M
ODERN
H
EMATOLOGY
C
ONTEMPORARY
H
EMATOLOGY
Modern Hematology: Biology and Clinical Management, Second Edition,
edited by REINHOLD MUNKER, ERHARD HILLER, JONATHAN GLASS,AND
RONALD PAQUETTE, 2007
Stem Cell Transplantation for Hematologic Malignancies, edited by ROBERT
J. SOIFFER, 2004
Biologic Therapy of Leukemia, edited by MATT KALAYCIO, 2003
Chronic Lymphocytic Leukemia:Molecular Genetics, Biology, Diagnosis, and Management, by GUY B. FAGUET,2003
Modern Hematology: Biology and Clinical Management,byREINHOLD
MUNKER, ERHARD HILLER,AND RONALD PAQUETTE, 2000
Red Cell Transfusion: A Practical Guide, edited by MARION E. REID AND
SANDRA J. NANCE, 1998
M
ODERN
H
EMATOLOGY
Biology and Clinical Management, Second Edition
Edited by
R
EINHOLD
M
UNKER
,
MD
Louisiana State University, Shreveport, LA
E
RHARD
H
ILLER
,
MD
Ludwigs-Maximilians Universität, Munich, Germany
J
ONATHAN
G
LASS
,
MD
Feist Weiller Cancer Center, Louisiana State University,
Shreveport, LA
R
ONALD
P
AQUETTE
,
MD
University of California Los Angeles, Los Angeles, CA
Foreword by
H. P
HILLIP
K
OEFFLER
,
MD
© 2007 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512
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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 care-fully 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 conse-quences 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. f
ANSI Z39.48-1984 (American National Standards Institute) Permanence of Paper for Printed Library Materials. Production Editor: Tracy Catanese
Cover Illustration: Figure 3 from Chapter 9, “Acute Myelogenous Leukemias” by Reinhold Munker. 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 $30.00 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: [978-1-58829-557-6 • 1-58829-557-5/07 $30.00].
Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 e-ISBN-13: 978-1-59745-149-9
e-ISBN-10: 1-59745-149-5
Library of Congress Cataloging-in-Publication Data
Modern hematology : biology and clinical management / edited by Reinhold Munker ... [et al.]. -- 2nd ed.
p. ; cm. -- (Contemporary hematology)
Rev. ed. of: Modern hematology / Reinhold Munker, Erhard Hiller, Ronald Paquette. c2000. Includes bibliographical references and index.
ISBN-13: 978-1-58829-557-6 (alk. paper); ISBN-10: 1-58829-557-5 (alk. paper)
1. Blood--Diseases. 2. Hematology. I. Munker, Reinhold. II. Munker, Reinhold. Modern hematology. III. Series.
[DNLM: 1. Hematologic Diseases. 2. Hematologic Neoplasms. WH 120 M689 2006] RC633.M866 2006
616.1'5--dc22
F
OREWORD
Technological advances have quickly propelled hematology forward; for example: microarray expression analyses; single-nucleotide polymorphism (SNP) chips (platforms to look at genomic changes); sophisticated fluorescent in situ
hybridization; newly identified cell surface antigens associated with various dis-eases and cell types; understanding of transcription factors (engines of prolifera-tion and differentiaprolifera-tion of hematopoietic cells); and more complete knowledge of chromosomal changes, mutations and amplifications associated with various hematological malignancies. These advances have been the engines for better diagnosis and classification of hematopoietic disorders. Furthermore, a variety of new therapeutic approaches have come to the forefront, such as targeted therapies (thyrosine kinase inhibitors) for myeloproliferative disorders; lenalidomide for myelodysplastic syndrome (MDS) and multiple myeloma; demethylating agents for MDS and myeloid leukemia, as well as, humanized monoclonal antibodies for lymphomas. Many of these advancements have occurred since the first edition of
Modern Hematology: Biology and Clinical Management by Dr. Rienhold Munker and colleagues was published 6 years ago.
This new edition, edited by Drs. Reinhold Munker, Erhard Hiller, Jonathan Glass, and Ronald Paquette, provides in clear terms an understanding of the cellular physiology, immunology, and molecular biology of hematopoietic dis-orders. It gives new diagnostic methodologies and guides the health care worker to practical approaches to the diagnoses and management of these blood disor-ders. The book covers all of the major hematopoietic diseases and a number of the rare diseases as they interface with new scientific knowledge. It has excellent “how to” tables providing dosage and time schedules of different chemothera-peutic agents, as well as clearly defined tables to aid in diagnosis and prognosis.
Modern Hematology: Biology and Clinical Management, Second Edition is a fine montage of applied research and practical approaches to diagnosis and management of our patients. The book is ideal for the house officers, fellows in training, interested scientists, as well as the practicing hematologist.
H. Phillip Koeffler, MD
P
REFACE
In the 6 years since the publication of Modern Hematology: Biology and Clinical Management, major advances in the understanding, diagnosis, and treat-ment of blood disorders have again been made. Molecular studies are now used on a daily basis to diagnose a variety of hematological disorders and to guide their treatment. Targeted therapies, such as kinase inhibitors in myeloprolifera-tive disorders and humanized monoclonal antibodies for lymphomas, have trans-formed the treatment approach to these diseases. Peripheral blood and even umbilical cord blood are now routinely used as sources of stem cells for trans-plantation. The growing use of nonmyeloablative transplantation emphasizes immunotherapy over cytotoxic chemotherapy. These advances motivated us to updateModern Hematology: Biology and Clinical Management with the latest clinical and scientific developments in hematology. We welcome the contribu-tions of new authors. The growing use of databases prompted us to add an overview of printed and electronic resources for hematologists.
Modern Hematology: Biology and Clinical Management, Second Edition
brings together facts, concepts, and protocols important for the practice of hema-tology. In 23 concise chapters, all major blood diseases are covered; rarer dis-eases are discussed if they are of scientific interest. The first two chapters introduce the reader to the scientific basis of blood disorders. As in the previous edition, each chapter is illustrated by tables, figures, and a selection of color plates. Our text is ideal for residents or fellows in training. However, students, physicians in other specialties, and even pure scientists may take advantage of our book both as a reference and a study guide. We hope that ultimately, all patients with benign and malignant blood disorders will benefit from the publi-cation of Modern Hematology: Biology and Clinical Management, Second Edition. Reinhold Munker, MD Erhard Hiller, MD Jonathan Glass, MD Ronald Paquette, MD vii
ix
C
ONTENTS
Foreword ... v
Preface ... vii
Contributors ... xi
Color Plates ... xiii
1 Basic Biology of Hemopoiesis ... 1
Reinhold Munker 2 Molecular Biology and Cytokines ... 19
Reinhold Munker and Amanda Sun 3 Supportive Care in Hematology ... 41
John Hiemenz and Reinhold Munker 4 Transplantation of Stem Cells From Bone Marrow, Peripheral Blood, and the Umbilical Cord ... 63
Ronald Paquette and Reinhold Munker 5 Anemias: General Considerations and Microcytic, and Megaloblastic Anemias... 83
Reinhold Munker 6 Hemolytic Anemias ... 101
Reinhold Munker, Ali Mansouri, Snehalata C. Gupte, and Vishwas Sakhalkar 7 Leukocytosis, Leukopenia, and Other Reactive Changes of Myelopoiesis ... 127
Reinhold Munker 8 The Myeloproliferative Syndromes ... 137
Ronald Paquette, Erhard Hiller, and Reinhold Munker 9 Acute Myelogenous Leukemias ... 155
Reinhold Munker 10 Acute Lymphoblastic Leukemias ... 173
Reinhold Munker and Vishwas Sakhalkar 11 Myelodysplastic Syndromes ... 195
Ronald Paquette and Reinhold Munker 12 Aplastic Anemias ... 207
13 Lymphocytosis, Lymphocytopenia, Lymphadenopathy,
and Splenomegaly ... 217
Reinhold Munker
14 Hodgkin’s Lymphoma ... 225
Erhard Hiller and Reinhold Munker
15 The Non-Hodgkin’s Lymphomas ... 237
Reinhold Munker, Jay Marion, Gang Ye, and Martin H. Dreyling
16 Multiple Myeloma and Related Paraproteinemias ... 271
Jonathan Glass and Reinhold Munker
17 Congenital and Acquired Immunodeficiencies ... 295
Vishwas Sakhalkar and Reinhold Munker
18 Infections Relevant to Hematology ... 315
Reinhold Munker
19 Basic Principles of Hemostasis ... 327
Erhard Hiller
20 Bleeding Disorders ... 347
Erhard Hiller
21 Thrombophilia, Thromboembolic Disease,
and Antithrombotic Therapy ... 381
Erhard Hiller
22 Transfusion Medicine and Immunohematology ... 401
Grace C. Tenorio, Snehalata C. Gupte, and Reinhold Munker
23 Storage Disorders in Hematology ... 433
Reinhold Munker
APPENDICES
1 Glossary of Cytostatic Drugs and Targeted Therapies ... 441 2 CD Nomenclature for Human Leukocyte Antigens ... 455 3 Laboratory Values ... 463 4 Program Requirements for Residency
and Fellowship Education in Hematology ... 465 5 Databases in Hematology ... 467 Index ... 475
xi
C
ONTRIBUTORS
MICHAEL COCKERHAM,PharmD • Associate Professor of Clinical Pharmacy,
Louisiana State University, Shreveport, LA
MARTIN H. DREYLING,MD • Associate Professor of Medicine,
Ludwigs-Maximilians Universität, Munich, Germany
JONATHAN GLASS,MD • Professor of Medicine and Chief, Feist Weiller Cancer
Center, Louisiana State University, Shreveport, LA
SNEHALATA C. GUPTE,PhD • Director, Surat Blood Transfusion Center, Surat,
India
JOHN HIEMENZ,MD • Professor of Medicine, Louisiana State University,
Shreveport, LA
ERHARD HILLER,MD• Professor of Medicine, Ludwigs-Maximilians
Universität, Munich, Germany
H. PHILLIP KOEFFLER,MD• Division of Hematology/Oncology, Cedars Sinai
Medical Center, Los Angeles, CA
ALI MANSOURI,MD • Professor of Medicine, Louisiana State University and
Chief, Division of Hematology/Oncology, VA Medical Center, Shreveport, LA
JAY MARION,MD • Associate Professor of Medicine, Louisiana State
University, Shreveport, LA
REINHOLD MUNKER,MD • Associate Professor of Medicine, Louisiana State
University, Shreveport, LA
RONALD PAQUETTE,MD • Associate Professor of Medicine, University of
California Los Angeles, Los Angeles, CA
VISHWAS SAKHALKAR,MD • Assistant Professor of Pediatrics, Louisiana State
University, Shreveport, LA
AMANDA SUN,MD,PhD • Assistant Professor of Medicine, Louisiana State
University, Shreveport, LA
GRACE C. TENORIO,MD • Assistant Professor of Pathology, Louisiana State
University, Shreveport, LA
C
OLOR
P
LATES
xiii
Color plates 1–23 appear in an insert following p. 242.
Plate 1 Fig. 5.2, Megaloblastic Erythroblasts; for full caption, see p. 94. Plate 2 Fig. 7.1, Granulocytes; for full caption, see p. 129.
Plate 3 Fig. 7.2, Döhle Bodies; for full caption, see p. 129. Plate 4 Fig. 9.3, APL, Myeloid Blasts; for full caption, see p. 162.
Plate 5 Fig. 9.4, Peroxidase Stain, AML Blasts; for full caption, see p. 162. Plate 6 Fig. 9.5, Fluorescent in situ Hybridization in APL; for full caption,
see p. 163.
Plate 7 Fig. 10.2, ALL Lymphoblast; for full caption, see p. 179. Plate 8 Fig. 10.3, Blasts of B-ALL; for full caption, see p. 179.
Plate 9 Fig. 11.1, Dysplastic Changes in Erythropoiesis; for full caption,
see p. 199.
Plate 10 Fig. 11.2, Ringed Sideroblasts, MDS; for full caption, see p. 200. Plate 11 Fig. 12.1, Aplastic Anemia, Histology; for full caption, see p. 212. Plate 12 Fig. 12.2, Normal Bone Marrow, Histology; for full caption, see p.
212.
Plate 13 Fig. 13.3, Howell Jolly Bodies; for full caption, see p. 222. Plate 14 Fig. 14.2, Lymph Node, Hodgkin’s; for full caption, see p. 230. Plate 15 Fig. 15.1, Lymph Node, Non-Hodgkin’s; for full caption, see p. 243. Plate 16 Fig. 15.2, Follicle Center Lymphoma; for full caption, see p. 249. Plate 17 Fig. 15.3, CLL Morphology; for full caption, see p. 254.
Plate 18 Fig. 15.4, PLL Morphology; for full caption, see p. 257.
Plate 19 Fig. 15.5, Adult T-Cell Leukemia, Lymphoma; for full caption, see
p. 258.
Plate 20 Fig. 15.6, Hairy Cell Leukemia; for full caption, see p. 262.
Plate 21 Fig. 16.2, Multiple Myeloma, Dense Infiltrate of Neoplastic Plasma Cells; for full caption, see p. 280.
Plate 22 Fig. 16.3, Multiple Myeloma, Bone Marrow; for full caption, see p. 280.
