Moshe Talpaz - Medical management of chronic myelogenous leukemia

Cover

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MedicalManagementofChronicMyelogenousLeukemia

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BASIC AND CLINICAL ONCOLOGY

Editor

Bruce D. Cheson, M.D.

National Cancer Institute

National Institutes of HealthBethesda, Maryland

1. Chronic Lymphocytic Leukemia: Scientific Advances and Clinical Developments, edited by Bruce D. Cheson

2. Therapeutic Applications of Interleukin-2, edited by Michael B. Atkinsand James W. Mier

3. Cancer of the Prostate, edited by Sakti Das and E. David Crawford

4. Retinoids in Oncology, edited by Waun Ki Hong and Reuben Lotan

5. Filgrastim (r-metHuG-CSF) in Clinical Practice, edited by GeorgeMorstyn and T. Michael Dexter

6. Cancer Prevention and Control, edited by Peter Greenwald, Barnett S.Kramer, and Douglas L. Weed

7. Handbook of Supportive Care in Cancer, edited by Jean Klastersky,Stephen C. Schimpff, and Hans-Jrg Senn

8. Paclitaxel in Cancer Treatment, edited by William P. McGuire and EricK. Rowinsky

9. Principles of Antineoplastic Drug Development and Pharmacology, edited by Richard L. Schilsky, Grard A. Milano, and Mark J. Ratain

10. Gene Therapy in Cancer, edited by Malcolm K. Brenner and Robert C.Moen

11. Expert Consultations in Gynecological Cancers, edited by Maurie Markman and Jerome L. Belinson

12. Nucleoside Analogs in Cancer Therapy, edited by Bruce D. Cheson,Michael J. Keating, and William Plunkett

13. Drug Resistance in Oncology, edited by Samuel D. Bernal

14. Medical Management of Hematological Malignant Diseases, edited byEmil J Freireich and Hagop M. Kantarjian

15. Monoclonal Antibody-Based Therapy of Cancer, edited by Michael L.Grossbard

16. Medical Management of Chronic Myelogenous Leukemia, edited byMoshe Talpaz and Hagop M. Kantarjian

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ADDITIONAL VOLUMES IN PREPARATION

Cancer Screening: Theory and Practice, edited by Barnett S. Kramer,John K. Gohagan, and Philip C. Prorok
Expert Consultations in Breast Cancer: Critical Pathways and ClinicalDecision Making, edited by William N. Hait, David A. August, andBruce Haffty

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edited by

Moshe Talpaz

Hagop M. Kantarjian

University of Texas M.D. Anderson Cancer Center

Houston, Texas

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Library of Congress Cataloging-in-Publication Data

Medical management of chronic myelogenous leukemia / edited by Moshe Talpaz,
Hagop M. Kantarjian.

p. cm. (Basic and clinical oncology; 16)

Includes bibliographical references and index.

ISBN 0-8247-9901-1 (alk. paper).

1. Myelocytic leukemiatreatment. I. Talpaz, Moshe. II. Kantarjian, Hagop. III.

Series.

[DNLM: 1. Leukemia, Myeloid, Chronictherapy. W1BA813W v. 16 1998]

RC643.M434 1998

616.99419dc21

DNLM/DLC

This book is printed on acid-free paper.

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PRINTED IN THE UNITED STATES OF AMERICA

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Historically, the therapeutic objective in CML was the normalization of bloodcounts with the basic understanding that this action will have little impact onthe predictable fatal outcome of the disease. With the development of allogeneicbone marrow transplant came the notion that the disease is a potential target forcurative therapy. This effect was, however, confined to only a fraction of thepatients. Interferon alpha (IFN-) was initially given to CML patients in theearly 1980s and gradually became the foundation for nontransplant treatment ofthe disease. This is based on its ability to obtain survival prolongation in mostof the patients and a complete sustained remission in a fraction of the patients.Our current therapeutic issues include the formation of therapeutic algorithmsthat will enable adequate incorporation of the two aforementioned therapeuticmodalities and improvement of the existing therapies by developing combination therapies (IFN- combined with Ara-C) or new allo-transplantation strategies, such as matched unrelated donor (MUD) transplantation.

This book summarizes new developments in the therapy of CML. Becausethe major therapies (IFN and bone marrow transplantation) are discussed inmore than one chapter, the reader will be subjected to different points of viewas to the significance of each therapy and its priority in the global therapeuticschema of CML.

CML has also been the subject of an intense effort to decipher its underlying molecular defect. The knowledge accumulated has provided the basis forthe current approaches in investigational therapies. These rational approachestoward the treatment of CML, which include antisense oligonucleotides to bcr-abl and C-Myb transcripts, bcr-abl kinase inhibitors, and bcr-abl-based immunotherapy, are discussed in this book and provide the link to future therapies ofthis disease.

In addition to the extensive coverage of therapies for CML, this bookalso provides information on the rapidly evolving disease-monitoring moleculartechniques such as fluorescent in situ hybridization (FISH), polymerase chain

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reaction (PCR) amplification of the bcr-abl gene product, and the bcr Southernblot assay. The value of these methods for disease monitoring and their possibleadvantages over the commonly used cytogenetic assays are discussed as well.