Biologic Therapy of Leukemia Contemporary Hematology

BIOLOGIC THERAPY OF LEUKEMIA CONTEMPORARY HEMATOLOGY Gary 1. Schiller, MD, SERIES EDITOR Biologic Therapy of Leukemia, edited by MATT KAIAYCIO, 2003 Chronic Lymphocytic Leukemia: Molecular Genetics, Biology, Diagnosis, and Management, by GUY B. FAGUET, 2003 Modern Hematology: Biology and Clinical Management, by REINHOW MUNKER, ERHARD HILLER, AND RONALD PAQUETTE, 2000 Red Cell Transfusion: A Practical Guide, edited by MARION E. REID AND SANDRA J. NANCE, 1998 BIOLOGIC THERAPY OFLEUKEMIA Edited by MATT KALAYCIO, MD The Cleveland Clinic Foundation, Cleveland, OH ~ HUMANA PRESS ~ lrOTOVVA, ~EVVJERSEY © 2003 Humana Press Inc. Softcover reprint of the hardcover I st edition 2003 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 humanapress.com For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel: 973-256-1699; Fax: 973-256-8341; E-mail: [email protected]; website at humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or other wise without written permission from the Publisher. All articles, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher. Due diligence has been taken by the publishers, editors, and authors of this book to ensure the accuracy of the information published and to describe generally accepted practices. The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate in accord with the standards accepted at the time of publication. Notwithstanding, as new research, changes in government regulations, and knowledge from clinical experience relating to drug therapy and drug reactions constantly occurs, the reader is advised to check the product information provided by the manufacturer of each drug for any change in dosages or for additional warnings and contraindications. This is of utmost importance when the recommended drug herein is a new or infrequently used drug. It is the responsibility of the health care provider to ascertain the Food and Drug Administration status of each drug or device used in their clinical practice. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences from the application of the information presented in this book and make no warranty, express or implied, with respect to the contents in this publication. This publication is printed on acid-free paper. @ ANSI Z39.48-1984 (American National Standards Institute) Permanence of Paper for Printed Library Materials. Production Editor: Robin B. Weisberg. Cover Illustration: From Fig. 5 in Chapter 4, "Drug Immunoconjugate Therapy of Acute Myeloid Leu kemia" by Arthur E, Frankel, Bayard L. Powell, Eli Estey, and Martin S. Tallman. Cover design by Patricia F. Cleary. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $20.00 per copy is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Reporting Service is: [1-58829-071-9/03 $20.00]. Library of Congress Cataloging-in-Publication Data Biologic therapy of leukemia 1 edited by Matt Kalaycio. p.; cm.-- Includes bibliographical references and index. ISBN 978-1-4684-9777-9 ISBN 978-1-59259-383-5 (eBook) DOI 10.1007/978-1-59259-383-5 1. Leukemia-Immunotherapy. 2. Leukemia--Gene therapy. 3. Cytokines-Therapeutic use. 4. Biological products-Therapeutic use. I. Kalaycio, Matt. II. Series. [DNLM: 1. Leukemia,therapy. 2. Biological Therapy. 3. Cytokines-therapeutic use. 4. Gene Therapy. 5. Immunotherapy. 6. Oligonucleotides, Antisense-therapeutic use. WH 250 B615 2003] RC643.B457 2003 616.99'41906---dc21 2002192220 To Linda, Mollie, Jason, and Rachel PREFACE In the latter part of the 20th century, hematologists and medical oncologists were trained to treat leukemia with systemic therapy that was cytotoxic to both normal and malignant cells. Some of these therapies, such as methotrexate and L-asparaginase, were developed within the context of known biologic patho physiology, but most were developed in relative ignorance of biologic mecha nisms and cannot therefore be considered "biologic." The usual goal of treatment was to eliminate rapidly dividing, or malignant, cells with DNA-damaging agents that spared normal tissue only in a relative sense. The paradigm of systemic, non specific therapy dominated oncologic thought at the time: Leukemia is by very definition a wide-spread systemic disease at the time of diagnosis. For this reason systemic therapy which reaches simultaneously every cell in the body is the most logical form oftreatment and is probably the only type which offers, theoretically, the possibility of complete cure. (1) To an extent, the systemic, nonspecific treatment approach was successful and certainly resulted in cures when before none were possible. However, this approach failed to cure the majority of patients with leukemia and is usually associated with significant toxicity. No other way was known, and for a time, no other way seemed possible. The frequent failure of nonspecific treatments, remarkable advances in molecular biology, and well-timed serendipity, led to new approaches that are revolutionizing the management of leukemia as we enter the 21st century. In contrast to the treatments of the past, the new approaches can collectively be classified as truly "biologic" therapies because they take advantage of the known biology of leukemia. Thus, treatment can often be directed at the leukemia, sparing normal tissues and causing less tissue damage. These new targeted treat ments represent the beginning of a new age in leukemia therapeutics. As exciting as these are, clinicians often find it difficult to access appropriate medical information on these new treatments when faced with a patient who may benefit from them. The advances are coming so often, and so quickly, that treat ments are sometimes approved for use before the information that supports their claimed efficacy can be published in peer-reviewed literature. Large textbooks attempting to publish accurate and current information on leukemia are doomed to obsolescence before reaching print. These practical concerns prompted the publication of this book. Biologic Therapy of Leukemia is devoted to these new biologic therapies and provides a vii viii Preface rapidly accessible, authoritative source of practical information for clinicians attempting to use these treatments for their patients. Some of the treatments described in this text, such as interferon and all-trans retinoic acid, have been available for some time and are well-described in the medical literature. However, that information is difficult to access when contrast ing their efficacy with newer treatments, such as imatinib mesylate and arsenic trioxide, which are also described in this text. Other treatments, such as P-glyco protein inhibitors and interleukins, have been dancing on the edges of clinical practice and may yet find their place based on emerging data. The graft vs leu kemia effect has been better defined and promises to completely alter the way allogeneic stem cell transplant is employed in the future. Finally, therapeutic approaches that reverse failure of apoptosis, alter genetic codes, and modulate immunologic mechanism are no longer mere theory, but are now being tested in the clinic and warrant close attention by the oncologic community. The authors and I hope that clinicians treating patients will find Biologic Therapy ofLeukemia helpful. We all share the goal of eradicating leukemia and I believe the information contained in these pages moves us closer to that goal. I thank the contributors for their expertise and willingness to share it. I stand in awe of their knowledge and dedication. Matt Kalaycio, MD REFERENCE 1. Burchenal, J.H. Treatment of the leukemias. Semin HematoI1966;3: 122. CONTENTS Preface ........................................................................................................... vii Contributors .................................................................................................... xi PART I: IMMUNOTHERAPY 1 Human Leukemia-Derived Dendritic Cells as Tools for Therapy .......................................................................................... 3 David Claxton 2 The Graft vs Leukemia Effect.. ............................................................. 13 Brian J. Bolwell 3 Unconjugated Monoclonal Antibodies ................................................. 29 Matt Kalaycio 4 Drug Immunoconjugate Therapy of Acute Myeloid Leukemia ........................................................................................... 43 Arthur E. Frankel, Bayard L. Powell, Eli Estey, and Martin S. Tallman 5 Radiolabeled Monoclonal Antibodies .................................................. 59 John M. Burke and Joseph G. Jurcic PART II: CYTOKINES 6 Interferons .............................................................................................

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