MODERN HEMATOLOGY SECOND EDITION

MODERN HEMATOLOGY SECOND EDITION

CONTEMPORARY HEMATOLOGY Gary J. Schiller, MD, SERIES EDITOR 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, by REINHOLD MUNKER, ERHARD HILLER, AND RONALD PAQUETTE, 2000 Red Cell Transfusion: A Practical Guide, edited by MARION E. REID AND SANDRA J. NANCE, 1998

MODERN HEMATOLOGY Biology and Clinical Management, Second Edition Edited by REINHOLD MUNKER, MD Louisiana State University, Shreveport, LA ERHARD HILLER, MD Ludwigs-Maximilians Universität, Munich, Germany JONATHAN GLASS, MD Feist Weiller Cancer Center, Louisiana State University, Shreveport, LA RONALD PAQUETTE, MD University of California Los Angeles, Los Angeles, CA Foreword by H. PHILLIP KOEFFLER, MD Cedars-Sinai Medical Center, Los Angeles, CA

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FOREWORD 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 diseases and cell types; understanding of transcription factors (engines of proliferation and differentiation 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., Erhard Hiller, Jonathan Glass, and Ronald Paquette, provides in clear terms an understanding of the cellular physiology, immunology, and molecular biology of hematopoietic disorders. It gives new diagnostic methodologies and guides the health care worker to practical approaches to the diagnoses and management of these blood disorders. 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 chemotherapeutic 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 v

PREFACE In the 6 years since the publication of Modern Hematology: Biology and Clinical Management, major advances in the understanding, diagnosis, and treatment 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 myeloproliferative disorders and humanized monoclonal antibodies for lymphomas, have transformed the treatment approach to these diseases. Peripheral blood and even umbilical cord blood are now routinely used as sources of stem cells for transplantation. The growing use of nonmyeloablative transplantation emphasizes immunotherapy over cytotoxic chemotherapy. These advances motivated us to update Modern Hematology: Biology and Clinical Management with the latest clinical and scientific developments in hematology. We welcome the contributions 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 hematology. In 23 concise chapters, all major blood diseases are covered; rarer diseases 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 publication of Modern Hematology: Biology and Clinical Management, Second Edition., MD Erhard Hiller, MD Jonathan Glass, MD Ronald Paquette, MD vii

CONTENTS Foreword... v Preface... vii Contributors...xi Color Plates... xiii 1 Basic Biology of Hemopoiesis... 1 2 Molecular Biology and Cytokines... 19 and Amanda Sun 3 Supportive Care in Hematology... 41 John Hiemenz and 4 Transplantation of Stem Cells From Bone Marrow, Peripheral Blood, and the Umbilical Cord... 63 Ronald Paquette and 5 Anemias: General Considerations and Microcytic, and Megaloblastic Anemias... 83 6 Hemolytic Anemias...101, Ali Mansouri, Snehalata C. Gupte, and Vishwas Sakhalkar 7 Leukocytosis, Leukopenia, and Other Reactive Changes of Myelopoiesis...127 8 The Myeloproliferative Syndromes...137 Ronald Paquette, Erhard Hiller, and 9 Acute Myelogenous Leukemias...155 10 Acute Lymphoblastic Leukemias...173 and Vishwas Sakhalkar 11 Myelodysplastic Syndromes...195 Ronald Paquette and 12 Aplastic Anemias...207 Ronald Paquette and ix

x Contents 13 Lymphocytosis, Lymphocytopenia, Lymphadenopathy, and Splenomegaly...217 14 Hodgkin s Lymphoma...225 Erhard Hiller and 15 The Non-Hodgkin s Lymphomas...237, Jay Marion, Gang Ye, and Martin H. Dreyling 16 Multiple Myeloma and Related Paraproteinemias...271 Jonathan Glass and 17 Congenital and Acquired Immunodeficiencies...295 Vishwas Sakhalkar and 18 Infections Relevant to Hematology...315 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 23 Storage Disorders in Hematology...433 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

CONTRIBUTORS 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 GANG YE, MD Louisiana State University, Shreveport, LA xi

COLOR PLATES 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. Plate 23 Fig. 18.1, Infectious Mononucleosis; for full caption, see p. 317. xiii