LEUKEMIA: ADVANCES IN RESEARCH AND TREATMENT
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1 LEUKEMIA: ADVANCES IN RESEARCH AND TREATMENT
2 CANCER TREATMENT and RESEARCH Livingston R.B. (ed): Lung Cancer ISBN Humphrey G.B., Dehner L.P., Grindey G.B., Acton R.T. (eds): Pediatric Oncology 1. ISBN DeCosse 1.1., Sherlock P. (eds): Gastrointestinal Cancer ISBN Bennett 1.M. (ed): Lymphomas 1, including Hodgkin's Disease ISBN Bloomfield e.d. (ed): Adult Leukemias ISBN Paulson D.F. (ed): Genitourinary Cancer ISBN Muggia F.M. (ed): Cancer Chemotherapy ISBN Humphrey G.B., Grindey G.B. (eds): Pancreatic Tumors in Children ISBN Costanzi 1.1. (ed): Malignant Melanoma ISBN Griffiths e.t., Fuller A.F. (eds): Gynecologic Oncology ISBN Greco A.F. (ed): Biology and Management of Lung Cancer ISBN Walker M.D. (ed): Oncology of the Nervous System ISBN Higby D.l. (ed): Supportive Care in Cancer Therapy ISBN Herberman R.B. (ed): Basic and Clinical Tumor Immunology ISBN Baker L.H. (ed): Soft Tissue Sarcomas ISBN Bennett 1.M. (ed): Controversies in the Management of Lymphomas ISBN Humphrey G.B., Grindey G.B. (eds): Adrenal and Endocrine Tumors in Children ISBN DeCosse 1.1., Sherlock P. (eds): Clinical Management of Gastrointestinal Cancer ISBN Catalona W.1., RatliffT.L. (eds): Urologic Oncology ISBN Santen R.l., Manni A. (eds): Diagnosis and Management of Endocrine-Related Tumors ISBN Costanzi 1.1. (ed): Clinical Management of Malignant Melanoma ISBN X Wolf G.T. (ed): Head and Neck Oncology ISBN Alberts D.S., Surwit E.A. (eds): Ovarian Cancer ISBN Muggia F.M. (ed): Experimental and Clinical Progress in Cancer Chemotherapy ISBN Higby D.l. (ed): Issues in Supportive Care of Cancer Patients ISBN Surwit E.A., Alberts D.S. (eds): Cervix Cancer ISBN lacobs e. (ed): Cancers of the Head and Neck ISBN MacDonald 1.S. (ed): Gastrointestinal Oncology ISBN RatliffT.L., Catalona W.l. (eds): Genitourinary Cancer ISBN Nathanson L. (ed): Basic and Clinical Aspects of Malignant Melanoma ISBN Muggia F.M. (ed): Concepts, Clinical Developments, and Therapeutic Advances in Cancer Chemotherapy ISBN Frankel A.E. (ed): Immunotoxins ISBN Bennett 1.M., Foon K.A. (eds): Immunologic Approaches to the Classification and Management of Lymphomas and Leukemias ISBN Osborne e.k. (ed): Endocrine Therapies in Breast and Prostate Cancer ISBN X Lippman M.E., Dickson R. (eds): Breast Cancer: Cellular and Molecular Biology ISBN Kamps W.A., Humphrey G.B., Poppema S. (eds): Hodgkin's Disease in Children: Controversies and Current Practice ISBN Muggia F.M. (ed): Cancer Chemotherapy: Concepts, Clinical Investigations and Therapeutic Advances ISBN Nathanson L. (ed): Malignant Melanoma: Biology, Diagnosis, and Therapy ISBN Pinedo H.M., Verweij 1. (eds): Treatment of Soft Tissue Sarcomas ISBN Hansen H.H. (ed): Basic and Clinical Concepts of Lung Cancer ISBN Lepor H., RatliffT.L. (eds): Urologic Oncology ISBN Benz e., Liu E. (eds): Oncogenes ISBN Ozols R.F. (ed): Drug Resistance in Cancer Therapy ISBN Surwit E.A., Alberts D.S. (eds): Endometrial Cancer ISBN Champlin R. (ed): Bone Marrow Transplantation ISBN Goldenberg D. (ed): Cancer Imaging with Radiolabeled Antibodies ISBN lacobs e. (ed): Carcinomas of the Head and Neck ISBN Lippman M.E., Dickson R. (eds): Regulatory Mechanisms in Breast Cancer: Advances in Cellular and Molecular Biology of Breast Cancer ISBN Nathanson L. (ed): Maligant Melanoma: Genetics, Growth Factors, Metastases, and Antigens ISBN Sugarbaker P.H. (ed): Management of Gastric Cancer ISBN Pinedo H.M., Verweij 1., Suit H.D. (eds): Soft Tissue Sarcomas: New Developments in the Multidisciplinary Approach to Treatment. ISBN Ozols R.F. (ed): Molecular and Clinical Advances in Anticancer Drug Resistance ISBN Muggia F.M. (ed): New Drugs, Concepts and Results in Cancer Chemotherapy ISBN Dickson R.B., Lippman M.E. (eds): Genes, Oncogenes and Hormones: Advances in Cellular and Molecular Biology of Breast Cancer. ISBN Humphrey G.B., Schraffordt Koops H., Molenaar W.M., Postma A., (eds): Osteosarcoma in Adolescents and Young Adults: New Developments and Controversies. ISBN Benz e.e., Liu E.T. (eds): Oncogenes and Tumor Suppressor Genes in Human Malignancies. Freireich E.l, Kantarjian H. (eds): Leukemia: Advances in Research and Treatment.
3 LEUKEMIA: ADVANCES IN RESEARCH AND TREATMENT Edited by EMIL J FREIREICH The University of Texas M.D. Anderson Cancer Center and HAGOP KANTARJIAN The University of Texas M.D. Anderson Cancer Center SPRINGER SCIENCE+BUSINESS MEDIA, LLC
4 Leukemia: advances in research and treatment/ediled by Emil J Freireich and Hagop Kantarjian. p. cm.-(cancer trealmenl and research ; CfAR 64) IncJudes bibliographical references and index. ISBN ISBN (ebook) DOI / Leukemia. 2. Genetic transformation. 1. Freireich, Emil J, II. Kantarjian, Hagop, III. Series: Cancer treatment and research ; v. 64. [DNLM: 1. Leukemia-therapy. WI CA693 v. 64 // WH 250 L6514] RC643.L '419-dc20 DNLMIDLC for Library of Congress CIP Copyright 1993 by Springer Science+Business Media New York Originally published by Kluwer Academic Publishers in 1993 Softcover reprint ofthe hardcover ISi editian 1993 AII rights reserved. No part of this publication may be reproduced, slored in a retrieval system or transmitted in any farm ar by any means, mechanical, photocopying, recording, or othelwise, withoul the prior wriuen permission of the publisher, Springer Science+Business Media, LLC. Cancer Treatment and Research is indexed in the National Library of Medicine MEDLARS System. Printed on acid free paper.
5 Table of Contents List of Contributors Preface VB Xl 1. All trans retinoic acid as a targeting drug for differentiation therapy in acute promyelocytic leukemia LAURENT DEGOS 2. Hairy cell leukemia: New understanding of biology and treatment ALAN SAVEN, LAWRENCE D. PIRO, CARLOS J. CARRERA, DENNIS A. CARSON, and ERNEST BEUTLER 3. Uses of polymerase chain reaction in leukemia: Detection of minimal residual disease and identification of novel genetic mutations MING-SHENG LEE and SANFORD A. STASS 4. The cell surface receptor encoded by the proto-oncogene KIT and its ligand ERNEST A. MCCULLOCH and M.D. MINDEN 5. Human T-cell lymphoma/leukemia retroviruses and malignancy MICHAEL P. SHERMAN, DIPAK K. DUBE, NITIN K. SAKSENA, and BERNARD J. POIESZ 6. Fludarabine phosphate in the treatment of chronic lymphocytic leukemia: Biology, clinical impact, and future directions L.E. ROBERTSON and MICHAEL J. KEATING v
6 7. The role of immunotherapy in the treatment of acute myeloblastic leukemia: From allogeneic bone marrow transplantation to the application of interleukin H. GRANT PRENTICE, IAN D. MACDONALD, and MICHAEL D. HAMON 8. Detection of minimal residual disease in ALL MIRIAM DEANE and A. VICTOR HOFFBRAND 9. Cytokines and myeloid-specific genes: Patterns of expression and possible role in proliferation and differentiation of acute myelogenous leukemia cells MICHAEL LUBBERT and ROLAND MERTELSMANN 10. The immunological treatment of human marrow in vitro in transplant biology JOHN G. GRIBBEN and LEE M. NADLER 11. Monoclonal antibodies in the treatment of myelogenous leukemias DAVID A. SCHEINBERG 12. Prognosis and therapy of myelodysplastic syndromes ELIHU H. ESTEY 13. Multidrug resistance in leukemia DANNY RISCHIN and VICTOR LING The molecular pathogenesis of the Philadelphia-positive leukemias: Implications for diagnosis and therapy RICHARD A. VAN ETTEN Index vi
7 List of Contributors ERNEST BEUTLER, M.D., Department of Molecular & Experimental Medicine, Scripps Clinic & Research Foundation Calfornia at North Torrey Pines Road, La Jolla, CA 92037, U.S.A. CARLOS J. CARRERA, M.D., Department of Medicine, University of Calfornia at San Diego, 9500 Gilman Drive, La Jolla, CA , U.S.A. DENNIS A. CARSON, M.D., Department of Medicine, Clinical Sciences Bidg. University of Calfornia at San Diego, 9500 Gilman Drive, La Jolla, CA , U.S.A. MIRIAM DEANE, M.B., M.R.C.P., Department of Hematology, Royal Free Hospital School of Medicine, Pond St., Hampstead, London NW3 2QG, U.K. LAURENT DEGOS, M.D., PH.D., Institut Universitaire D'Hematologie. Hopital Saint-Louis 1, Avenue Claude Vellefaux, Paris Cedex 10, France DIPAK K. DUBE, PH.D., D.SC., Department of Medicine, SUNY Health Science Center, 750 E. Adams Street, Syracuse, NY 13210, U.S.A. ELIHU H. ESTEY, M.D., Department of Hematology, The University of Texas, M.D. Anderson Cancer, Center 1515 Holcombe Boulevard-Box 61, Houston, TX 77030, U.S.A. JOHN G. GRIBBEN, M.D., PH.D., Division of Tumor Immunology, Dana Farber Cancer Institute, 44 Binney Street Boston, MA U.S.A. MICHAEL D. HAMON, M.R.C.P., M.R.C.PATH, Department of Hematology, Royal Free Hospital School of Medicine, Pond St.. Hampstead, London NW3 2QG, U.K. VII
8 A. VICTOR HOFFBRAND, D.M., F.R.C.P., F.R.C.PATH, D.SC., Department of Hematology, Royal Free Hospital School of Medicine, Pond St., Hampstead, London NW3 2QG, U.K. MICHAEL J. KEATING, M.D., Associate VIP For Clinical Investigations, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard-Box 38, Houston, TX 77030, U.S.A. MING-SHENG LEE, M.D., The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard-Box 72, Houston, TX 77030, U.S.A. VICTOR LING, PH.D., The Ontario Cancer Institute, 500 Sherbourne Street, Toronto, Ontario, Canada M4X 1K9 MICHAEL LOBBERT, M.D., University Medical Center, Department Medicine One, Hematology/Oncology, Hugstetter Street 55, 7800 Freiburg, Germany IAN D. MACDONALD, M.B., C.H.B., M.R.C.P., Department of Hematology, Royal Free Hospital School of Medicine, Pond St., Hampstead, London NW3 2QG, U.K. ERNEST A. MCCULLOCH, M.D., Ontario Cancer Institute, 500 Sherbourne Street, Toronto, Ontario, Canada M4X lk9 Sabbatical Address: The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd.-Box 72, Houston, TX 77030, U.S.A. ROLAND MERTELSMANN, M.D., PH.D. University Medical Center, Department Medicine One, Hematology/Oncology Hugstetter Street 55, 7800 Freiburg, Germany M.D. MINDEN, M.D., PH.D., Ontario Cancer Institute 500 Sherbourne Street, Toronto, Ontario, Canada M4X 1K9 LEE M. NADLER, M.D., Division of Tumor Immunology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, U.S.A. LA WRENCE D. PIRO, M.D., Department of Molecular & Experimental Medicine, Scripps Clinic & Research Foundation, North Torrey Pines Road, La Jolla, CA 92037, U.S.A. BERNARD J. POIESZ, M.D., Department of Medicine SUNY Health Science Center, 750 E. Adams Street, Syracuse, NY 13210, U.S.A. viii
9 H. GRANT PRENTICE, M.B., F.R.C.P., F.R.C.PATH, Department of Hematology, Royal Free Hospital School of Medicine, Pond St., Hampstead, London NW3 2QG, U.K. DANNY RISCHIN, M.B.B.S., F.R.A.C.P., The Ontario Cancer Institute, 500 Sherbourne Street, Toronto, Ontario, Canada M4X lk9/current address: Peter MacCallum Cancer Institute, 481 Little Lonsdale St., Melbourne, Victoria, 3000, Australia L.E. ROBERTSON, M.D., The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard-Box 61, Houston, TX 77030, U.S.A. NITIN K. SAKSENA, PH.D., Department of Medicine, SUNY Health Science Center, 750 E. Adams Street, Syracuse, NY U.S.A. ALAN SA VEN, M.D., Department of Molecular & Experimental Medicine, Scripps Clinic & Research Foundation, North Torrey Pines Road, La Jolla, CA 92037, U.S.A. DAVID A. SCHEINBERG, M.D., PH.D., Chief, Leukemia Service, Director, Cell Marker Laboratory Memorial Hospital, Head, Hematopoietic Cancer, Immunochemistry Laboratory, Molecular Pharmacology and Therapeutics Program, Sloan-KeHering Institute, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10021, U.S.A. MICHAEL P. SHERMAN, PH.D., Department of Medicine, SUNY Health Science Center, 750 E. Adams Street, Syracuse, NY 13210, U.S.A. SANFORD A. STASS, M.D., The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard-Box 72, Houston, TX U.S.A. RICHARD A. VAN ETTEN, M.D., PH.D., Harvard Medical School The Center for Blood Research 800 Huntington Avenue, Boston, MA 02115, U.S.A. IX
10 Preface Leukemia continues to offer the scientist a unique opportunity to gain new knowledge about malignant transformation. As a result, a multiauthored volume devoted to advances that have occurred over the last seven years provides the reader with important new understanding of leukemia, but perhaps even more importantly, predicts for analogous new developments in the other malignant diagnoses. Therefore, a volume devoted to advances in leukemia should represent the cutting edge of cancer research. In this volume the editors have had a relatively unique success rate in recruiting the authors who have made the signal observations in the areas that they cover in their individual chapters. The chapters in this volume have excellent up-to-data analyses of the state of our knowledge prepared by premier scientists in these fields. In the opening chapter, Dr. Degos summarizes the current state of our knowledge of the first molecular chemotherapy-the remission-inducing effect of all trans retinoic acid in the disease acute promyelocytic leukemia, which is identified by the 15;17 translocation. This represents the first of what will almost certainly be a major new approach to the treatment of malignant disease. Dr. Degos and his group were the first to identify the rearrangement in this unique disease and have provided leadership in the understanding of the nature of the differentiating effect of this important treatment. In the second chapter, the group at Scripps Clinic headed by Drs. Beutler and Carson summarizes the intellectual basis for a new and highly effective treatment, chlorodeoxyadenosine, in the management of hairy cell leukemia. This group was able to move from the chemistry laboratory through the regulatory jungles into clinical trial, all within a single institution, and have brought a new treatment to practical reality, which in itself is an achievement. This has opened an important new field for therapeutic intervention, because there are multiple adenosine analogues that operate not by suppressing DNA synthesis but by initiating apoptosis through depletion of intracellular NAD. This intervention is equally effective in cells that are not in the S phase of DNA synthesis. The third chapter, prepared by Dr. M.S. Lee on the polymerase chain reaction, elaborates the current state of the usefulness of this extraordinary laboratory procedure. Xl
11 Dr. Lee was the first to apply the polymerase chain reaction to the detection of residual disease in the 14;18 translocation and subsequently was among the first to utilize reverse transcription and polymerase chain reaction amplification of cdna for the detection of residual transcripts of the BCR/ abl gene in chronic granulocytic leukemia. In this chapter we have an authoritative portrayal of the usefulness of this important new technology. The fourth chapter was written by Drs. McCulloch and Minden. It deals with dramatic new information about the stem cell growth factor and the KIT ligand. Dr. McCulloch was the first to show the important relationship between genetically developed mice having deficiency of the KIT on one hand and the Steel factor on the other. In his elegant presentation, he summarizes not only the current state of our knowledge but also the potential importance of this new field for the understanding of leukemia cell biology and tumor biology. The fifth contribution, by Drs. Sherman, Dube, Saksena, and Poiesz, deals with the increasingly important relationship of human T-cell lymphoma/leukemia oncornaviruses and malignancies. Dr. Poiesz made pioneering observations in this important field and has continued to play a leadership role in uncovering the growing frequency of these malignancies in the intravenous drug abuser community, in the volunteer blood donor supply, and in the other human malignancies. In this chapter, the authors summarize the biological and molecular biological properties of this group of retroviruses. In the next chapter, Drs. Robertson and Keating summarize our current knowledge of the effect of f1udarabine on the natural history and biology of chronic lymphocytic leukemia. Dr. Keating and the group at Anderson were the first to recognize that it would be possible to achieve major hematological remissions in chronic lymphocytic leukemia with this drug. In a series of brilliantly conceived studies, they have elaborated on the biology of this treatment and the increase in our understanding of chronic lymphocytic leukemia that has resulted from this treatment advance. In chapter 7, Dr. Prentice reviews the important biological knowledge that emanated from observations of graft-versus-ieukemia effects in the allogeneic transplant setting. He summarizes our current knowledge of the effect of IL-2 in the posttransplant setting and the potential of Interleukin 2 for further enhancing host effects against malignancy. In chapter 8, Drs. Deane and Hoffbrand explore innovative approaches to the measurement of minimal residual disease in lymphoid malignancies, particularly acute lymphoblastic leukemia. This is a comprehensive review of the available strategies for measuring minimal residual disease, and Dr. Hoffbrand presents original data relating to the predicted value of the testing developed in his laboratory on the stability of remission in lymphoblastic disease, which is an extremely promising area of clinical research. In the next chapter, Drs. Lubbert and Mertelsmann review the molecular biology of the hematopoietic growth factors and the clinical studies to date that indicate the place of these growth factors in the therapeutic armamentarium and in the understanding of the biology of leukemia. Their xii
12 group has played a pioneering role in evaluating these important new growth factors, which are increasingly important not only in supportive therapy but in the therapy of leukemic disorders. In chapter 10, Drs. Gribben and Nadler review the current state of the treatment of autologous bone marrow in vitro before utilizing it to support patients after intensive therapy for their underlying disease. This group has pioneered the development of effective techniques for improving the autologous marrow strategy in the treatment of leukemia and potentially for other forms of malignancies. In a scholarly and informed chapter, Dr. Scheinberg follows with a significant summary not only of his original work on monoclonal antibody therapy for the myeloid leukemias but also of the current state of our knowledge of this field. In chapter 12, Dr. Estey reviews our current knowledge of the myelodysplastic syndromes. It seems clear that these complex and multifaceted disorders are increasing in frequency, particularly in the group of patients who have had prior cytotoxic damage to their bone marrow. Heretofore, they have been classified by the FAB (French, American, British) classification system, which has been extremely useful. But the new knowledge of cytogenetics and cell biology in vitro and the effects of intensive therapy on the natural history of these diseases have forced reexamination of both the prognostic criteria and treatment effects. Again, Dr. Estey has pioneered in this field and provides an excellent summary of the current state of our knowledge. In chapter 13, Drs. Rischin and Ling review the multidrug resistance gene in leukemia. Dr. Ling not only is a pioneer in this field but also has continued to make signal contributions to it that are elegantly summarized in this authoritative chapter. In the final chapter, Dr. Richard Van Etten, who was the first person to successfully transfect the BCRlabl gene into myeloid hematopoietic stems cells and demonstrate that a chronic granulocytic-like disease can result in the mouse, summarizes in a scholarly, thorough, and elegant way the biological significance of the BCRlabl gene and its impact on our understanding of molecular genetics in malignancies. In summary, we feel that this multi authored text has the relatively unique characteristic of including in a single volume work of the leading contributors to their respective fields and covering what the editors feel are the major advances in our knowledge of the biology and therapy of leukemia over the last seven years. There are important areas that could not be included, but the excellence of the contributions of these authors far exceeds any deficiency that the editors may have introduced by overlooking other important advances. Emil J Freireich, M.D., D.Sc. (Hon.) Hagop Kantarjian, M.D. Editors Xlii
13 LEUKEMIA: ADVANCES IN RESEARCH AND TREATMENT
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