not selective and wreak havoc on tissues that are not affected by the cancer. These therapies are not natural to the human host, and result in nausea, loss of appetite, fatigue, as well as a depletion in our cells that protect us from infection and those that carry oxygen. Doctors who prescribe such medications walk a fine line between helping the patient (causing a "response" in the cancer by making it smaller) or causing "toxicity" which, due to effects on normal organs, causes the patient problems. Although these drugs are far from perfect, we are fortunate to have them because when they work, their results can be remarkable. But that's the problem—"when they work." We cannot predict who is going to benefit from our therapies, and doctors must inform the patient and his/her family about countless studies that have been done to validate the use of these potentially beneficial/potentially harmful agents. Patients must suffer the frustration that oncologists have because each individual afflicted with cancer is different, and indeed, each cancer is different. This makes it virtually impossible to personalize an individual's treatment expectations and life expectancy. Cancer, after all, is a very impersonal disease, and does not respect sex, race, wealth, age, or any other "human" characteristics. Cancer treatment is in search of "smart" options. Like modern-day instruments of war, successful cancer treatment will necessitate the construction of therapies that can do three basic tasks: search out the enemy, recognize the enemy, and kill the enemy without causing "friendly XII fire." The successful therapies of the future will involve the use of "living components," "manufactured components," or a combination of both. Living components, white blood cells, will be educated to recognize where the cancer is, and help our own immune system fight the foreign cells. These lymphocytes can be educated to recognize signals on the cancer cell which make them unique. Therapies in the future will be able to manufacture molecules with these signature, unique signals which are linked to other molecules specifically for killing the cells. Only the cancer cells are eliminated in this way, hopefully sparing the individual from toxicity. Why use these unique signals as delivery mechanisms? If they are unique and are important for growth of the cancer cell, it makes sense to target them directly. This describes the ambitious mission of gene therapy, whose goal is to supplement a deficient, necessary genetic pool or diminish the number of abnormally expressed genes fortifying the cancer cells. If a protein is not being made that slows the growth of cells, gene therapy would theoretically supply the gene for this protein to replenish it and cause the cells to slow down. If the cells can make their own growth factors that sustain them selectively over normal cells, then the goal is to block the production of this growth factor. There is no doubt that gene therapy is the wave of the future and is under intense investigation and scrutiny at present. The problem, however, is that there is no way to tell when this future promise will be fulfilled. No book can describe the medical, psychological, social, and economic burden of cancer, and if this is your first confrontation with the enemy, you may find yourself overwhelmed with its magnitude. Books are only part of the solution. Newly enlisted recruits in this war must seek proper counsel from educated physicians who will inform the family and the patient of the risks and benefits of a treatment course in a way that can be understood. Advocacy groups of dedicated volunteers, many of whom are cancer survivors, can guide and advise. The most important component, however, is an intensely personal one. The afflicted individual must realize that he/she is responsible for charting the course of his/her disease, and this requires the above described knowledge as well as great personal intuition. Cancer comes as a series of shocks: the symptoms, the diagnosis, and the treatment. These shocks can be followed by cautious optimism or profound disappointment. Each one of these shocks either reinforces or chips away at one's resolve, and how an individual reacts to these issues is as unique as the cancer that is being dealt with. While cancer is still life threatening, strides have been made in the fight against the disease. Thirty years ago, a young adult diagnosed with testicular cancer had few G A L E E N C Y C L O P E D I A O F CA N C E R G A L E E N C Y C L O P E D I A O F CA N C E R in cancer care will be when cancer is no longer thought of as a life-ending disease, but as a chronic disease whose symptoms can be managed. Anyone who has been touched by cancer or who has been involved in the fight against it lives in hope that that day will arrive. Helen A. Pass, M.D., F.A.C.S. Dr. Pass is the Director of the Breast Care Center at William Beaumont Hospital in Royal Oak, Michigan. XIII Foreword options for treatment that could result in cure. Now, chemotherapy for good risk Stage II and III testicular cancer can result in a complete response of the tumor in 98% of the cases and a durable response in 92%. Sixty years ago, there were no regimens that could cause a complete remission for a child diagnosed with leukemia; but now, using combination chemotherapy, complete remissions are possible in 96% of these cases. Progress has been made, but more progress is needed. The first real triumph ADVISORY BOARD A number of experts in the medical community provided invaluable assistance in the formulation of this encyclopedia. The advisory board performed a myriad of duties, from defining the scope of coverage to reviewing individual entries for accuracy and accessibility. The editor would like to express appreciation to them for their time and for their contributions. A. Richard Adrouny, M.D., F.A.C.P. Clinical Assistant Professor of Medicine Division of Oncology Stanford University Director of Medical Oncology Community Hospital of Los Gatos-Saratoga Los Gatos, California Elise D. Cook, M.D. Assistant Professor Principal Investigator, Selenium and Vitamin E Cancer Prevention Trial (SELECT) Clinical Cancer Prevention University of Texas M.D. Anderson Cancer Center Houston, Texas Susan Miesfeldt, M.D. Associate Professor of Internal Medicine Division of Hematology and Oncology University of Virginia Health System Charlottesville, Virginia Ralph M. Myerson, M.D., F.A.C.P. Clinical Professor of Medicine Medical College of Pennsylvania–Hahnemann University Philadelphia, Pennsylvania Helen A. Pass, M.D., F.A.C.S. Director, Breast Care Center William Beaumont Hospital Royal Oak, Michigan Peter S. Edelstein, M.D., F.A.C.S., F.A.S.C.R.S. Chief Medical Officer and Vice President Novasys Medical, Inc. Sunnyvale, California Trinh Pham, Pharm.D. Assistant Clinical Professor University of Connecticut, School of Pharmacy New Haven, Connecticut Chul-Hoon Kwon, Ph.D. Professor College of Pharmacy and Allied Health Professions St. John's University Jamaica, New York J. Andrew Skirvin, Pharm.D., B.C.O.P. Assistant Clinical Professor College of Pharmacy and Allied Health Professions St. John's University Jamaica, New York G A L E E N C Y C L O P E D I A O F CA N C E R XV CONTRIBUTORS Margaret Alic, Ph.D. Science Writer Eastsound, Washington Cheryl Branche, M.D. Retired General Practitioner Jackson, Mississippi Lori De Milto Medical Writer Sicklerville, New York Lisa Andres, M.S., C.G.C. Certified Genetic Counselor and Medical Writer San Jose, California Tamara Brown, R.N. Medical Writer Boston, Massachusetts Stefanie B. N. Dugan, M.S. Genetic Counselor Milwaukee, Wisconsin Racquel Baert, M.Sc. Medical Writer Winnipeg, Canada Diane M. Calabrese Medical Sciences and Technology Writer Silver Spring, Maryland Janis O. Flores Medical Writer Sebastopol, California Julia R. Barrett Science Writer Madison, Wisconsin Rosalyn Carson-DeWitt, M.D. Durham, North Carolina Nancy J. Beaulieu, RPh., B.C.O.P. Oncology Pharmacist New Haven, Connecticut Linda K. Bennington, C.N.S., M.S.N. Clinical Nurse Specialist Department of Nursing Old Dominion University Norfolk, Virginia Kenneth J. Berniker, M.D. Attending Physician Emergency Department Kaiser Permanente Medical Center Vallejo, California Olga Bessmertny, Pharm.D. Clinical Pharmacy Manager Pediatric Hematology/Oncology/ Bone Marrow Transplant Children's Hospital of New York Columbia Presbyterian Medical Center New York, New York Patricia L. Bounds, Ph.D. Science Writer Zürich, Switzerland G A L E E N C Y C L O P E D I A O F CA N C E R Lata Cherath, Ph.D. Science Writer Franklin Park, New York Lisa Christenson, Ph.D. Science Writer Hamden, Connecticut Rhonda Cloos, R.N. Medical Writer Austin, Texas David Cramer, M.D. Medical Writer Chicago, Illinois Tish Davidson, A.M. Medical Writer Fremont, California Dominic De Bellis, Ph.D. Medical Writer/Editor Mahopac, New York Tiffani A. DeMarco, M.S. Genetic Counselor Cancer Control Georgetown University Washington, DC Paula Ford-Martin Medical Writer Chaplin, Minnesota Rebecca J. Frey, Ph.D. Research and Administrative Associate East Rock Institute New Haven, Connecticut Jill Granger, M.S. Senior Research Associate University of Michigan Ann Arbor, Michigan David E. Greenberg, M.D. Medicine Resident Baylor College of Medicine Houston, Texas Maureen Haggerty Medical Writer Ambler, Pennsylvania Kevin Hwang, M.D. Medical Writer Morristown, New Jersey Michelle L. Johnson, M.S., J.D. Patent Attorney and Medical Writer Portland, Oregon Paul A. Johnson, Ed.M. Medical Writer San Diego, California XVII Contributors Cindy L. A. Jones, Ph.D. Biomedical Writer Sagescript Communications Lakewood, Colorado Crystal H. Kaczkowski, M.Sc. Medical Writer Montreal, Canada David S. Kaminstein, M.D. Medical Writer Westchester, Pennsylvania Beth Kapes Medical Writer Bay Village, Ohio Bob Kirsch Medical Writer Ossining, New York Melissa Knopper Medical Writer Chicago, Illinois Monique Laberge, Ph.D. Research Associate Department of Biochemistry and Biophysics University of Pennsylvania Philadelphia, Pennsylvania Jill S. Lasker Medical Writer Midlothian, Virginia G. Victor Leipzig, Ph.D. Biological Consultant Huntington Beach, California Lorraine Lica, Ph.D. Medical Writer San Diego, California John T. Lohr, Ph.D. Utah State University Logan, Utah Warren Maltzman, Ph.D. Consultant, Molecular Pathology Demarest, New Jersey Richard A. McCartney M.D. Fellow, American College of Surgeons Diplomat, American Board of Surgery Richland, Washington XVIII Sally C. McFarlane-Parrott Medical Writer Mason, Michigan Toni Rizzo Medical Writer Salt Lake City, Utah Monica McGee, M.S. Science Writer Wilmington, North Carolina Martha Floberg Robbins Medical Writer Evanston, Illinois Alison McTavish, M.Sc. Medical Writer and Editor Montreal, Quebec Richard Robinson Medical Writer Tucson, Arizona Molly Metzler, R.N., B.S.N. Registered Nurse, Medical Writer Seaford, Delaware Edward R. Rosick, D.O., M.P.H., M.S. University Physician, Clinical Assistant Professor Student Health Services The Pennsylvania State University University Park, Pennsylvania Beverly G. Miller MT(ASCP), Technical Writer Charlotte, North Carolina Mark A. Mitchell, M.D. Medical Writer Seattle, Washington Laura J. Ninger Medical Writer Weehawken, New Jersey Nancy J. Nordenson Medical Writer Minneapolis, Minnesota Teresa G. Norris, R.N. Medical Writer Ute Park, New Mexico Melinda Granger Oberleitner, R.N., D.N.S. Acting Department Head and Associate Professor Department of Nursing University of Louisiana at Lafayette Lafayette, Louisiana J. Ricker Polsdorfer, M.D. Medical Writer Phoenix, Arizona Elizabeth J. Pulcini, M.S. Medical Writer Phoenix, Arizona Kulbir Rangi, D.O. Medical Doctor and Writer New York, New York Esther Csapo Rastegari, Ed.M., R.N., B.S.N. Registered Nurse, Medical Writer Holbrook, Masachusetts Nancy Ross-Flanigan Science Writer Belleville, Michigan Belinda Rowland, Ph.D. Medical Writer Voorheesville, New York Andrea Ruskin, M.D. Whittingham Cancer Center Norwalk, Connecticut Laura Ruth, Ph.D. Medical, Science, & Technology Writer Los Angeles, California Kausalya Santhanam, Ph.D. Technical Writer Branford, Connecticut Marc Scanio Doctoral Candidate in Chemistry Stanford University Stanford, California Joan Schonbeck, R.N. Medical Writer Nursing Massachusetts Department of Mental Health Marlborough, Massachusetts Kristen Mahoney Shannon, M.S., C.G.C. Genetic Counselor Center for Cancer Risk Analysis Massachusetts General Hospital Boston, Massachusetts G A L E E N C Y C L O P E D I A O F CA N C E R Deanna M. Swartout-Corbeil Registered Nurse, Freelance Writer Thompsons Station, Tennessee Anna Rovid Spickler, D.V.M., Ph.D. Medical Writer Salisbury, Maryland Jane M. Taylor-Jones, M.S. Research Associate Donald W. Reynolds Department of Geriatrics University of Arkansas for Medical Sciences Little Rock, Arkansas Laura L. Stein, M.S. Certified Genetic Counselor Familial Cancer ProgramDepartment of Hematology/ Oncology Dartmouth Hitchcock Medical Center Lebanon, New Hampshire Phyllis M. Stein, B.S., C.C.R.P. Affiliate Coordinator Grand Rapids Clinical Oncology Program Grand Rapids, Michigan Kurt Sternlof Science Writer New Rochelle, New York G A L E E N C Y C L O P E D I A O F CA N C E R Carol Turkington Medical Writer Lancaster, Pennsylvania Marianne Vahey, M.D. Clinical Instructor Medicine Yale University School of Medicine New Haven, Connecticut Malini Vashishtha, Ph.D. Medical Writer Irvine, California Ellen S. Weber, M.S.N. Medical Writer Contributors Genevieve Slomski, Ph.D. Medical Writer New Britain, Connecticut Fort Wayne, Indiana Barbara Wexler, M.P.H. Medical Writer Chatsworth, California Wendy Wippel, M.Sc. Medical Writer and Adjunct Professor of Biology Northwest Community College Hernando, Mississippi Debra Wood, R.N. Medical Writer Orlando, Florida Kathleen D. Wright, R.N. Medical Writer Delmar, Delaware Jon Zonderman Medical Writer Orange, California Michael V. Zuck, Ph.D. Writer Boulder, Colorado XIX Skeleton HUMAN SKELETON and SKIN. Some cancers that affect the SKELETON are: Osteosarcoma; Ewing's sarcoma; Fibrosarcoma (can also be found in soft tissues like muscle, fat, connective tissues, etc.). Some cancers that affect tissue near bones: Chondrosarcoma (affects joints near bones); Rhabdomyosarcoma (formed from cells of muscles attached to bones); Malignant fibrous histiocytoma (common in soft tissues, rare in bones). SKIN CANCERS: Basal cell carcinoma; Melanoma; Merkel cell carcinoma; Squamous cell carcinoma of the skin; and Trichilemmal carcinoma. Precancerous skin condition: Bowen's disease. Lymphomas that affect the skin: Mycosis fungoides; Sézary syndrome. (Illustration provided by Argosy Publishing.) G A L E E N C Y C L O P E D I A O F CA N C E R XXI Circulatory system HUMAN CIRCULATORY SYSTEM. Some cancers of the blood cells are: Acute erythroblastic leukemia; Acute lymphocytic leukemia; Acute myelocytic leukemia; Chronic lymphocytic leukemia; Chronic myelocytic leukemia; Hairy cell leukemia; and Multiple myeloma. One condition associated with various cancers that affects blood is called Myelofibrosis. (Illustration provided by Argosy Publishing.) XXII G A L E E N C Y C L O P E D I A O F CA N C E R Nervous system HUMAN NERVOUS SYSTEM. Some brain and central nervous system tumors are: Astrocytoma; Carcinomatous meningitis; Central nervous system carcinoma; Central nervous system lymphoma; Chordoma; Choroid plexus tumors; Craniopharyngioma; Ependymoma; Medulloblastoma; Meningioma; Oligodendroglioma; and Spinal axis tumors. One kind of noncancerous growth in the brain: Acoustic neuroma. (Illustration provided by Argosy Publishing.) G A L E E N C Y C L O P E D I A O F CA N C E R XXIII Lymphatic system HUMAN LYMPHATIC SYSTEM. The lymphatic system and lymph nodes are shown here in pale green, the thymus in deep blue, and one of the bones rich in bone marrow (the femur) is shown here in purple. Some cancers of the lymphatic system are: Burkitt's lymphoma; Cutaneous T-cell lymphoma; Hodgkin's disease; MALT lymphoma; Mantle cell lymphoma; Sézary syndrome; and Waldenström's macroglobulinemia. (Illustration provided by Argosy Publishing.) XXIV G A L E E N C Y C L O P E D I A O F CA N C E R Digestive system HUMAN DIGESTIVE SYSTEM. Organs and cancers of the digestive system include: Salivary glands (shown in turquoise): Salivary gland tumors. Esophagus (shown in bright yellow): Esophageal cancer. Liver (shown in bright red): Bile duct cancer; Liver cancer. Stomach (pale gray-blue): Stomach cancer. Gallbladder (bright orange against the red liver): Gallbladder cancer. Colon (green): Colon cancer. Small intestine (purple): Small intestinal cancer; can have malignant tumors associated with Zollinger-Ellison syndrome. Rectum (shown in pink, continuing the colon): Rectal cancer. Anus (dark blue): Anal cancer. (Illustration provided by Argosy Publishing.) G A L E E N C Y C L O P E D I A O F CA N C E R XXV Head and neck HEAD AND NECK. The pharynx, the passage that leads from the nostrils down through the neck is shown in orange. This passage is broken into several divisions. The area posterior to (behind) the nose is the nasopharynx. The area posterior to the mouth is the oropharynx. The oropharynx leads into the laryngopharynx, which opens into the esophagus (still in orange) and the larynx (shown in the large image in medium blue). Each of these regions may be affected by cancer, and the cancers include: Nasopharyngeal cancer; Oropharyngeal cancer; Esophageal cancer; and Laryngeal cancer. Oral cancers can affect the lips, gums, and tongue (pink). Referring to the smaller, inset picture of the salivary glands, salivary gland tumors can affect the parotid glands (shown here in yellow), the submandibular glands (inset picture, turquoise), and the sublingual glands (purple). (Illustration provided by Argosy Publishing.) XXVI G A L E E N C Y C L O P E D I A O F CA N C E R Endocrine system HUMAN ENDOCRINE SYSTEM. The glands and cancers of the endocrine system include: In the brain: the pituitary gland shown in blue (pituitary tumors), the hypothalamus in pale green, and the pineal gland in bright yellow. Throughout the rest of the body: Thyroid (shown in dark blue): Thyroid cancer. Parathyroid glands, four of them adjacent to the thyroid: Parathyroid cancer. Thymus (green): Thymic cancer; Thymoma. Pancreas (turquoise): Pancreatic cancer, endocrine; Pancreatic cancer, exocrine; Zollinger-Ellison syndrome tumors can be malignant and can be found in the pancreas. Adrenal glands (shown in apricot, above the kidneys): Neuroblastoma often originates in these glands; Pheochromocytoma tumors are often found in adrenal glands. Testes (in males, shown in yellow): Testicular cancer. Ovaries (in females, shown in dark blue in inset image): Ovarian cancer. (Illustration provided by Argosy Publishing.) G A L E E N C Y C L O P E D I A O F CA N C E R XXVII Respiratory system HUMAN RESPIRATORY SYSTEM. Air is breathed in through nose or mouth, enters the pharynx, shown here in orange, and passes through the larynx, shown here as a green tube with a ridged texture. (The smooth green tube shown is the esophagus, which is posterior to the larynx and which is involved in digestion instead of breathing.) The air then passes into the trachea (purple), a tube that divides into two tubes called bronchi. One bronchus passes into each lung, and continues to branch within the lung. These branches are called bronchioles and each bronchiole leads to a tiny cluster of air sacs called alveoli, where the exchange of gases occurs, so that the air and gases breathed in get diffused to the blood. The lungs (deep blue) are spongy and have lobes and can be affected by Lung cancer, both the non-small cell and small-cell types. (Illustration provided by Argosy Publishing.) XXVIII G A L E E N C Y C L O P E D I A O F CA N C E R Urinary system HUMAN URINARY SYSTEM. Organs and cancers of the urinary system include: Kidneys (shown in purple): Kidney cancer; Renal pelvis tumors; Wilms' tumor. Ureters are shown in green. Bladder (blue-green): Bladder cancer. The kidneys, bladder, or ureters can be affected by a cancer type called Transitional cell carcinoma. (Illustration provided by Argosy Publishing.) G A L E E N C Y C L O P E D I A O F CA N C E R XXIX Female reproductive system FEMALE REPRODUCTIVE SYSTEM. Organs and cancers of the female reproductive system include: Uterus, shown in red with the uterine or Fallopian tubes: Endometrial cancer. Ovaries (blue): Ovarian cancer. Vagina (shown in pink with a yellow interior or lining): Vaginal cancer. Breasts: Breast cancer; Paget's disease of the breast. Shown in detailed inset only in turquoise, Cervix: Cervical cancer. (Illustration provided by Argosy Publishing.) XXX G A L E E N C Y C L O P E D I A O F CA N C E R Male reproductive system MALE REPRODCTIVE SYSTEM. Organs, glands, and cancers of the male reproductive system include: Penis (shown in pink): Penile cancer. Testes (shown in yellow): Testicular cancer. Prostate gland (shown in full-body illustration in a peach/ apricot color, and in the inset as the dark blue gland between the bladder and the penis): Prostate cancer. (Illustration provided by Argosy Publishing.) G A L E E N C Y C L O P E D I A O F CA N C E R XXXI A 2-CdA see Cladribine 5-Azacitidine see Azacitidine 5-Fluorouracil see Fluorouracil 6-Mercaptopurine see Mercaptopurine 6-Thioguanine see Thioguanine Acoustic neuroma Definition An acoustic neuroma is a benign tumor involving cells of the myelin sheath that surrounds the vestibulocochlear nerve (eighth cranial nerve). Description The vestibulocochlear nerve extends from the inner ear to the brain and is made up of a vestibular branch, often called the vestibular nerve, and a cochlear branch, called the cochlear nerve. The vestibular and cochlear nerves lie next to one another. They also run along side other cranial nerves. People possess two of each type of vestibulocochlear nerve, one that extends from the left ear and one that extends from the right ear. The vestibular nerve transmits information concerning balance from the inner ear to the brain and the cochlear nerve transmits information about hearing. The vestibular nerve, like many nerves, is surrounded by a cover called a myelin sheath. A tumor, called a schwannoma, can sometimes develop from the cells of the myelin sheath. A tumor is an abnormal growth of tissue that results from the uncontrolled growth of cells. Acoustic neuromas are often called vestibular schwannomas because they are tumors that arise from the myelin sheath that surrounds the vestibular nerve. Acoustic neuromas are considered benign (non-cancerous) tumors G A L E E N C Y C L O P E D I A O F CA N C E R since they do not spread to other parts of the body. They can occur anywhere along the vestibular nerve but are most likely to occur where the vestibulocochlear nerve passes through the tiny bony canal that connects the brain and the inner ear. An acoustic neuroma can arise from the left vestibular nerve or the right vestibular nerve. A unilateral tumor is a tumor arising from one nerve and a bilateral tumor arises from both vestibular nerves. Unilateral acoustic neuromas usually occur spontaneously (by chance). Bilateral acoustic neuromas occur as part of a hereditary condition called Neurofibromatosis Type 2 (NF2). A person with NF2 has inherited a predisposition for developing acoustic neuromas and other tumors of the nerve cells. Acoustic neuromas usually grow slowly and can take years to develop. Some acoustic neuromas remain so small that they do not cause any symptoms. As the acoustic neuroma grows it can interfere with the functioning of the vestibular nerve and can cause vertigo and balance difficulties. If the acoustic nerve grows large enough to press against the cochlear nerve, then hearing loss and a ringing (tinnitus) in the affected ear will usually occur. If untreated and the acoustic neuroma continues to grow, it can press against other nerves in the region and cause other symptoms. This tumor can be life threatening if it becomes large enough to press against and interfere with the functioning of the brain. Causes and symptoms Causes An acoustic neuroma is caused by a change or absence of both of the NF2 tumor suppressor genes in a nerve cell. Every person possesses a pair of NF2 genes in every cell of their body including their nerve cells. One NF2 gene is inherited from the egg cell of the mother and one NF2 gene is inherited from the sperm cell of the father. The NF2 gene is responsible for helping to prevent the formation of tumors in the nerve cells. In particular the NF2 gene helps to prevent acoustic neuromas. 1 Acoustic neuroma age of onset of acoustic neuroma in NF2 is 31 years of age versus 50 years of age for sporadic acoustic neuromas. Not all people with NF2, however, develop acoustic neuromas. People with NF2 are at increased risk for developing cataracts and tumors in other nerve cells. False-color magnetic resonance image (MRI) scan of a coronal section of the head & brain of someone suffering from an acoustic neuroma (green circular area). (Photograph by Mehau Kulyk, Photo Researchers, Inc. Reproduced by permission.) Only one unchanged and functioning NF2 gene is necessary to prevent the formation of an acoustic neuroma. If both NF2 genes become changed or missing in one of the myelin sheath cells of the vestibular nerve, then an acoustic neuroma will usually develop. Most unilateral acoustic neuromas result when the NF2 genes become spontaneously changed or missing. Someone with a unilateral acoustic neuroma that has developed spontaneously is not at increased risk for having children with an acoustic neuroma. Some unilateral acoustic neuromas result from the hereditary condition NF2. It is also possible that some unilateral acoustic neuromas may be caused by changes in other genes responsible for preventing the formation of tumors. Bilateral acoustic neuromas result when someone is affected with the hereditary condition NF2. A person with NF2 is typically born with one unchanged and one changed or missing NF2 gene in every cell of their body. Sometimes they inherit this change from their mother or father. Sometimes the change occurs spontaneously when the egg and sperm come together to form the first cell of the baby. The children of a person with NF2 have a 50% chance of inheriting the changed or missing NF2 gene. A person with NF2 will develop an acoustic neuroma if the remaining unchanged NF2 gene becomes spontaneously changed or missing in one of the myelin sheath cells of their vestibular nerve. People with NF2 often develop acoustic neuromas at a younger age. The mean 2 Most people with a unilateral acoustic neuroma are not affected with NF2. Some people with NF2, however, only develop a tumor in one of the vestibulocochlear nerves. Others may initially be diagnosed with a unilateral tumor but may develop a tumor in the other nerve a number of years later. NF2 should be considered in someone under the age of 40 who has a unilateral acoustic neuroma. Someone with a unilateral acoustic neuroma and other family members diagnosed with NF2 probably is affected with NF2. Someone with a unilateral acoustic neuroma and other symptoms of NF2 such as cataracts and other tumors may also be affected with NF2. On the other hand, someone over the age of 50 with a unilateral acoustic neuroma, no other tumors and no family history of NF2 is very unlikely to be affected with NF2. Symptoms Small acoustic neuromas usually only interfere with the functioning of the vestibulocochlear nerve. The most common first symptom of an acoustic neuroma is hearing loss, which is often accompanied by a ringing sound (tinnitis). People with acoustic neuromas sometimes report difficulties in using the phone and difficulties in perceiving the tone of a musical instrument or sound even when their hearing appears to be otherwise normal. In most cases the hearing loss is initially subtle and worsens gradually over time until deafness occurs in the affected ear. In approximately 10% of cases the hearing loss is sudden and severe. Acoustic neuromas can also affect the functioning of the vestibular branch of the vestibulocochlear nerve and van cause vertigo and dysequilibrium. Twenty percent of small tumors are associated with periodic vertigo, which is characterized by dizziness or a whirling sensation. Larger acoustic neuromas are less likely to cause vertigo but more likely to cause dysequilibrium. Dysequilibrium, which is characterized by minor clumsiness and a general feeling of instability, occurs in nearly 50% of people with an acoustic neuroma. As the tumor grows larger it can press on the surrounding cranial nerves. Compression of the fifth cranial nerve can result in facial pain and or numbness. Compression of the seventh cranial nerve can cause spasms, weakness or paralysis of the facial muscles. Double vision is a rare symptom but can result when the sixth cranial nerve is affected. Swallowing and/or speaking G A L E E N C Y C L O P E D I A O F CA N C E R If left untreated, the tumor can become large enough to press against and affect the functioning of the brain stem. The brain stem is the stalk-like portion of the brain that joins the spinal cord to the cerebrum, the thinking and reasoning part of the brain. Different parts of the brainstem have different functions such as the control of breathing and muscle coordination. Large tumors that impact the brain stem can result in headaches, walking difficulties (gait ataxia) and involuntary shaking movements of the muscles (tremors). In rare cases when an acoustic neuroma remains undiagnosed and untreated it can cause nausea, vomiting, lethargy and eventually coma, respiratory difficulties and death. In the vast majority of cases, however, the tumor is discovered and treated long before it is large enough to cause such serious manifestations. Diagnosis Anyone with symptoms of hearing loss should undergo hearing evaluations. Pure tone and speech audiometry are two screening tests that are often used to evaluate hearing. Pure tone audiometry tests to see how well someone can hear tones of different volume and pitch and speech audiometry tests to see how well someone can hear and recognize speech. An acoustic neuroma is suspected in someone with unilateral hearing loss or hearing loss that is less severe in one ear than the other ear (asymmetrical). Sometimes an auditory brainstem response (ABR, BAER) test is performed to help establish whether someone is likely to have an acoustic neuroma. During the ABR examination, a harmless electrical impulse is passed from the inner ear to the brainstem. An acoustic neuroma can interfere with the passage of this electrical impulse and this interference can, sometimes be identified through the ABR evaluation. A normal ABR examination does not rule out the possibility of an acoustic neuroma. An abnormal ABR examination increases the likelihood that an acoustic neuroma is present but other tests are necessary to confirm the presence of a tumor. If an acoustic neuroma is strongly suspected then magnetic resonance imaging (MRI) is usually performed. The MRI is a very accurate evaluation that is able to detect nearly 100% of acoustic neuromas. Computed tomography (CT scan, CAT scan)is unable to identify smaller tumors; but it can be used when an acoustic neuroma is suspected and an MRI evaluation cannot be performed. KEY TERMS Benign tumor—A localized overgrowth of cells that does not spread to other parts of the body. Chromosome—A microscopic structure, made of a complex of proteins and DNA, that is found within each cell of the body. Cranial nerves—The set of twelve nerves found on each side of the head and neck that control the sensory and muscle functions of a number of organs such as the eyes, nose, tongue face and throat. Computed tomography (CT)—An examination that uses a computer to compile and analyze the images produced by x rays projected at a particular part of the body. DNA testing—Testing for a change or changes in a gene or genes. Gene—A building block of inheritance, made up of a compound called DNA (deoxyribonucleic acid) and containing the instructions for the production of a particular protein. Each gene is found on a specific location on a chromosome. Magnetic resonance imaging (MRI)—A test which uses an external magnetic field instead of x rays to visualize different tissues of the body. Myelin sheath—The cover that surrounds many nerve cells and helps to increase the speed by which information travels along the nerve. Neurofibromatosis type 2 (NF2)—A hereditary condition associated with an increased risk of bilateral acoustic neuromas, other nerve cell tumors and cataracts. Protein—A substance produced by a gene that is involved in creating the traits of the human body such as hair and eye color or is involved in controlling the basic functions of the human body. Schwannoma—A tumor derived from the cells of the myelin sheath that surrounds many nerve cells. Tinnitus—A ringing sound or other noise in the ear. Vertigo—A feeling of spinning or whirling. Vestibulocochlear nerve (Eighth cranial nerve)— Nerve that transmits information, about hearing and balance from the ear to the brain. Once an acoustic neuroma is diagnosed, an evaluation by genetic specialists such as a geneticist and genetic G A L E E N C Y C L O P E D I A O F CA N C E R 3 Acoustic neuroma difficulties can occur if the tumor presses against the ninth, tenth, or twelfth cranial nerves. Acoustic neuroma counselor may be recommended. The purpose of this evaluation is to obtain a detailed family history and check for signs of NF2. If NF2 is strongly suspected then DNA testing may be recommended. DNA testing involves checking the blood cells obtained from a routine blood draw for the common gene changes associated with NF2. Treatment The three treatment options for acoustic neuroma are surgery, radiation, and observation. The physician and patient should discuss the pros and cons of the different options prior to making a decision about treatment. The patient's physical health, age, symptoms, tumor size, and tumor location should be considered. Microsurgery The surgical removal of the tumor or tumors is the most common treatment for acoustic neuroma. In most cases the entire tumor is removed during the surgery. If the tumor is large and causing significant symptoms, yet there is a need to preserve hearing in that ear, then only part of the tumor may be removed. During the procedure the tumor is removed under microscopic guidance and general anesthetic. Monitoring of the neighboring cranial nerves is done during the procedure so that damage to these nerves can be prevented. If preservation of hearing is a possibility, then monitoring of hearing will also take place during the surgery. Most people stay in the hospital four to seven days following the surgery. Total recovery usually takes four to six weeks. Most people experience fatigue and head discomfort following the surgery. Problems with balance and head and neck stiffness are also common. The mortality rate of this type of surgery is less than 2% at most major centers. Approximately 20% of patients experience some degree of post-surgical complications. In most cases these complications can be managed successfully and do not result in long-term medical problems. Surgery brings with it a risk of stroke, damage to the brain stem, infection, leakage of spinal fluid and damage to the cranial nerves. Hearing loss and/or tinnitis often result from the surgery. A follow-up MRI is recommended one to five years following the surgery because of possible regrowth of the tumor. Stereotactic radiation therapy During stereotactic radiation therapy, also called radiosurgery or radiotherapy, many small beams of radiation are aimed directly at the acoustic neuroma. The radiation is administered in a single large dose, under local anesthetic and is performed on an outpatient basis. This 4 results in a high dose of radiation to the tumor but little radiation exposure to the surrounding area. This treatment approach is limited to small or medium tumors. The goal of the therapy is to cause tumor shrinkage or at least limit the growth of the tumor. The long-term efficacy and risks of this treatment approach are not known. Periodic MRI monitoring throughout the life of the patient is therefore recommended. Radiation therapy can cause hearing loss which can sometimes occurs even years later. Radiation therapy can also cause damage to neighboring cranial nerves, which can result in symptoms such as numbness, pain or paralysis of the facial muscles. In many cases these symptoms are temporary. Radiation treatment can also induce the formation of other benign or malignant schwannomas. This type of treatment may therefore be contraindicated in the treatment of acoustic neuromas in those with NF2 who are predisposed to developing schwannomas and other tumors. Observation Acoustic neuromas are usually slow growing and in some cases they will stop growing and even become smaller or disappear entirely. It may therefore be appropriate in some cases to hold off on treatment and to periodically monitor the tumor through MRI evaluations. Long-term observation may be appropriate for example in an elderly person with a small acoustic neuroma and few symptoms. Periodic observation may also be indicated for someone with a small and asymptomatic acoustic neuroma that was detected through an evaluation for another medical problem. Observation may also be suggested for someone with an acoustic neuroma in the only hearing ear or in the ear that has better hearing. The danger of an observational approach is that as the tumor grows larger it can become more difficult to treat. Prognosis The prognosis for someone with a unilateral acoustic neuroma is usually quite good provided the tumor is diagnosed early and appropriate treatment is instituted. Long-term hearing loss and tinnitis in the affected ear are common, even if appropriate treatment is provided. Regrowth of the tumor is also a possibility following surgery or radiation therapy and repeat treatment may be necessary. The prognosis can be poorer for those with NF2 who have an increased risk of bilateral acoustic neuromas and other tumors. Resources BOOKS Filipo, R., and Barbara Maurizio Acoustic neuroma: trends and controversies: proceedings of the Symposium Acoustic G A L E E N C Y C L O P E D I A O F CA N C E R PERIODICALS Broad, R. W. "Management of Acoustic Neuroma." In New England Journal of Medicine. 340(14) (8 April 1999):1119. Lederman G, E. Arbit, and J. Lowry. "Management of Acoustic Neuroma." New England Journal of Medicine. 340(14) (8 April 1999):1119–1120. Levo H., I. Pyykko, and G. Blomstedt. "Non-surgical Treatment of Vestibular Schwannoma Patients." Acta OtoLaryngologica 529 (1997): 56–8. O'Donoghue G.M., T. Nikolopoulos and J. Thomsen. "Management of Acoustic Neuroma." In New England Journal of Medicine 340(14) (8 April 1999):1120–1121. Rigby, P. L., et al. "Acoustic Neuroma Surgery: Outcome Analysis of Patient-Perceived Disability." In American Journal of Otology 18 (July 1997): 427–35. van Roijen, L., et al. "Costs and Effects of Microsurgery versus Radiosurgery in Treating Acoustic Neuroma." In Acta Neurochirurgica 139 (1997): 942–48. Acute erythroblastic leukemia Definition Acute erythroblastic leukemia, also called erythremic myelosis, DiGuglielmo syndrome, or erythroleukemia, results from uncontrolled proliferation of immature erythrocytes (red blood cells). Description Acute erythroblastic leukemia, a variant of acute myelocytic leukemia, originates in the blood and in the bone marrow. In this form of leukemia, a large number of abnormal, immature red blood cells are produced. The advanced phase is also called the blast crisis. At this stage, over 50% of the cells in the bone marrow are immature malignant cells (also called blast cells or promelocytes). Demographics There are no statistics available for this rare form of cancer. Causes and symptoms ORGANIZATIONS Acoustic Neuroma Association. 600 Peachtree Pkwy, Suite 108, Cumming, GA 30041-6899. Phone:(770) 205-8211. Fax: (770) 205-0239. email@example.com <http://anausa. org> 28 June 2001. Acoustic Neuroma Association of Canada Box 369, Edmonton, AB T5J 2J6. 1-800-561-ANAC(2622). (780)428-3384. firstname.lastname@example.com. <http://www.anac.ca> 28 June 2001. British Acoustic Neuroma Association. Oak House, Ransom Wood Business Park, Southwell Road West, Mansfield, Nottingham, NG21 0HJ. Tel: 01623 632143. Fax: 01623 635313. firstname.lastname@example.com. <http://www.ukan.co.uk/ bana> 28 June 2001. Seattle Acoustic Neuroma Group. firstname.lastname@example.com <http://acousticneuromaseattle.org/entryenglish.html> 28 June 2001. OTHER University of California at San Francisco (UCSF)Information on Acoustic Neuromas <http://itsa.ucsf.edu/~rkj/IndexAN. html> (18 March 1998). 28 June 2001. National Institute of Health Consensus Statement OnlineAcoustic Neuroma 9(4)(11-13 December 1991). 28 June 2001. <http://text.nlm.nih.gov/nih/cdc/www/87txt.html> The causes of acute erythroblastic leukemia are largely unknown. However, acute erythroblastic leukemia constitutes 10–20% of leukemias secondary to radiation, alkylator therapy, or overexposure to benzene. Patients with this type of leukemia have less than the normal amount of healthy red blood cells and platelets, which results in insufficient amounts of oxygen being carried through the body. This condition is called anemia, and causes patients to experience severe weakness and tiredness. Patients may have less than the normal number of white blood cells as well. Other symptoms include fever, chills, loss of appetite and weight, easy bleeding or bruising (due to lower than normal platelet levels), bone or joint pain, headaches, vomiting, and confusion. In addition, patients with leukemia may have hepatosplenomegaly, an enlargement of the liver and spleen. Enlargement of these organs is noticed as a fullness or swelling in the abdomen, and can be felt by a doctor during a physical examination. The occurrence of Sweet's syndrome, a rare skin disorder accompanied by fever, inflammation of the joints (arthritis), and the sudden onset of a rash, has also been associated with acute erythroblastic leukemia. Lisa Andres, M.S., CGC Acquired Immune Deficiency syndrome see AIDS-related cancers Actinomycin D see Dactinomycin G A L E E N C Y C L O P E D I A O F CA N C E R Diagnosis Patients seeking treatment usually report a vague history of chronic general fatigue. Blood tests are used to establish the diagnosis. A sample of blood is examined 5 Acute erythroblastic leukemia Neuroma: Trends and Controversies, Rome, Italy, November 13–15, 1997. The Hague, Netherlands: Kugler,1999. Malis, Leonard Acoustic Neuroma New York: Elsevier, 1998. Roland, Peter, and Bradley Marple.Diagnosis and Management of Acoustic Neuroma (Sipac). Alexandria, VA: American Academy of Otolaryngology—Head and Neck Survey Foundation, 1998. Acute erythroblastic leukemia KEY TERMS Allogeneic bone marrow transplant—A bone marrow transplant using bone marrow obtained from a genetically matched healthy donor, such as a sister or a brother. Autologous bone marrow transplant—A bone marrow transplant that uses the patient's own bone marrow. Anemia—A condition in which the number of red blood cells is below normal Erythroblastic leukemia cells. (© Richard Green, Science Source/Photo Researchers, Inc. Reproduced by permission.) under a microscope to identify abnormal red cells— which are larger than healthy cells—and to count the number of mature cells and blasts present. Cancer red cell precursors predominate, myeloid blasts also are seen, and multinucleated red cell precursors are common. Bone marrow examinations are also performed, either by aspiration or biopsy to examine the cell types further. Treatment Treatment for acute erythroblastic leukemia depends on the features of the cancer cells present and on the extent of the disease, as well as on the age of the patient, his symptoms, and general health condition. This disease can have an indolent course and may only require observation in the early stages. The treatment strategy is based on chemotherapy and in some patients, bone marrow or cell transplantations are indicated as well. Chemotherapy is usually administered in combinations of two or more drugs. Post-remission therapy includes maintenance chemotherapy for most patients. Clinical staging, treatments, and prognosis Acute erythroblastic leukemia is a very aggressive form of leukemia and does not respond well to the types of therapy used for a related type of cancer known as acute myelocytic leukemia. However, recent advances in chemotherapy protocols and bone marrow transplantation techniques, either allogeneic or autologous, have been identified as a means to increase the cure rate. The patient's cancerous bone marrow is first purged using drugs and radiation therapy before being replaced by healthy bone marrow that is obtained from a suitable donor (allogeneic) or from the patient himself (autologous). In the case of an autologous transplant, the bone marrow is treated outside the 6 Blast cells—Immature cancer cells. Also called promelocytes. Bone marrow aspiration—Common technique used to obtain a bone marrow sample from a patient. A needle is inserted into a marrow-containing bone, such as the hip (iliac crest) or sternum (breast bone) and a small amount of liquid bone marrow is removed for examination. Bone marrow biopsy—Another common technique used to obtain a bone marrow sample from a patient. Like bone marrow aspiration, it is performed with a needle, but a larger one is used and a small piece of bone is removed as well as bone marrow. Chemotherapy—The treatment of disease by means of chemicals. In cancer, the chemicals selectively destroy cancerous tissue. When cancer remission occurs, a course of maintenance chemotherapy is often prescribed so as to prevent recurrence. Erythrocyte—Red blood cell. Leukemia—Cancer of the blood-forming tissues. Myeloid blast cell—Type of cancer cell originating in the bone marrow. Platelet—A type of blood cell responsible for blood coagulation and for the repair of damaged blood vessels. Proliferation—Rapid reproduction of tissue. Remission—Complete or partial disappearance of the symptoms of cancer following treatment. patient's body to remove the cancer cells before transplantation. Coping with cancer treatment Like all types of leukemias, patients with acute erythroblastic leukemia usually experience a number of G A L E E N C Y C L O P E D I A O F CA N C E R Clinical trials In 2001, no clinical trials for this leukemia were registered with the National Cancer Institute. Prevention Since this form of cancer is very rare and its causes are largely unknown, no specific preventive measures can be recommended. Special concerns Patients diagnosed with acute erythroblastic leukemia require special support in that they must deal with having a rare form of cancer about which there is very little specific information available. This creates additional anxiety and special care must be taken to explain to the patient that an uncommon cancer is not an untreatable one. See Also Bone marrow aspiration and biopsy; Chronic myelocytic leukemia; Myeloproliferative diseases Resources BOOKS Jandl, James H. Blood. Textbook of Hematology. Boston: Little, Brown, 1996. PERIODICALS Shichishima, T., "Minimally Differentiated Erythroleukemia: Recognition of Erythroid Precursors and Progenitors." Internal Medicine 39(October 2000): 843-46. Mazzella, F.M., et al. "The Acute Erythroleukemias." Clinical Laboratory Medicine 20 (March 2000): 119-37. Novik, Y., et al. "Familial Erythroleukemia: A Distinct Clinical and Genetic Type of Familial Leukemias." Leuk. Lymphoma 30 (July 1998): 395-401. ORGANIZATIONS National Cancer Institute, Public Inquiries Office, Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (301)435-2848. <http://www.nci.nih.gov>. G A L E E N C Y C L O P E D I A O F CA N C E R Acute leukemia specific complications and side effects resulting from treatment, as well as emotional concerns. They require supportive care to cope with these issues and to maintain their comfort and quality of life during treatment. As with every serious disease, psychological stress is increased and it is important for patients to be able to discuss their needs and concerns about tests, treatments, hospital stays, and financial consequences of the illness. Family, friends, doctors, nurses, and other members of the health care team are the best sources of support, as well as social workers, counselors, and members of the clergy. QU E S T I O N S TO A S K T H E D O C TO R • How can I obtain information on a rare cancer such as acute erythroblastic leukemia? • How are my chances of recovery affected by the fact that this cancer is so rare? National Cancer Information Center. 1-800-ACS-2345. The Leukemia and Lymphoma Society of America. 1-800-9554572. <http://www.leukemia-lymphoma.org/>. OTHER American Cancer Society's Consumer Guide to Cancer Drugs.Caregiving—A Step-by-Step Resource for Caring for the Person with Cancer at Home. Available from: American Cancer Society. (800) ACS-2345. <http:// www.cancer.org.>. Advanced Cancer: Living Day by Day.Chemotherapy and You: A Guide to Self-help During Treatment.Eating Hints for Cancer Patients.What You Need to Know About Leukemia. Available from: National Cancer Institute, National Institute of Health. (800) 4-CANCER. <http://www.nci.nih. gov>. Monique Laberge, Ph.D. Acute leukemia Definition A rapidly progressing cancer that starts in the bloodforming cells of the bone marrow. Leukemia results from an abnormal development of leukocytes (white blood cells) and their precursors. Leukemia cells look different than normal cells and do not function properly. Description There are four main types of leukemia, which can be further divided into subtypes. When classifying the type of leukemia, the first steps are to determine whether the cancer is lymphocytic or myelogenous (cancer can occur in either the lymphoid or myeloid white blood cells) and whether it is acute or chronic (rapidly or slowly progressing). In acute leukemia, the new or immature cells, called blasts, remain very immature and cannot perform their functions properly. The blasts rapidly increase in number 7 Acute lymphocytic leukemia and the disease progresses quickly. Major types of acute leukemia include acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML; also known as acute myelogenous leukemia). Kate Kretschmann Acute lymphocytic leukemia Definition Acute lymphocytic leukemia is a cancer of the white blood cells known as lymphocytes. Description Leukemia is a cancer of white blood cells. In acute leukemia, the cancerous cells are immature forms called blasts that cannot properly fight infection; patients become ill in rapid fashion. The cells that make up blood are produced in the bone marrow and the lymph system. The bone marrow is the spongy tissue found in the large bones of the body. The lymph system includes the spleen (an organ in the upper abdomen), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat). In addition, the lymph vessels (tiny tubes that branch like blood vessels into all parts of the body) and lymph nodes (peashaped organs that are found along the network of lymph vessels) are also part of the lymph system. The lymph is a milky fluid that contains cells. Clusters of lymph nodes are found in the neck, underarm, pelvis, abdomen, and chest. The main types of cells found in the blood are the red blood cells (RBCs), which carry oxygen and other materials to all tissues of the body; white blood cells (WBCs), which fight infection; and the platelets, which play a part in the clotting of the blood. The white blood cells can be further subdivided into three main types: granulocytes, monocytes, and lymphocytes. The granulocytes, as their name suggests, have particles (granules) inside them. These granules contain special proteins (enzymes) and several other substances that can break down chemicals and destroy microorganisms such as bacteria. Monocytes are the second type of white blood cell. They are also important in defending the body against pathogens. The lymphocytes form the third type of white blood cell. The two types of lymphocytes are Bcells, which make antibodies, and T-cells, which make other infection-fighting substances. Lymphocytic leukemia can arise in either B or T cells. 8 B-cell leukemia occurs more frequently than T-cell leukemia. It is the most common form of leukemia in children, but also occurs in adults. At diagnosis, leukemic cells can be found throughout the body, in the bloodstream, the lymph nodes, spleen, liver, occasionally in the central nervous system, and in T-cell ALL, the thymus gland. Cancerous lymphoblasts take over the bone marrow, reducing both the number and the effectiveness of all types of blood cells. The cancerous cells reduce the ability of healthy white cells to fight infection. Fewer red cells are produced, causing anemia, and fewer platelets increases the risk of bleeding and bruising. The presence of the cancerous white cells in the central nervous system can produce headaches, confusion and seizures. The type of treatment a person receives for ALL depends on the presence of risk factors for relapse. Children are at standard risk if they are between ages 1 and 9, have a total white cell count of less than 50,000 per microliter of blood, and have B-precursor cell leukemia. Children are at high risk if they are younger than 1 or older than 9, if their white blood cell count exceeds 50,000 per microliter, or if they have T-cell leukemia. Compared to children, adults are all at higher risk of relapse at the time of diagnosis, but younger adults (less than 25 years old) have a better prognosis. B-cell ALL constitutes about 80% of all cases. The cancerous cells are either early pre-B cells, the most immature, pre-B cells, also somewhat immature, or Bcells. These B-lineage cells contain a variety of proteins called antigens. The presence of one of these antigens, called CALLA for common ALL antigen, carries a somewhat more favorable prognosis. T-cell ALL has a less favorable prognosis than Bcell ALL. The presence of an antigen called CD2 indicates a more favorable prognosis. ALL is also classified by karyotype, which is the number and composition of a cell's chromosomes. Normal human cells contain 46 chromosomes. One chromosomal abnormality often seen in ALL is a translocation, in which a piece of one chromosome becomes attached to a different chromosome. Different translocations carry different prognoses. One translocation, labeled t(9;22) is also called the Philadelphia chromosome and is found in 5% of childhood ALL and 20% of adult ALL cases. The Philadelphia chromosome carries a somewhat less favorable prognosis. The number of chromosomes found in the leukemic cells, particularly in children, also impacts prognosis. The occurrence of more than 50 chromosomes in leukemic cells has a very favorable prognosis. Even the presence of one extra chromosome can be favorable. G A L E E N C Y C L O P E D I A O F CA N C E R Acute lymphocytic leukemia Children whose leukemic cells have fewer than 45 chromosomes are at highest risk of treatment failure. Demographics ALL is less common than AML in adults; about 1500 adults are diagnosed with ALL each year, compared to 10,000 diagnosed with AML. About 1000 adults die of ALL each year and the overall five-year survival rate for adults with ALL is 58%. About 1500 cases of ALL are diagnosed in children under 18 each year in the United States. ALL is by far the more common form of leukemia in children. The death rate for children with ALL has dropped nearly 60% in the last 30 years. The overall five-year survival rate for children with ALL is now 80%. Still, leukemia causes more deaths in children under 15, about 550 per year, than any other disease. In the United States, ALL is highest among Caucasians and lowest among Asian-Americans. The incidence of ALL is about 50% higher for men than for women. Death rates in leukemia patients are highest in African-Americans and Caucasians and lowest in Asians. In children, the highest leukemia rates in the US occur among those of Filipino descent; next highest are white Hispanics, then non-Hispanic whites, and the lowest incidence in children is in African-Americans. Survival is higher for Caucasians than African-Americans. The survival rate for girls is slightly higher, in part due to the risk of relapse occurring in the testicles and in part because boys appear to have a slightly higher risk of bone marrow relapse. Causes and symptoms Causes While specific causes for ALL are not known, there are some known risk factors, including ionizing radiation. Exposure to certain chemicals, particularly benzene (used in the manufacture of plastics, rubber, and some medicines), has also been associated with an increased risk of developing ALL. ALL incidence in adults increases with age. The causes of ALL in children are also unknown. Certain inherited genetic abnormalities, such as Down syndrome, increase the risk. Some studies have shown prenatal exposure to ionizing radiation increases a child's risk of ALL. Some contaminants of tap water, such as trihalomethanes, chloroform, zinc, cadmium, and arsenic are associated with an increased risk. A number of reports suggested an increased risk of ALL among children who lived in proximity to high voltage power lines, G A L E E N C Y C L O P E D I A O F CA N C E R False-color scanning electron micrograph (SEM) of white blood cells from a patient with acute lymphocytic leukemia. In this disease, certain types of white blood cells are overproduced, and these abnormal cells suppress the normal function of white and red cells, increasing the susceptibility to infections. (© Professor Aaron Polliack, Science Source/Photo Researchers, Inc. Reproduced by permission.) but several later analyses suggested that was not true. Studies continue in efforts to disprove or confirm this possible connection. ALL is more common in children who are not firstborn and among those whose mothers took antibiotics during their pregnancies. Breastfeeding has been found to be protective. Symptoms ADULTS. ALL in adults can cause any or all of the following symptoms: • fevers, chills, sweats • weakness, fatigue, shortness of breath • frequent infections • depressed appetite, weight loss • enlarged lymph nodes • easy bleeding or bruising • rash of small, flat red spots (petechiae) • bone and joint pain Symptoms of central nervous system involvement include: • headache • nausea and vomiting • confusion • seizures CHILDREN. Symptoms in children are similar, but young children may be unable to communicate them. They include: • fevers 9 Acute lymphocytic leukemia • frequent infections • fatigue, irritability, decreased activity levels • easy bruising or bleeding • bone or joint pain • a limp • swollen belly • enlarged lymph nodes T-cell ALL can invade the thymus gland in the upper chest, which can cause compression of the windpipe, cough or shortness of breath, and superior vena cava syndrome (compression of a large vein that causes swelling of the head, neck, and arms). Central nervous system involvement in children produces: • headache • nausea and vomiting • blurred vision • decline in school performance • seizures Spread to the testicles can cause painless swelling in them. Diagnosis There are no screening tests for leukemia. The patient's history and physical examination raise the physician's suspicions, triggering orders for appropriate tests. Pallor, swollen lymph nodes, bleeding, bruising, pinpoint red rashes, and in children, a swollen abdomen, will suggest the diagnosis. Testing is similar for adults and children. The first test is a complete blood count (CBC), examining red cells, platelets and white cells. In early leukemia, the total white blood cell count might be normal, but there will usually be circulating lymphoblasts, which is always abnormal. The red cell and platelet counts may be low. The abnormal CBC results trigger a referral to a hematologist/oncologist who will perform a bone marrow aspiration and biopsy, in which a small sample of marrow is removed with a hollow needle inserted in the hipbone. Although topical anesthetic will numb the skin and bone, most patients experience brief pain during this procedure. The sample will be examined microscopically for evidence of lymphoblasts. The marrow will be further studied to determine whether the lymphoblasts are of Tcell or B-cell origin and the cells tested for chromosomal abnormalities. A pathologist can examine the marrow and 10 make the diagnosis immediately. The chromosome studies require several days to complete. The bone marrow aspirate will be repeated occasionally during treatment to confirm remission and to look for possible relapse. A lumbar puncture, or spinal tap, will be performed to rule out spread of ALL to the central nervous system. A thin needle is inserted between two vertebrae in the lower back, and spinal fluid removed. This fluid is examined microscopically for the presence of lymphoblasts. Topical anesthetics eliminate most of the discomfort of a spinal tap, although many patients experience headaches afterwards. Remaining flat for 30 minutes after a spinal tap decreases the likelihood of headache. A chest x ray will show enlargement of internal lymph nodes or the thymus gland. No preparation is necessary for most of the testing done to diagnose ALL. Younger children will often receive mild sedatives before procedures like spinal taps and bone marrow studies. Topical anesthetic cream can be applied an hour in advance of either a bone marrow test or a spinal tap. When treatment is complete, tests for minimal residual disease can be performed. These new tests detect the presence of lingering leukemic cells that would have been missed by standard testing. The presence of a certain amount of residual disease probably has an impact on prognosis and the likelihood of relapse. Treatment team The treatment team consists of a hematologist/ oncologist who directs care, oncology nurses familiar with administering chemotherapy, and often social workers, who can address both insurance issues and psychological support. The patient's regular physician should be kept informed of all cancer-related care. Because treatment is so prolonged, most patients have long-term intravenous catheters placed by a surgeon. In many hospitals, a Child Life specialist will participate in the care of children with ALL. They ensure that children with cancer are seen, first and foremost, as children, organizing play times, providing distraction during scary procedures and giving parents some much-needed respite. Clinical staging, treatments, and prognosis ALL does not have a formal staging system, but treatment is different in different phases of the disease. These phases are often divided into untreated ALL, ALL in remission, and recurrent ALL. Conventional treatment for ALL consists of chemotherapy for disease in the bone G A L E E N C Y C L O P E D I A O F CA N C E R ADULTS. The first phase of treatment is remission induction. The chemotherapeutic drugs typically include prednisone, vincristine, cytarabine, cyclophosphamide and asparaginase. Most are given intravenously and a few are given orally. Depending on the disease, these drugs can achieve a complete remission in 60% to 90% of adults. The relapse rate is higher in adults than in children. A 50% 3-year survival has been noted in some research series, and very aggressive treatment with multiple drugs has produced up to a 70% survival rate. Adverse effects of these drugs include: • bone marrow suppression • anemia, pallor, fatigue, shortness of breath, and angina in older patients • bleeding, bruising • increased risk of infection • hair loss (alopecia) • mouth sores • nausea and vomiting • menopausal symptoms • lower sperm counts • tumor lysis syndrome, in which the dead cancer cells can harm healthy organs Treatment that is directed at preventing central nervous system spread is called prophylactic. Because of the blood brain barrier, a physical and chemical barrier that prevents toxins from reaching the brain and spinal cord, chemotherapeutic drugs do not easily reach the central nervous system. Thus, chemotherapeutic drugs are administered directly into spinal fluid, which circulates around the brain and spinal cord. This is called intrathecal chemotherapy. The drugs are given by spinal tap or through an Ommaya reservoir, which is surgically inserted under the scalp. This reservoir empties into the spinal fluid around the brain. Some patients receive prophylactic radiation therapy to the brain, in addition to or instead of intrathecal chemotherapy. CHILDREN. The treatment of ALL in children represents one of the great success stories of modern oncology. In contrast to adults, most children with cancer enter into research protocols, strict treatment regimens with careful follow-up that are built on the most successful aspects of earlier treatments. Childhood ALL now has an 80% long-term survival rate, due in large part to the extensive and widely disseminated research on the dis- G A L E E N C Y C L O P E D I A O F CA N C E R ease. Within the United States, research on ALL was conducted for many years under the auspices of either the Children's Cancer Group or the Pediatric Oncology Group. In 1998, recognizing the benefits of cooperation and collaboration, these two groups joined forces with the National Wilms' Tumor Study Group and the Intergroup Rhabdomyosarcoma Study Group to form the Children's Oncology Group. Remission induction chemotherapy for children includes vincristine, a steroid, and asparaginase. Children at higher risk of relapse are often given daunomycin as well. The adverse effects of these drugs include bone marrow suppression, risk of infection, nausea, vomiting, hair loss, and mouth sores. Although these drugs can reduce sperm counts, most survivors of childhood ALL grow up to have normal fertility. The drugs can be administered intravenously or as oral preparations. Oral prednisone has a particularly unpleasant taste that is hard to disguise and parents must be vigilant to ensure that their children are taking their proper doses. Like adults, children also receive prophylaxis against central nervous system spread. They receive multiple doses of intrathecal chemotherapy, with the drugs delivered directly to the spinal fluid through a lumbar puncture or spinal tap. Cranial radiation as central nervous system prophylaxis for children is infrequently used. Though once standard, brain radiation produced a high incidence of cognitive and learning disabilities, especially among those younger than five years old. Cranial radiation is reserved for those children felt to be at high risk of central nervous system disease, including those older than ten at the time of diagnosis, those with initial white blood cell counts of more than 50,000 per microliter, and those with T-cell leukemia. Some high-risk children who enter remission rapidly with induction chemotherapy receive intrathecal chemotherapy alone, without radiation therapy. Alternative and complementary therapies ADULTS. Individuals with leukemia often employ alternative or complementary therapies. Some of these provide pain relief and improve psychological well being. No controlled studies have yet shown that alternative treatments offer cures for ALL, although some may hold promise of benefit. Patients with ALL sometimes use acupuncture, which offers relief from generalized pain, nausea, and vomiting. Other methods that may help with the physical and often emotional side effects of treatment include hypnosis, guided imagery, and yoga. Nutritional supplements and herbs are sometimes utilized by persons with leukemia. Coenzyme Q10 is an 11 Acute lymphocytic leukemia marrow and treatment aimed at preventing central nervous system disease. Acute lymphocytic leukemia antioxidant, a substance that protects cells from toxic byproducts of metabolism. Early studies suggest, although it is not proven, that coenzyme Q10 can improve immune function and counteract some of the harmful effects of chemotherapy and radiation on healthy cells. Adverse effects of coenzyme Q10 include headache, rash, heartburn and diarrhea. Another supplement with potential benefit is polysaccharide K (PSK). A few studies have shown PSK to have some benefit in improving immunity. Supplements that have not been proven to be of value or are potentially dangerous to those with leukemia include camphor, sometimes called 714-X. Green tea has received much press for its reported abilities to enhance the immune system and fight cancer, but studies have had conflicting results. Some show that green tea has preventive benefits and others show no effect. A few animal studies suggest that growth of tumors might be slowed by green tea, but this has not been shown in humans yet. Hoxsey is another supplement touted as a cancer treatment, but no studies have confirmed any benefit. Some of its ingredients have serious adverse effects. Vitamin megadoses have long been advocated as beneficial in cancer, but no conclusive studies show benefit, and they have significant potential for adverse effects, such as diarrhea, kidney stones, iron overload, nerve damage and liver disease. Laetrile, or amygdalin, was once touted as a cure for cancer and leukemia. No human or animal studies conducted in the decades since have shown any benefit other than relief of some pain. Laetrile can, however, cause cyanide poisoning. CHILDREN. Complementary and alternative treatments are recommended less frequently for children. Real caution must be used in administering herbal remedies to children, whose metabolisms are very different from those of adults. For example, jin bu hua, a traditional Chinese medicine, can cause heart or breathing problems. Life root and comfrey can both cause fatal liver damage in children. While many children are too young for formal guided imagery, they can be distracted from the fears and pain associated with some treatments by toys and videotapes. Reading favorite books during scary procedures can relieve some of their fears. ALL in remission ADULTS. Remission is achieved in many people within days of beginning treatment. Treatment does not end at that point, but rather enters into the next phases, called consolidation and maintenance. Several different 12 approaches can be used in these. Some patients receive long-term chemotherapy with drugs that might include cytarabine, cyclophosphamide, methotrexate, 6-mercaptopurine, vincristine, prednisone, or doxorubicin. Other patients undergo high-dose chemotherapy or combination chemotherapy and radiation therapy to ablate or wipe out their own bone marrow, and then have bone marrow or stem cell transplants. Adverse effects of bone marrow transplant include significant risk of serious infection and graft versus host disease (GVHD), in which the transplanted cells fail to "recognize" the host's cells as self and attack the host cells. Medications to decrease this risk include those that suppress the immune system and steroids. Central nervous system prophylaxis, as either intrathecal chemotherapy or radiation therapy or both, typically continues through at least a portion of the postremission therapy. Adults who receive intensive chemotherapy have a 40% likelihood of long-term survival. CHILDREN. In children, remission induction therapy is followed by a phase termed consolidation or intensification, and then by a phase termed maintenance. During intensification, children receive intermediate or highdose methotrexate, plus some of the same drugs that are used in induction, new drugs that do not cross-react with those used in induction, high-dose asparaginase, or some combination of these. The maintenance phase of treatment for children with ALL continues for 18 to 30 months. Daily oral mercaptopurine and weekly oral or injected methotrexate are given on an outpatient basis, with frequent blood tests and examinations. Some protocols add pulses of vincristine and prednisone during the maintenance phase. Recurrent ALL ADULTS. Adults who relapse after initial remission and maintenance therapy often undergo reinduction chemotherapy and are then referred for bone marrow or stem cell transplant. Some receive transplants of umbilical cord blood. Such transplants carry the risk of graft versus host disease, but also carry the possibility of graft versus leukemia, in which the transplanted cells attack the residual leukemic cells. Unlike graft-versus-host disease, graft versus leukemia is useful. New treatments for relapsed ALL include immunotherapies or biological response modifiers. Some reduce adverse effects of treatment and others are used to fight the leukemia. Some of these include cytokines, substances that stimulate the production of blood cells after treatment has suppressed the bone marrow, and colonyG A L E E N C Y C L O P E D I A O F CA N C E R CHILDREN. The treatment and prognosis of children who relapse depends on the timing of that relapse. Relapse that occurs within six months is often treated with bone marrow transplantation. Early relapse carries the least favorable prognosis, with only 10% to 20% chance of long-term survival. Relapse that occurs more than a year after initial treatment is finished can be treated with another full round of chemotherapy, and bone marrow transplant reserved for those children who relapse a second time. Those with such late relapses have a 30% to 40% chance of long-term survival. Recurrent disease may occur in a sanctuary site, or a part of the body difficult to penetrate with chemotherapeutic drugs. The central nervous system is the most common site of such recurrences. Children who have an isolated central nervous system relapse during the first 18 months of treatment have a 45% likelihood of longterm survival. Children with central nervous system relapse after the first 18 months of treatment have up to an 80% chance of long-term survival. Treatment for relapse in the central nervous system includes intrathecal chemotherapy, and for most children, the use of radiation therapy to the brain and spinal cord. The testicles are the second most common site of relapse. Early testicular relapse (within the first 18 months of treatment) carries a 40% chance of long-term survival, and late testicular relapse carries an 85% chance of long-term survival. Another sanctuary site is the eye, but isolated relapse here is unusual. Coping with cancer treatment The treatment of ALL can be particularly draining, not only due to adverse effects but due to its prolonged time course. Although much of the treatment can be given on an outpatient basis, many protocols utilize lengthy intravenous infusions of chemotherapy and require hospitalization. ADULTS. To prevent nausea and vomiting, adults can take oral anti-nausea medication an hour or so before scheduled treatments, including intrathecal treatments. To avoid headache, they should remain flat for at least 30 to 60 minutes after intrathecal chemotherapy. Nurses can give instructions in mouth care if mouth sores occur and skin care if rashes occur after radiation treatment. Books, music, and television can provide distraction and reduce anxiety during chemotherapy infusions. G A L E E N C Y C L O P E D I A O F CA N C E R KEY TERMS Antiangiogenic drugs—Drugs that block the formation of new blood vessels. Blasts—Immature blood cells. CBC—Complete blood count, a blood test that measures red cells, white cells and platelets. Graft versus host disease—After bone marrow transplant, the newly transplanted white blood cells can attack the patient's own tissues. Intrathecal chemotherapy—Chemotherapeutic drugs instilled directly into the spinal fluid, either by spinal tap or through a special reservoir. Karyotype—The number and type of chromosomes found within cells. Lymphoblasts—The cancerous cells of ALL, immature forms of lymphocytes, white blood cells that fight infection. Ommaya reservoir—A special device surgically placed under the scalp with a direct connection to spinal fluid. Medications to treat central nervous system disease are injected into the reservoir. Petechiae—Pinpoint red spots seen on the skin with low platelet counts. Philadelphia chromosome—An abnormal chromosome found in 20% of adults and 5% of children with ALL, the presence of which indicates a somewhat worse prognosis. Sanctuary sites—Areas within the body which are relatively impermeable to medications such as chemotherapy but which can harbor cancerous cells. Some of these sites are the central nervous system, the testicles, and the eyes. Thymus—A gland within the chest involved in the maturation of immune cells that can be invaded by T lymphocytes in T-cell ALL. Patients scheduled for inpatient stays can bring their own pillows, pajamas and even food, with their doctor's approval. Temporary issuance of handicapped parking stickers are often helpful. CHILDREN. The presence of parents during treatment is critical. While some hospitals exclude parents during treatments, others invite them to be present. Blood can be drawn and intravenous catheters placed while children sit in their parents' laps. If at all possible, a parent should spend the night during any hospitalizations. 13 Acute lymphocytic leukemia stimulating factors, which have the same effect. Other immunotherapies, such as monoclonal antibodies and interferon, have not yet been shown effective against ALL, but are still under study. Acute lymphocytic leukemia QU E S T I O N S TO A S K T H E D O C TO R • What type of leukemia do I or does my child have? • What characteristics of my or my child's illness are favorable? Which are unfavorable? • What course of therapy do you recommend? • What medications will you use and what side effects are anticipated? • Will I or my child need to be hospitalized for those treatments? • Should I or my child be enrolled in a clinical trial? • Can I continue to work or can my child go to school? • Can I stay with my child for procedures? For hospitalizations? • How and what should we tell our child about this illness? • What should we tell our other children? Like adults, children can take anti-nausea drugs an hour or so before scheduled treatments. Children, and some adults, can apply topical anesthetic creams to sites of bone marrow aspirates or spinal taps. Favorite stuffed animals or blankets can be present for most procedures. Play and fun are as important to children with cancer as to healthy children. Items such as board games, modeling clay, video games, dolls, and toy cars can be enjoyed even with intravenous lines in place. Play dates with friends should be encouraged, with proper screening to limit exposure to contagious illnesses. School districts are required to accommodate the special needs of children. Children with ALL might require shorter school days or the provision of a tutor at home. Children who develop learning disabilities due to treatment might require the intervention of a special education team. Clinical trials There are numerous clinical trials looking at novel strategies for the treatment of ALL in adults and children. Most oncologists consider bone marrow transplants to be state-of-the-art in specific circumstances, and some insurance companies agree. Many still require extensive reviews before approving coverage for transplant. 14 A variety of biological agents are currently under study. These include antibodies that react specifically against leukemic cells, causing their death, and chemicals that interfere with the leukemic cells' normal DNA function or their ability to make proteins. Researchers are developing second and third generation versions of established chemotherapeutic drugs, isolating the molecular components of those drugs that seem to be most useful in ALL and amplifying them. Some of these drugs include 9-aminocamptothecin, aminopterin, annamycin, Ara-G, codrycepin, decitabine, and trimetrexate. Quinine shows promise in reducing the incidence of drug resistance that is sometimes seen in leukemic cells. Locating and enrolling in clinical trials has been made easier by listings on the Internet. A general search under "clinical trials and leukemia" will yield several listings. University-affiliated hospitals and oncologists participate in many trials and can refer patients to other sites if necessary. Prevention There are few preventive measures to take against ALL. Those who work with chemicals should be cautious, particularly around benzene. Pregnant women should avoid exposure to ionizing radiation to reduce the risk to their unborn children. Special concerns Parents of children with ALL have specific concerns regarding the long-term consequences of treatment for ALL, such as learning disabilities. Organizations devoted to childhood cancer, hospital social workers, pediatric oncologists and other parents can be important resources when advocating for the educational needs of the child with ALL. When cranial radiation must be used, children have a risk of developing secondary cancers in the central nervous system years later. Some children are left infertile by the treatment. Chicken pox can be lethal in children with ALL. The introduction of the chicken pox vaccine has reduced this risk, but parents must still be vigilant. Resources BOOKS Lackritz, Barb. Adult Leukemia: A Comprehensive Guide for Patients and Families. Sebastopol, CA: O'Reilly & Associates, 2001. Keene, Nancy, and Linda Lamb.Childhood Leukemia: A Guide for Families, Friends & Caregivers. Sebastopol, CA: O'Reilly & Associates, 1999. G A L E E N C Y C L O P E D I A O F CA N C E R Veritas A service of Harvard Medical School, listing clinical trials throughout the US. 9 July 2001 <http://www.veritas medicine.com/leukemia> International clinical trials listings. 9 July 2001 <http://www. graylab.ac.uk/cancerweb/trials.html> Why, Charlie Brown, Why? Videotape. Topper Books, 1990. Marianne Vahey, M.D. PERIODICALS Gaynon, P.S., et al. "Children's Cancer Group Trials in Childhood Acute Lymphoblastic Leukemia: 1983–1995." Leukemia 14, no. 5 (December 2000): 2223–33. Greaves, M.F. "Aetiology of Acute Leukaemia." The Lancet 349, no. 9048 (February 1997): 344–9. Hasle, H., et al. "Risks of Leukaemia and Solid Tumours in Individuals with Down Syndrome." The Lancet 355, no. 9199 (January 2000): 165–9. Pui, C.H. "Acute Lymphoblastic Leukemia in Children." Current Opinions in Oncology 12, no. 1 (January 2000): 3–12. Weisdorf, D.J. "Bone Marrow Transplantation for Acute Lymphoblastic Leukemia (ALL)."Leukemia 11, Supp. 4 (May 1997): 420–2. ORGANIZATIONS The Leukemia and Lymphoma Society of America (formerly The Leukemia Society of America). 1311 Mamaroneck Ave., White Plains, NY 10605. (914) 949-5213. <http:// www.leukemia-lymphoma.org>. American Cancer Society. 1599 Clifton Rd., Atlanta, GA, 30329. (800) ACS-2345. <http://www.cancer.org>. The National Cancer Institute. Cancer Information Service. Building 31, Room 10A31, 31 Center Dr., MSC 2580, Bethesda, MD 20892-2580. (301) 435-3848. <http:// www.nci.nih.gov/> Cancer Care, Inc. 1180 Avenue of the Americas, New York, NY 10036. (212) 302-2400 or (800) 813-4673. <http://www. cancercare.org> National Marrow Donor Program. Suite 500, 3001 Broadway St. NE, Minneapolis, MN 55413-1753. (800) MARROW2. <http://www.marrow.org/> Candlelighters Childhood Cancer Foundation. 7910 Woodmont Ave., Suite 460, Bethesda, MD 20814. (800) 366-CCCF. <http://www.candlelighters.org> National Childhood Cancer Foundation. 440 E. Huntington Dr., P.O. Box 60012, Arcadia, CA 91066-6012. (626) 4471674. <http://www.nccf.org> OTHER PDQ (Physician Data Query). (800) 4-CANCER. 9 July 2001 <http://cancernet.nci.nih.gov> GrannyBarb and Art's Leukemia Links. 9 July 2001 <http:// www.acor.org/diseases/hematol