Hematology

Basic Principles and Practice

8th Edition - December 2, 2022
Editors: Ronald Hoffman, Edward J. Benz, Leslie E. Silberstein, Helen Heslop, Jeffrey Weitz, Mohamed E. Salama
Language: English
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 7 3 3 8 8 - 5
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 2 8 3 4 4 - 4

Extensively revised, comprehensive content from leading global contributors ensures that Hematology, 8th Edition, remains your #1 choice for expert guidance in all areas of this… Read more

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Extensively revised, comprehensive content from leading global contributors ensures that Hematology, 8th Edition, remains your #1 choice for expert guidance in all areas of this rapidly advancing subspecialty. This edition reflects the numerous advances that are redefining the field and dramatically influencing new approaches to diagnosis, treatment, and outcomes. Well-illustrated and clinically focused, it details the basic science and clinical practice of hematology and hematopoietic cellular therapy—covering virtually all aspects of hematology in one definitive resource.

Covers all hematologic disorders, including comprehensive discussions of hematologic malignancies, individualized patient care, cell-based therapies, transplantation, transfusion medicine, hemostasis, thrombosis, and consultative hematology—in one convenient volume.
Provides state-of-the-art guidance from global experts at the forefront of the latest research and clinical practice.
Provides extensive updates throughout on basic science research, advances in molecular diagnostics, new drugs, immunotherapies, personalized medicine, laboratory medicine, transfusion medicine, stem cell transplantation, and clinical treatment for all hematologic malignancies and non-malignancies
Contains new chapters on gene editing; the impact of mitochondria on hematopoiesis; myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes; immunotherapy and management of its toxicities; transfusion medicine in sickle cell disease; principles of radiation therapy; and COVID-19, including complications of vaccination and its impact on the hematologic system.
Discusses many new advances in the field, including details and the future of gene therapy for hemophilia, gene editing for sickle cell disease and thalassemia, the evolution of cellular therapy, use of cells, transfusion medicine vs. protein therapy, gene sequencing, immunotherapy, and new targeted drugs.
Includes more decision-making algorithms for formulating diagnoses and personalized treatment plans for those highly complex disorders that require individualized approaches.
Addresses the effects of aging on hematopoiesis and on the manifestations of a variety of hematologic disorders.
Discusses cardio-oncology and its impact on the treatment of patients with hematologic disorders.
Presents relevant basic science as background for clinical application in later sections.
An eBook version is included with purchase. The eBook allows you to access all of the text, figures and references, with the ability to search, customize your content, make notes and highlights, and have content read aloud.

Instructions for Online Access
Cover image
Title page
Table of Contents
Any screen, Any time, Anywhere
Copyright
Dedication
Contributors
Preface
Part I: Molecular and Cellular Basis of Hematology
Chapter 1. Anatomy and Physiology of the Gene
Abstract
The Genetic View of the Biosphere: The Central Dogma of Molecular Biology
The Anatomy and Physiology of THE Gene
Regulation of Gene Expression
Molecular Genetic Methodologies Allowing the Isolation, Analysis, and Manipulation of Genes
DNA- and RNA-Based Therapeutics
Future Directions
Suggested Readings
Chapter 2. Epigenomics in Hematology
Abstract
Functional Chromatin Domains
Dna Methylation
Histones and Histone Variants
Covalent Histone Modifications
Transcription Factors
Chromatin Remodelers
Experimental Approaches in Epigenetics
Mechanisms of Disease
Epigenetic Therapies
Future Directions
Suggested Readings
Chapter 3. Genomic Approaches to Hematology
Abstract
Introduction
General Principles of Genomic Testing
Next-Generation Sequencing Technology
The Clinical Utility of Genomics in Hematologic Malignancies
The Clinical Utility of Genomics in Benign Hematology
Approaches to the Development of Molecular Testing
Suggested Readings
References
Chapter 4. Regulation of Gene Expression in Hematology
Abstract
Introduction
Regulation of Transcription
Regulation of RNA Processing: Capping, Splicing, and Polyadenylation
Nuclear Export of RNA
RNA Heterogeneity
Regulation of RNA Metabolism: Stability and Localization
Protein Synthesis
Protein Sorting
Protein Folding and Posttranslational Modifications
Protein Degradation
Conclusions
Suggested Readings
References
Chapter 5. Genome Editing
Abstract
Double-Stranded Dna Breaks: The Basis of Nuclease-Based Genome Editing
Base Editing
Other Genome Editing Systems
Using Engineered Nucleases to Initiate the Genome Editing Process
Genome Editing Using Only a Nuclease and Nonhomologous End-Joining Repair
A Broad Range of Genomic Changes by Homologous Recombination–Mediated Genome Editing
Genotoxicity Through Potential Off-Target Nuclease-Induced Double-Strand Breaks
Genome Editing as a Research Tool
Genome Editing as a Therapeutic Strategy
Ex Vivo Manufacturing of Therapeutic Cells
Therapeutic Genome Editing for Hematologic Diseases
Opportunities for Genome Editing in Vivo
Challenges to in Vivo Editing of Hematopoietic Stem Cells
Heritable Genome Editing
Suggested Readings
References
Chapter 6. Signaling Transduction and Metabolomics
Abstract
Signaling Transduction
Metabolomics and Control of Hematopoietic Cell Metabolism
Summary and Perspectives
Suggested Readings
Chapter 7. Protein Architecture: Relationship of Form and Function
Abstract
Amino Acids and the Peptide Bond
Future Directions
Suggested Readings
References
Chapter 8. Pharmacogenomics and Hematologic Diseases
Abstract
Variation in the Human Genome
Single-Nucleotide Polymorphisms
Single-Nucleotide Polymorphisms and Phenotypes
Structural Genomic Variants
Somatic Genomic Variants
Catalogs of Genomic Variants, Genotyping Platforms, and Genome-Wide Association Studies
Genetic Variations Influencing Drug Response: Pharmacogenetics–Pharmacogenomics–Pharmacoepigenomics
Optimization of Drug Therapy
Genetic Variations that Influence Drug Disposition and Effects
Drug Transporters
Genetic Variations Influencing Drug Targets
Adverse Drug Effects Presenting as Hematologic Disorders
Drug Development
Future Directions
Suggested Reading
References
Part II: Cellular Basis of Hematology
Chapter 9. Hematopoietic Stem Cell Biology
Abstract
Embryonic Origin of Hematopoietic Stem Cells
Definition and Characterization of Hematopoietic Stem Cells
Regulation of Hematopoietic Stem Cell Fate
Intrinsic Pathways
Hematopoietic Stem Cell Metabolism
Novel Growth Factors for Expanding Hematopoietic Stem Cells and Clinical Testing
Generating Hematopoietic Stem Cells from Pluripotent Stem Cells and by Reprogramming of Somatic Cells
Hematopoietic Stem Cell Regeneration
Hematopoietic Stem Cells and Malignancy (See Chapters 13 and 59Chapter. 13Chapter. 59Chapters 13 and 59)
Suggested Readings
References
Chapter 10. Mitochondria and Hematopoiesis
Abstract
Mitochondrial Structure and Function
Mitochondrial Diseases
Mitochondrial Regulation of Hematopoietic Stem Cell Fates
Interaction of Mitochondrial Network with the Bone Marrow Milieu Regulates Hematopoietic Stem Cell Fates
Mitochondrial and Bone Marrow Roles in Leukemic Stem Cells and Aged Hematopoietic Stem Cells
Mitochondrial and Epigenome Control Reprogramming of Hematopoietic Stem Cells
Concluding Remarks
References
Chapter 11. Cytokines, Chemokines, Other Growth Factors, and Their Receptors
Abstract
Introduction
Cytokines and Their Modifying Influences
Specifics of Growth-Modulating Factors
Colony-Stimulating Factors
Other Growth Modulating Proteins/Factors
Concluding Thoughts
Suggested Readings
References
Chapter 12. Role of Chemokines in Leukocyte Trafficking
Abstract
Chemokines
Signaling by Chemokine Receptors
Atypical Chemokine Receptors
Chemokine Interaction With Glycosaminoglycans
Leukocyte Entry Into Tissues
Leukocyte Migration Within Tissues
Leukocyte Exit from Tissues
Summary
Suggested Readings
References
Chapter 13. Stem Cell Model of Hematologic Diseases
Abstract
Cell-Of-Origin Studies in Hematologic Malignancies
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Myeloproliferative Neoplasms
Acute Lymphoblastic Leukemia
Mature B-Cell Malignancies
Chronic Lymphocytic Leukemia
Hairy Cell Leukemia
Diffuse Large B-Cell Lymphoma
Follicular Lymphoma
Conclusion
References
Chapter 14. Hematopoietic Microenvironment
Abstract
Evolution of the Niche Concept
Hematopoietic Microenvironment During Development
Adult Bone Marrow Microenvironment
Extrinsic Regulation of the Hematopoietic Stem Cell Niche
Lymphoid Niches
Erythroid Niches
Megakaryocytic Niches
Human Bone Marrow Microenvironment
Hematopoietic Microenvironment in Acute Leukemia and Myelodysplasia
Future Directions
References
Chapter 15. Cell Adhesion
Abstract
Adhesion Molecules
Extracellular Matrix Proteins
Integrins
Immunoglobulin-Like Receptors
Other Adhesion Receptors that Mediate Protein–Protein Interactions
Lectin Adhesion Receptors
Ligand Binding Versus Cell Adhesion
Regulation of Adhesion Receptors
Regulation of Synthesis
Regulation of Surface Expression
Regulation of Binding Affinity
Cell Signaling Through Adhesion Molecules
Cooperative Interactions Between Signaling and Adhesion Molecules
Platelet Adhesion, Aggregation, and Hemostasis
Suggested Readings
Chapter 16. Current Biology of Stem Cell Homing and Mobilization: Dynamic Interactions Between Hematopoietic Stem and Progenitor Cells and Their Surrounding Bone Marrow Microenvironment
Abstract
Introduction
Lessons from Steady-State Homeostatic Regulation of Hematopoietic Stem and Progenitor Cells
Medical Approaches Originating from Understanding Mechanisms that Regulate Physiological Hspc Trafficking, for the Sake of Curative Stem Cell Transplantation Protocols
Hematopoietic Stem and Progenitor Cell Homing
Hematopoietic Stem and Progenitor Cell Mobilization: A Dynamic Multi-Facet Process
Concluding Remarks
Acknowledgments
References
Chapter 17. Control of Cell Division
Abstract
The Cell Division Cycle
Signaling
Cyclins and Cyclin-Dependent Kinases
Cyclin-Dependent Kinase Inhibitors
Transcriptional Regulation: MYC, RB-E2F, and Dream/Muvb
Ubiquitination
Deoxyribonucleic Acid Replication
Mitosis
Cell Cycle Checkpoints
Special Hematology Cell Cycle Features
References
Chapter 18. Cell Death
Abstract
Core Apoptosis Pathways
The Intrinsic Apoptotic Pathway
Nonapoptotic Roles of Bcl-2 Family Proteins
The Death Receptor (Extrinsic) Pathway of Apoptosis
Nonapoptotic Forms of Cell Death
Cell Survival and Cell Death Pathways and Adaptive Responses to Stress
Clinical Applications
Preclinical Activity of Bcl2 Antisense and Bh3-Mimetics in Myeloid Malignancies
Clinical Development of Bh3-Mimetics for Myeloid Malignancies
Rationale for Use of Bh-3 Mimetics in Chronic Lymphocytic Leukemia
Clinical Development of Venetoclax for Chronic Lymphocytic Leukemia
Mechanisms of Resistance to Venetoclax in Chronic Lymphocytic Leukemia
Summary
Suggested Readings
References
Chapter 19. Aging and Hematopoiesis
Abstract
Aging
Hematopoietic Stem Cell Potential Declines With Aging
Clinical Manifestations
Clonal Hematopoiesis, Clonal Hematopoiesis of Indeterminate Potential, and Age-Related Clonal Hematopoiesis
Mechanisms of Hematopoietic Stem Cell Aging
Intrinsic Factors
Extrinsic Factors
Future Perspectives
References
Part III: Immunologic Basis of Hematology
Chapter 20. Dendritic Cell Biology
Abstract
Dendritic Cell Subsets and Development
Dendritic Cell Maturation
Antigen Processing and Presentation
Dendritic Cell-Mediated Immune Responses
Dendritic Cells in Disease
Dendritic Cells and Cancers
Immunotherapeutic Strategies and Clinical Trials
Future Directions
Suggested Readings
References
Chapter 21. Natural Killer Cell Immunity AND THERAPY
Abstract
Natural Killer Cell Fundamental Biology
Natural Killer Cell Development
Natural Killer Cell Receptors
Adaptive Immune Properties Of Natural Killer Cells
The Role Of Natural Killer Cells In Human Disease
The Therapeutic Potential Of Natural Killer Cells
Future Directions
Suggested Readings
References
Chapter 22. B-Cell Development
Abstract
Stages of B-Cell Development
B Lineage Specification and Commitment
Immunoglobulin Gene Rearrangement
The Pro-B- and Pre-B-Cell Checkpoints
The Hematopoietic Microenvironment
Fetal B-Cell Development
Secondary Lymphoid Tissues
Effects of Aging on B-Cell Development and Function
References
Chapter 23. Complement And Immunoglobulin Biology Leading To Clinical Translation
Abstract
The Complement System: An Overview
Immunoglobulins
Therapeutic Use Of Immunoglobulin
Drugs Targeting The Complement System
References
Suggested Readings
Chapter 24. T-Cell Immunity
Abstract
T-Cell Activation
T-Cell Development
T-Cell Function
Maturation Of T-Cell-Mediated Immunity
Inhibition Of T Cell-Mediated Immunity
Therapeutic Manipulation Of T-Cell-Mediated Immunity
Suggested Readings
References
Chapter 25. Unmodified Ex Vivo Expanded T Cells
Abstract
Adoptive Immunotherapy of Viral Infections with Virus-Specific T Cells
Adoptive Immunotherapy Of Cancer
Future Directions
Suggested Readings
References
Chapter 26. Treatment of Hematologic Malignancies With Genetically Modified T Cells
Abstract
Types of Cellular Immunotherapy
Genetic Modification of T Cells
Future Applications and Implementation of Cell Therapies for Cancer
Acknowledgment
References
Part IV: Disorders of Hematopoietic Cell Development
Chapter 27. Biology Of Erythropoiesis, Erythroid Differentiation, And Maturation
Abstract
Erythroid Cell Compartments
The Morphologically Recognizable Erythroid Precursor Cell Compartment
Intrinsic Control of Erythropoiesis
Cellular Dynamics in Erythropoiesis: Steady State and Stress Erythropoiesis
Ontogeny of Erythropoiesis
Suggested Readings
References
Chapter 28. Granulocytopoiesis and Monocytopoiesis
Abstract
Granulocytopoiesis
Control of Granulopoiesis
Role of Developmentally Important Neutrophil-Specific Genes In Disease
Eosinophil Production
Basophil and Mast Cell Production
Monocytopoiesis
Suggested Readings
References
Chapter 29. Thrombocytopoiesis
Abstract
Megakaryocyte Biology
Unique Features Of Megakaryocytes
Cytokine Regulation Of Thrombocytopoiesis
Transcriptional Control Of Megakaryocytopoiesis
Micro Rnas In Megakaryocytopoiesis
Future Directions
Suggested References
References
Chapter 30. Inherited Bone Marrow Failure Syndromes
Abstract
Introduction
Inherited Bone Marrow Failure Syndrome With Multi-Lineage Cytopenias
Inherited Bone Marrow Failure Syndromes Predominantly with Anemia
Inherited Bone Marrow Failure Syndromes with Predominantly Neutropenia
Inherited Bone Marrow Failure Syndromes With Predominantly Thrombocytopenia
Suggested Readings
Chapter 31. Aplastic Anemia
Abstract
History
Classification
Epidemiology
Etiology And Pathogenesis
Pathophysiologic Pathways Leading To Aplastic Anemia
Typical And Atypical Presentations
Clinical Associations
Laboratory Evaluation
Diagnosis Of Aplastic Anemia
Bone Marrow
Differential Diagnosis Of Pancytopenia
Treatment
Prognosis
Suggested Readings
References
Chapter 32. Paroxysmal Nocturnal Hemoglobinuria
Abstract
Introduction and History
Epidemiology And Classification
Clinical Manifestations
Pathophysiology
Diagnosis And Differential Diagnosis
Evaluation OF Newly Diagnosed Patients
Treatment
Suggested Readings
References
Chapter 33. Acquired Disorders of Red Cell, White Cell, and Platelet Production
Abstract
Etiology and Classification
Pathogenesis
Primary Pure Red Cell Aplasia
Secondary Forms of Pure Red Cell Aplasia
Laboratory Evaluation
Medical
Hematopoietic Stem Cell Transplantation
Secondary Forms of Neutropenias
Laboratory Evaluation
Nutritional Deficiencies
Suggested Readings
References
Part V: Red Blood Cells
Chapter 34. Pathobiology of the Human Erythrocyte and Its Hemoglobins
Abstract
Essential Features of Red Blood Cell Homeostasis
Major Features of the Red Blood Cell Membrane
Enzymes of Red Blood Cell Intermediary Metabolism
Red Blood Cell Senescence and Destruction
Hemoglobin Synthesis, Structure, and Function
Nosology of Hemoglobinopathies
Suggested Readings
Chapter 35. Approach to Anemia in the Adult and Child
Abstract
Overview of Erythropoiesis
Definition, PhysioloGic Consequences and Symptoms of Anemia
Mechanisms of Anemia
Comparison of Etiologies of Anemia in Adults and Children
Future Directions
References
Chapter 36. Iron Homeostasis and Its Disorders
Abstract
Regulation of Cellular and Systemic Iron Homeostasis
Use of Iron for Erythropoiesis
Recycling of Erythrocyte Iron by Macrophages
Liver Regulation of Systemic Iron Homeostasis and Iron Storage
Intestinal Iron Absorption
Future Directions
References
Chapter 37. Disorders of Iron Homeostasis: Iron Deficiency and Overload
Abstract
Iron Deficiency
Iron Overload
References
Cases From Real Life
References
Chapter 38. Anemia of Chronic Inflammation
Abstract
Clinical Overview of Anemia of Chronic Inflammation
Etiology and Pathophysiology of Anemia of Chronic Inflammation
Pathophysiology of Iron Sequestration
Conclusion
References
Chapter 39. Heme Biosynthesis and Its Disorders: Porphyrias and Sideroblastic Anemias
Abstract
Heme Biosynthesis
Porphyrias
Sideroblastic Anemias
Sideroblastic Anemia and Porphyrinuria Caused By Drugs
Presentations Associated with Sideroblastic Anemia or Porphyrinuria
References
Suggested Readings
Chapter 40. Megaloblastic Anemias
Abstract
Cobalamin
Folates
Intracellular One-Carbon Metabolism And Cobalamin–Folate Relationships
Morphologic Expression Of Megaloblastosis
Neurologic Dysfunction With Cobalamin Deficiency
Other Effects Of Cobalamin And Folate Deficiency
Spectrum Of Clinical Presentations With Cobalamin Deficiency
Biochemical Indicators Of Evolving Deficiency
Biochemical Evaluation Of Cobalamin And Folate Deficiencies
Pathogenesis Of Cobalamin Deficiency
Pathogenesis Of Folate Deficiency
Megaloblastic Anemia Not Caused By Folate Or Cobalamin Deficiency
Therapy
Routine Supplementation Of Cobalamin And Folate
Future Directions
Suggested Readings
References
Chapter 41. Thalassemia Syndromes
Abstract
Definitions And Nomenclature
Epidemiology
Pathophysiology: General Principles
BETA-Thalassemia Syndromes
ALPHA-Thalassemia Syndromes
Thalassemic Structural Variants
Extraordinarily Unstable Hemoglobins
References
Suggested Readings
Chapter 42. Pathobiology of Sickle Cell Disease
Abstract
Early Years of Sickle Cell Disease Research
Genetic Considerations
Abnormal Molecular Behaviors of Sickle Hemoglobin
Abnormalities of Sickle Red Blood Cells
Disease Pathogenesis
The Unique Systems Biology of Sickle Cell Anemia
Inflammation
References
Chapter 43. Clinical Aspects of Sickle Cell Disease
Abstract
Genetic Epidemiology of the Sickle Gene
Variant Sickle Cell Syndromes
Prevalence
Clinical Laboratory Features and Diagnosis
Clinical Presentation and Management
Suggested Readings
References
Chapter 44. Hemoglobin Variants Associated With Hemolytic Anemia, Altered Oxygen Affinity, and Methemoglobinemias
Abstract
Unstable Hemoglobins
Hemoglobins With Increased Oxygen Affinity
Hemoglobins with Decreased Oxygen Affinity
Suggested Readings
Chapter 45. Red Blood Cell Enzymopathies
Abstract
Metabolic Pathways
Enzymopathies Associated with Hemolytic Anemia
Other Enzymopathies of the Glutathione Pathway
Other Enzymopathies of the Glycolytic Pathway
Other Enzymopathies
Enzymopathies Associated with Erythrocytosis
Enzymopathies Associated with Methemoglobinemia
Suggested Readings
Chapter 46. Red Blood Cell Membrane Disorders
Abstract
Vertical and Horizontal Interactions of Membrane Proteins and Disorders of Red Blood Cell Shape
Differential Diagnosis
Therapy and Prognosis
Hereditary Elliptocytosis and Related Disorders
Red Blood Cell Membrane Disorders Manifested by Target Cell Formation
Red Cell Membrane Variants and Infectious Disease
Suggested Readings
Chapter 47. Autoimmune Hemolytic Anemia
Abstract
History
Epidemiology
Pathobiology
Etiology and Pathophysiology
Symptoms, Clinical Findings, and Risks
Laboratory Diagnosis of Autoimmune Hemolytic Anemia
Immunologic Phenomena Associated with Autoimmune Hemolytic Anemia
Differential Diagnosis
Treatment
Future Directions
Acknowledgments
Suggested Readings
References
Chapter 48. Extrinsic Nonimmune Hemolytic Anemias
Abstract
Fragmentation Hemolysis: Microangiopathy
Other Forms of Mechanical Damage to Red Blood Cells
Drug-Induced Oxidative Hemolysis
Miscellaneous, Poorly Characterized Causes of Extrinsic Hemolytic Anemias
References
Part VI: Non-Malignant Leukocytes
Chapter 49. Neutrophilic Leukocytosis, Neutropenia, Monocytosis, and Monocytopenia
Abstract
Neutrophilic Leukocytosis (Neutrophilia)
Neutropenia (and Agranulocytosis)
Monocytosis
Monocytopenia
References
Chapter 50. Lymphocytosis, Lymphocytopenia, Hypergammaglobulinemia, and Hypogammaglobulinemia
Abstract
Quantitative Disorders of Lymphocytes
Quantitative Disorders of Immunoglobulins
References
Chapter 51. Disorders of Phagocyte Function
Abstract
Approach to Diagnosis of Phagocyte Function Disorders
Disorders of the Respiratory Burst Pathway
Disorders of Phagocyte Adhesion and Chemotaxis
Defects in the Structure and Function of Lysosomal Granules
Miscellaneous Inherited and Acquired Disorders of Phagocyte Function
References
Chapter 52. Congenital Disorders of Lymphocyte Function
Abstract
Defects of Thymus Organogenesis
Severe Combined Immune Deficiency Due to Early Defects in T-Lymphocyte Development
Other Combined Immunodeficiencies
Combined Immunodeficiencies With Osseous Dysplasia
Other Combined Immunodeficiencies
Disorders With T-Cell-Mediated Immune Dysregulation
Defects of Cell-Mediated Cytotoxicity
Defects of B-Cell Development and Function
B-Cell–Intrinsic Defects of Class-Switch Recombination
Suggested Readings
References
Chapter 53. Pediatric and Adult Histiocytic Disorders
Abstract
Langerhans Cell Histiocytosis
Juvenile Xanthogranulomatous Disease
Erdheim-Chester Disease
Rosai-Dorfman-Destombes Disease (or Sinus Histiocytosis with Massive Lymphadenopathy)
Hemophagocytic Lymphohistiocytosis
Distinctive Clinical Contexts
Hemophagocytic Lymphohistiocytosis Associated with Malignancies
Hemophagocytic Lymphohistiocytosis in the Context of a Rheumatologic Disease (R-HLH)
Hemophagocytic Lymphohistiocytosis in the Context of Immune-Activating Therapies (Rx-HLH)
Hemophagocytic Lymphohistiocytosis in the Context of Immune Compromise (IC-HLH)
Suggested Readings
References
Chapter 54. Lysosomal Storage Diseases, Focusing On Gaucher Disease: Perspectives And Principles
Abstract
Lysosomal Storage Diseases
Lysosomal Protein Biosynthesis and Sorting
Genetics of Lysosomal Storage Diseases
Diagnosis of Lysosomal Storage Diseases
Screening Programs
Laboratory Diagnosis
Baseline and Sequential Assessment
Specific Treatment
Cellular Therapy, Including Gene Therapy
Small Molecule Therapy
General Aspects of Treatment
Hematologic Aspects of Individual Lysosomal Storage Disorders
Splenomegaly
Excessive Bruising/Bleeding
Thrombosis
Abnormal Morphologic Appearances: Bone Marrow and Peripheral Blood
Gaucher Disease
Genetics and Biochemistry
Epidemiology
Clinical Manifestations
Laboratory Findings
Imaging Findings
Differential Diagnosis
Substrate Reduction Therapy
Associated Diseases: Parkinson and Malignancies
Prognosis
New Therapeutic Modalities, Including Gene Therapy
Conclusions and Future Directions
References
Chapter 55. Epstein-Barr Virus and Associated Lymphoproliferative Conditions
Abstract
Biology of Epstein-Barr Virus
Primary Epstein-Barr Virus Infection
Latent Epstein-Barr Virus Infection
Immune Response to Epstein-Barr Virus
Epstein-Barr Virus Vaccine Development
Infectious Mononucleosis
Inherited Immunodeficiency Disorders and Predisposition to Epstein-Barr Virus–Associated Neoplasms
Other Inherited Immunodeficiency Disorders Associated with Epstein-Barr Virus Disease
Epstein-Barr Virus–Associated Hemophagocytic Lymphohistiocytosis
Acquired Immunodeficiency and Epstein-Barr Virus–Associated Neoplasms
Immunotherapy for Epstein-Barr Virus–Associated Neoplasms
Other Epstein-Barr Virus–Associated Diseases
Future Directions
Suggested Readings
References
Part VII: Hematologic Malignancies
Chapter 56. Progress in the Classification of Hematopoietic and Lymphoid Neoplasms: Clinical Implications
Abstract
Progress in the Diagnosis and Classification of Myeloid Neoplasms
Evolving Concepts in Classification of Lymphoid Neoplasms
Dendritic Cell and Histiocytic Neoplasms
References
Chapter 57. Conventional and Molecular Cytogenomic Basis of Hematologic Malignancies
Abstract
Methods
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Chronic B-Cell Lymphocytic Leukemia (Chapter 76)
Multiple Myeloma
Lymphoma
Hairy Cell Leukemia (Chapter 77)
Allogeneic Hematopoietic Stem Cell Transplantation
Future Directions
References
Chapter 58. Pharmacology and Molecular Mechanisms of Antineoplastic Agents for Hematologic Malignancies
Abstract
Tumor Cell Heterogeneity of Hematologic Malignancies
Development of Chemotherapeutic Agents
Traditional Cytotoxic Antineoplastic Agents Targeting the Cell Cycle and DNA
Pharmacology of Traditional Chemotherapeutic Agents
Pharmacology of Targeted Antineoplastic Agents
Drug Resistance to Chemotherapeutic Agents or Multidrug Resistance
Future Directions
SUGGESTED READINGS
Reference
Chapter 59. Pathobiology of Acute Myeloid Leukemia
Abstract
Phenotype of Acute Myeloid Leukemia
Etiology of Acute Myeloid Leukemia
Genetic and Epigenetic Alterations in Acute Myeloid Leukemia
Biology of Acute Myeloid Leukemia
Future Directions
Suggested Readings
Chapter 60. Clinical Manifestations and Treatment of Acute Myeloid Leukemia
Abstract
Epidemiology
Clinical and Laboratory Manifestations
Diagnosis and Classification
Prognosis
Therapeutic Considerations at Initial Presentation
Acute Promyelocytic Leukemia
Blastic Plasmacytoid Dendritic Cell Neoplasm (Chapter 64)
Extramedullary Acute Myeloid Leukemia
Future Directions
Suggested Readings
Chapter 61. Myelodysplastic Syndromes
Abstract
History
Classification
Epidemiology
Pathobiology
Germline Predisposition
Clinical Manifestations
Laboratory Manifestations
Differential Diagnosis
Prognosis
Treatment of Patients with Myelodysplastic Syndromes
Future Directions
Suggested Readings
References
Chapter 62. Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome in Adults
Abstract
Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia
Transplantation for Myelodysplastic Syndrome
Future Directions
References
Suggested Readings
Chapter 63. Acute Myeloid Leukemia in Children
Abstract
Epidemiology
Pathobiology
Conclusion
Suggested Reading
References
Chapter 64. Blastic Plasmacytoid Dendritic Cell Neoplasm
Abstract
Epidemiology
Pathobiology
Clinical Manifestations and Recommended Diagnostic Evaluation
Histopathology
Differential Diagnosis
Prognosis
Therapy
Future Directions
Suggested Readings
References
Chapter 65. Myelodysplastic Syndromes and Myeloproliferative Neoplasms in Children
Abstract
Myelodysplastic Syndromes
Myeloproliferative Neoplasms
Chronic Myeloid Leukemia
Other Myeloproliferative Neoplasms
Future Directions
Suggested Readings
References
Chapter 66. Pathobiology of Acute Lymphoblastic Leukemia
Abstract
Introduction
Lineage-Specific Features of Leukemic Lymphoblasts
Genetic Basis of Acute Lymphoblastic Leukemia
Germline Predisposition in Acute Lymphoblastic Leukemia
Chemotherapy Resistance Mechanisms and Novel Therapeutic Targets
Future Directions
Suggested Readings
Chapter 67. Clinical Manifestations and Treatment of Childhood Acute Lymphoblastic Leukemia
Abstract
Epidemiology
Pathobiology
Genomics of Acute Lymphoblastic Leukemia
Clinical Manifestations
Differential Diagnosis
Prognosis
Therapy, Including Stem Cell Transplantation
Acute Lymphoblastic Leukemia Relapse
Immunotherapeutic Options for Acute Lymphoblastic Leukemia
Supportive Care
Drug Interactions
Late Effects of Treatment
Future Directions
Update
Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia
Update
Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma
References
Chapter 68. Acute Lymphoblastic Leukemia in Adults
Abstract
Epidemiology
Etiology
Clinical Manifestations
Clinical and Laboratory Evaluation
Approach to Diagnosis
Morphology
Cytochemistry
Immunophenotype
Cytogenetics and Molecular Genetics
Differential Diagnosis
Prognosis
Minimal Residual Disease
Treatment of Acute Lymphoblastic Leukemia
Remission Induction
Postremission Therapy
Central Nervous System Disease: Prophylaxis and Treatment
Maintenance Therapy
Allogeneic Stem Cell Transplant In First Complete Remission
Therapy for Specific Disease Subsets
Burkitt Lymphoma/Leukemia
Adolescents and Young Adults With Acute Lymphoblastic Leukemia: The Intersection Between Pediatric And Adult Care
Differences in Treatment for B- Versus T-Cell Acute Lymphoblastic Leukemia
Older Adults With Acute Lymphoblastic Leukemia
Relapsed Acute Lymphoblastic Leukemia
Novel Therapies
Survivorship
Future Directions
Suggested Readings
Epidemiology, Classification, and Prognosis
References
Chapter 69. Chronic Myeloid Leukemia
Abstract
Introduction and Historical Perspective
Epidemiology
Molecular Biology
Cellular Biology
Transformation to Accelerated and Blast Phase
Molecular Basis of Tyrosine Kinase Inhibitor Resistance
Diagnosis and Initial Workup
Risk Stratification
Differential Diagnosis
Monitoring Response to Therapy
Therapy
Approach to the Newly Diagnosed Chronic Phase Patient
Approach to the Patient with Tyrosine Kinase Inhibitor Resistance
Treatment-Free Remission
Future Directions
Acknowledgments
Suggested Readings
References
Chapter 70. The Polycythemias
Abstract
Erythropoiesis
Erythropoietin, Oxygen Sensing, and Hypoxia-Inducible Factor
The Erythropoietin Receptor
The Renin–Angiotensin System and Hematopoiesis
Definition and Classification of Polycythemia
Relative Polycythemia
Absolute Polycythemias
Secondary Polycythemias
Polycythemia Vera
Clinical Manifestations
Laboratory Manifestations
Cytogenomic Abnormalities
Differential Diagnosis
Prognosis
Therapy
Future Directions
Update
Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera
Suggested Readings
References
Chapter 71. Essential Thrombocythemia
Abstract
Epidemiology
Pathobiology
Clinical Manifestations
Laboratory Manifestations
Differential Diagnosis
Prognosis
Therapy
Future Directions
References
Chapter 72. Primary Myelofibrosis and Chronic Neutrophilic Leukemia
Abstract
Phylogeny of the Nomenclature: Primary Myelofibrosis
Epidemiology
Pathobiology of Primary Myelofibrosis
Driver mutations
The role of epigenetic mutations in the molecular landscape of primary myelofibrosis
Extramedullary hematopoiesis in primary myelofibrosis
Bone marrow fibrosis in primary myelofibrosis
Clonal Evolution of Primary Myelofibrosis
Clinical Manifestations
Laboratory Manifestations
Differential Diagnosis
Prognosis
Evolution of Prognostic Models in Primary Myelofibrosis
Management of PRIMARY MYELOFIBROSIS
Treatment of the anemic patient
Treatment of spleen-related and systemic symptoms
Allogeneic hematopoietic stem cell transplantation
Investigational therapeutic options
Future Directions
Chronic Neutrophilic Leukemia
Molecular pathogenesis of chronic neutrophilic leukemia
Clonal evolution
Clinical and laboratory features of chronic neutrophilic leukemia
Diagnosis
Differential diagnosis
Prognosis
Management of chronic neutrophilic leukemia
Future directions
References
Chapter 73. Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes
Abstract
Epidemiology
Diagnostic Evaluation and Criteria
Pathogenesis and Molecular Characterization
Risk Stratification and Prognosis
Treatment Approaches
Future Directions
Conclusion
References
Chapter 74. Eosinophilia, Eosinophilic Neoplasms, and the Hypereosinophilic Syndromes
Abstract
Epidemiology
Morphology and Phenotype of Eosinophils
Origin, Differentiation, Recruitment, and Activation of Eosinophils
Monitoring of Eosinophil Numbers and Activity in Health and Disease
Etiology and Pathobiology of Hypereosinophilia
Definition and Classification of Hypereosinophilia and Hypereosinophilic Syndrome
Clinical Manifestations of Hypereosinophilic Syndrome in Various Organ Systems and Differential Diagnosis
Treatment Algorithm, Treatment Options, and Prognosis
Summary and Future Perspectives
References
Chapter 75. Mast Cells and Mastocytosis
Abstract
Origin and Development of Mast Cells
Mast Cell Activation and Function
Tools to Study Human Mast Cells
Epidemiology and Classification of Mastocytosis
Treatment
Future Directions
Suggested Readings
References
Chapter 76. Chronic Lymphocytic Leukemia
Epidemiology
Familial Chronic Lymphocytic Leukemia
Pathobiology
B-Cell Receptor Pathway and Its Role in Pathogenesis
Clinical Manifestations
Diagnosis and Laboratory Manifestations
Monoclonal B-Cell Lymphocytosis
Laboratory Manifestations
Prognosis
Treatment
Targeted Therapy
Bruton Tyrosine Kinase Inhibitors
Treatment of Patients With Relapsed Chronic Lymphocytic Leukemia
Special Clinical Scenarios in Chronic Lymphocytic Leukemia
Infections in Patients With Chronic Lymphocytic Leukemia
Autoimmune Complications of Chronic Lymphocytic Leukemia
SARS-COV-2 and Chronic Lymphocytic Leukemia
Future Directions
Update
Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia
Update
Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease
Suggested Readings
Chapter 77. Hairy Cell Leukemia
Abstract
Epidemiology
Etiology and Cell of Origin
Clinical Presentation and Diagnosis
Differential Diagnosis
Treatment
Future Directions
References
Chapter 78. The Pathologic Basis for the Classification of Non-Hodgkin and Hodgkin Lymphomas
Abstract
Introduction and Historical Background
Mature B-Cell Neoplasms
T-CELL and Natural Killer-Cell Lymphomas
Suggested Readings
References
Chapter 79. Origin of Hodgkin Lymphoma and Therapeutic Targets
Abstract
CHARACTERISTICS AND ORIGIN OF HODGKIN LYMPHOMA
Therapeutic Targets
Conclusions and Future Directions
References
Chapter 80. Hodgkin Lymphoma
Abstract
Epidemiology and Etiology Incidence and Age of Onset
Pathobiology of Hodgkin Lymphoma
Diagnosis and Staging
Clinical Features
Prognostic Factors, Risk Stratification, and Treatment Groups
Treatment of Early-Stage Hodgkin Lymphoma
Treatment of Advanced-Stage Hodgkin Lymphoma
Relapsed and Refractory Hodgkin Lymphoma
Special Considerations
Long-Term Complications of Treatment in Hodgkin Lymphoma
Suggested Readings
References
Chapter81. Origin of Non-Hodgkin Lymphoma and Therapeutic Targets
Abstract
Overview of B-Cell Lymphomas
Diffuse Large B-Cell Lymphoma
Gene Expression Profiles Define Diffuse Large B-Cell Lymphoma Subtypes
Burkitt Lymphoma
Follicular Lymphoma
Mantle Cell Lymphoma
Other Non-Hodgkin Lymphomas
Future Directions
Suggested Readings
Chapter 82. Clinical Manifestations, Staging, and Treatment of Follicular Lymphoma
Abstract
Epidemiology
Pathogenesis
Clinical Presentation
Diagnosis of Follicular Lymphoma
Staging
Natural History
Treatment of Follicular Lymphoma
When to Institute Therapy
Treatment Approaches
Treatment of Relapsed Follicular Lymphoma
Suggested Readings
References
Chapter 83. Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal)
Abstract
Initial Evaluation of Marginal Zone Lymphoma
Staging of Marginal Zone Lymphoma
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Type
Splenic Marginal Zone Lymphoma
Nodal Marginal Zone Lymphoma
Suggested Readings
References
Chapter 84. Diffuse Large B-Cell Lymphoma of the Central Nervous System
Epidemiology
Pathogenesis
Clinical Presentation
Neuroimaging
Neuroimaging and Differential Diagnosis Prior to Biopsy
Tissue Diagnosis
Cerebrospinal Fluid Assessment for Diagnosis
Ophthalmology Exam and Vitreoretinal Specimen Testing for Diagnosis
Histology Characterization
Biomarkers for Diagnosis
Staging
Frontline Therapy and Response Assessment
Induction Therapy
Consolidation
Primary Central Nervous System Lymphoma in Older Adults
Induction in Older Adults—Should it Be REDUCED?
AUTOLOGOUS Hematopoietic Stem Cell Transplantation in Older Adults as Consolidation Therapy
Maintenance Therapy—Emerging Concept
Treatment of Primary Vitreoretinal Lymphoma - A Subset of Primary Central Nervous System Lymphoma
Real-World Treatment Patterns and Outcomes—Data from Population-Based Studies
Primary Central Nervous System Lymphoma in the Immunocompromised Host
Post-Transplant Lymphoproliferative Disease–Related Primary Central Nervous System Lymphoma
Autoimmune Disease–Related Primary Central Nervous System Lymphoma
Experimental Therapeutics in Primary Central Nervous System Lymphoma
NGR-Human Tumor Necrosis Factor With R-CHOP
Front-line Treatment Challenges and Controversies
Prognostic and Predictive Markers
Additional Prognostic and Predictive Markers
Relapsed and Refractory Disease
Non-Chemotherapeutic Targets and Agents
Prevention of Cns Relapse for Aggressive Systemic Lymphomas and Controversies
Perspective and Future Directions
Acknowledgments
Suggested Readings
References
Chapter 85. High-Grade B-Cell Lymphomas
Abstract
Diffuse Large B-Cell Lymphoma
Primary Central Nervous System Lymphoma
Burkitt Lymphoma
Salvage Therapy
Future Directions
References
Chapter 86. Mantle Cell Lymphoma
Abstract
Epidemiology
Pathobiology
Clinical Manifestations
Laboratory Manifestations
Diagnosis
Therapy
Prognosis
Future Directions
References
Chapter 87. Virus-Associated Lymphoma
Abstract
Epstein-Barr Virus
Kaposi Sarcoma–Associated Herpesvirus
Human T-Lymphotropic Virus-1
Human Immunodeficiency Virus-Associated Lymphomas
Hepatitis C Virus
Future Directions
Suggested Readings
References
Chapter 88. Malignant Lymphomas in Childhood
Abstract
Non-Hodgkin Lymphoma
Hodgkin Lymphoma
Rare Subtypes of Lymphoma
Future Directions
Suggested Reading
References
Chapter 89. T-Cell Lymphomas
Abstract
Classification and Cell of Origin
Chronic T-Cell Leukemias
Cutaneous T-Cell Lymphomas
References
Suggested Readings
Chapter 90. Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma
Abstract
Monoclonal Gammopathy of Undetermined Significance
Variants of Monoclonal Gammopathy of Undetermined Significance
Smoldering Multiple Myeloma
Risk Stratification
Future Directions
References
Chapter 91. Multiple Myeloma
Abstract
Screening, Epidemiology, and Risk Factors
Pathogenesis
Clinical Implications of Clonal Heterogeneity and Evolution
Immune and Bone Marrow Microenvironment
Clinical Manifestations
Genomic Biomarkers
Differential Diagnosis
Indications for Treatment
Treatment of Newly Diagnosed Myeloma
Relapsed Disease
Future Directions
Update
Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
Update
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma
Update
Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma
Suggested Readings
References
Chapter 92. Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma
Abstract
Epidemiology
Pathogenesis
Mutation in MYD88
CXCR4 Whim Mutations
Impact of WM Genomics on Clinical Presentation
Marrow Microenvironment
Clinical Features
Morbidity Mediated by the Effects of Immunoglobulin M
Laboratory Findings
Marrow Findings
Immunologic Abnormalities
Serum Viscosity
Imaging
Lymph Node Biopsy
Treatment
Future Directions
Suggested Readings
References
Chapter 93. Immunoglobulin Light-Chain Amyloidosis (Primary Amyloidosis)
Abstract
Epidemiology
Pathobiology of the Disease
Clinical Manifestations
Laboratory Manifestations
Differential Diagnosis
Prognosis
Mayo Clinic Treatment Approach in Newly Diagnosed Amyloid Light-Chain Amyloidosis
Conclusions
Future Directions
References
Suggested Readings
Part VIII: Comprehensive Care of Patients with Hematologic Malignancies
Chapter 94. Key Considerations for Managing Infections in the Compromised Host
Abstract
Hematologic Conditions Predisposing To Infection
Infection Management In The Hematopoietic Stem Cell Transplant Recipient: A Model Of Severe Immune Deficiency
Suggested Readings
References
Chapter 95. Principles of Radiation Therapy for Hematologic Disease
Abstract
History and Background
Modern Radiation Planning and Treatment Techniques
Radiation Therapy by Diagnosis
Dose Constraints and Tolerances
Summary of Guidelines
Future Directions
Suggested Readings
References
Chapter 96. Grading and Toxicity Management after Immune Effector Therapy
Abstract
Cytokine Release Syndrome
Grading of Cytokine Release Syndrome
Management of Cytokine Release Syndrome
Immune Effector Cell–Associated Neurotoxicity Syndrome
Grading of Immune Effector Cell–Associated Neurotoxicity Syndrome
Management of Immune Effector Cell–Associated Neurotoxicity Syndrome
Other Toxicities from Immune Effector Therapy
Conclusions
References
Chapter 97. Identification and Management of Checkpoint Inhibition Toxicity
Abstract
Immunotherapy-Related Fatigue and Systemic Toxicities
Dermatologic/Mucosal Toxicity
Diarrhea/Colitis
Hepatitis
Pneumonitis
Endocrinopathies
Patients with Autoimmune Disease
Conclusions
References
Chapter 98. Psychosocial Aspects Of Hematologic Disorders
Abstract
Clinical Course of Hematologic Malignancies
Hematopoietic Stem Cell Transplantation
Factors that Influence Psychosocial Adjustment
Differentiating Psychiatric Complications from Expected Psychologic Response
Screening for Psychologic Distress
Screening for Positive Psychological Wellbeing
Management of Psychosocial Problems
Future Directions
Suggested Readings
References
Chapter 99. Pain Management and Antiemetic Therapy in Hematologic Disorders
Abstract
Taxonomy of Pain
Evaluation of the Pain Complaint
Therapy Directed at the Underlying Etiology
Nonpharmacologic Methods of Pain Management
Pharmacotherapy
Specific Clinical Problems
Pathophysiology of Nausea and Vomiting
Patient Assessment
Therapy
Conclusion
Acknowledgments
Suggested Readings
References
Chapter 100. Palliative Care
Abstract
Communication
Relief of Suffering
Management Concerns During the Last Days of Life
Hospice Programs
Bereavement
Conclusion and Future Directions
References
Chapter 101. Therapy-Related Late Effects of Hematologic Malignancies
Abstract
Cardiovascular Disease
Pulmonary Effects
Endocrinologic Effects
Musculoskeletal Effects
Cognitive Impairment
Other Toxicities
Potential Late Effects By Diagnosis
Providing Clinical Care to Survivors
Future Directions
Suggested Readings
References
Part IX: Transplantation and Other Cell-Based Therapies
Chapter 102. Practical Aspects of Hematopoietic Stem Cell Harvesting and Mobilization
Stem Cell Donor
Stem Cell Collection
Collection Peripheral Blood Stem Cells
Combination Regimen
Collection of Peripheral Blood Stem Cells by Apheresis
Hematopoietic Stem Cell Product Quality
References
Chapter 103. Graft Engineering and Cell Processing
Abstract
Regulatory Issues With Cell Processing
Professional Standards
Manipulation of Hematopoietic Stem Cell Transplantation Products
Evaluation of Manipulated Allogeneic Grafts
Cellular Therapy Products
Future Directions
References
Chapter 104. Principles of Cell-Based Genetic Therapies
Abstract
Hematologic Diseases, Cellular Targets, and the Basis for Genetic Therapies
Vector Systems
Experience in Hematologic Clinical Trials to Date
Chronic Granulomatous Disease
Insertional Mutagenesis
Recent Modifications of Vector Systems Based on Clinical Experience
Future Directions
Acknowledgments
Suggested Readings
References
Chapter 105. Indications, Outcomes, and Donor Selection for Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies in Adults
Abstract
Background
Patient Population
Conditioning Regimens
Graft Sources
Impact of Measurable Residual Disease
Prevention of Relapse after Allogeneic Transplantation
Long-Term Survival after Allogeneic Transplantation
Disease-Specific Indications for Allogeneic Transplantation
Suggested Readings
References
Chapter 106. Unrelated Donor Hematopoietic Cell Transplantation
Abstract
The Human Leukocyte Antigen and Killer-Cell Immunoglobulin-LIKE Receptor Genetic Systems
Human Leukocyte Antigen Typing Methods
Genetics of the Killer-CellImmunoglobulin-Like Receptors System
Killer-Cell Immunoglobulin-Like Receptors Typing Methods
Donor Identification and Likelihood of Transplantation
Human Leukocyte Antigen Criteria
Human Leukocyte Antigen Vector of Mismatching
Human Leukocyte Antigen Haplotypes
Donor Killer-Cell Immunoglobulin-LIKE Receptor Criteria
Clinical Significance of Human Leukocyte Antigen and Killer-Cell Immunoglobulin-LIKE Receptor in Transplantation
Summary
Suggested Readings
References
Chapter 107. Haploidentical Hematopoietic Stem Cell Transplantation
Abstract
Introduction
Historical Perspective
Immunological Considerations of Major Human Leukocyte Antigen Mismatched Grafts
Modern approaches to haploidentical transplantation (Fig. 107.3)
Comparative Outcomes Between Haploidentical and Other Donor Grafts
Potential Complications After Haploidentical Transplantation
Donor Selection for Haploidentical Transplantation (Table 107.4)
Conclusions and Future Directions
References
Suggested Readings
Chapter 108. Cord Blood Transplantation
Cord Blood as a Stem Cell Source
Cord Blood Unit Selection
Donor-Specific Antibodies
Conditioning Regimens in Cord Blood Transplantation
Graft-Versus-Host Disease in Cord Blood Transplantation
Outcomes of Cord Blood Transplantation
Other Diseases
Outcomes of Cord Blood Relative to Other Donor Types
Strategies to Improve Cord Blood Transplantation Outcomes
Supportive Care in Cord Blood Transplantation
Summary
Suggested Readings
References
Chapter 109. Graft-Versus-Host Disease and Graft-Versus-Leukemia Responses
Abstract
Graft-Versus-Host Disease: Clinical and Pathologic Aspects
Pathophysiology of Acute Graft-Versus-Host Disease
Biomarkers of Graft-Versus-Host Disease
Chronic Graft-Versus-Host Disease
Chronic Graft-Versus-Host Disease: Pathophysiology
Therapy for Chronic Graft-Versus-Host Disease
Syngeneic Graft-Versus-Host Disease
Graft-Versus-Leukemia Responses
Donor Leukocyte Infusions
Future Directions
Update
Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis
References
Chapter 110. Supportive Care for the Transplant Patient
Abstract
Infections
Early Non-Infectious Complications
Late Non-Infectious Complications
Graft-Versus-Host Disease
Future Directions
Suggested Readings
References
Part X: Transfusion Medicine
Chapter 111. Human Blood Group Antigens and Antibodies
Abstract
Erythrocyte Blood Group Antigens
References
Chapter 112. Principles of Red Blood Cell Transfusion
Abstract
Red Blood Cell Components
Appropriate Transfusion Practice in Various Clinical Settings
Red Blood Cell Preservation and Storage
Biochemical Changes Associated with Red Blood Cell Storage
Red Cell Alloimmunization
Alternatives to Allogeneic Red Cell Transfusions
Blood Substitutes
Red Blood Cell Substitutes
Suggested Reading
Chapter 113. Clinical Considerations in Platelet Transfusion Therapy
Abstract
Platelet Collection and Manufacturing
Prophylactic Platelet Transfusion
Adverse Effects of Platelet Transfusion
Platelet Refractoriness
References
Chapter 114. Human Leukocyte Antigen and Human Neutrophil Antigen Systems
The Genetics, Structure, and Function of Human Leukocyte Antigen Molecules
Organization of the Human Leukocyte Antigen Genes
Inheritance and Linkage Disequilibrium
Structure of the Human Leukocyte Antigen Class I and II
Expression of Human Leukocyte Antigen Molecules
Human Leukocyte Antigen Polymorphism and Its Clinical Significance
Nonclassic Major Histocompatibility Complex and Major Histocompatibility Complex Class I Chain-Related Molecules
Non-Human Leukocyte Antigen Polymorphism and Its Clinical Significance
Human Leukocyte Antigen Nomenclature
Immunologically Defined Human Leukocyte Antigen Nomenclature
Sequence-Defined Allelic Nomenclature
Human Leukocyte Antigen Typing in Clinical Hematology and Determination of Compatibility Human Leukocyte Antigen Typing
Testing for Allosensitization and Determination of Compatible Donor-RECIPIENT Pairs
The Human Leukocyte Antigen Molecules as Antigens and Human Leukocyte Antigen Alloimmunization
Human Leukocyte Antigen as a Functional Mediator of Graft-Versus-Host Disease and/or Graft-Versus-Neoplasia Effect
Graft-Versus-Host Disease
Graft-Versus-Neoplasia Effect
Human Leukocyte Antigen and T-Cell-Directed Immunization
Monitoring Immune Responses With Tetrameric Human Leukocyte Antigen-Peptide Complexes
Human Leukocyte Antigen Summary
Human Neutrophil Antigens and Their Clinical Significance
The HNA-1 Antigen System
The HNA-2 Antigen System
The HNA-3 Antigen System
HNA-4 and HNA-5 Antigen Systems
Clinical Significance of Antibodies to Neutrophil Antigens
Autoimmune Neutropenia of Childhood
Transfusion Reactions
Neutrophil Antigens Summary
Suggested Readings
References
Chapter 115. Principles Of Plasma And Plasma Derivatives
Abstract
Plasma
Cryoprecipitate
Plasma Derivatives
Albumin
Human Immunoglobulin
Hyperimmune Immunoglobulin Products
Coagulation Factor Concentrates
References
Suggested Readings
Chapter 116. Hemapheresis
Abstract
Principles of Apheresis
Technology and Techniques
Therapeutic Plasma Exchange (Plasmapheresis)
Replacement Fluids for Plasma Exchange
Mononuclear Cell Collection for Cellular Immunotherapies
Pediatric Hemapheresis
Complications of Therapeutic Apheresis
Conclusions and Future Directions
References
Chapter 117. Transfusion Reactions to Blood and Hematopoietic Stem Cell Therapy Products
Abstract
Hemolytic Transfusion Reactions
Acute Intravascular Hemolytic Transfusion Reactions
Acute Extravascular Hemolytic Transfusion Reactions
Delayed Hemolytic Reactions
Febrile Nonhemolytic Transfusion Reactions
Allergic Transfusion Reactions
Transfusion-Related Acute Lung Injury
Transfusion-Associated Circulatory Overload
Hypotensive Transfusion Reaction
References
Chapter 118. Transfusion-Transmitted Diseases
Abstract
Hepatitis Viruses
Retroviral Infections
Human Herpesvirus Infections
Epstein-Barr Virus (HHV-4)
Parvovirus
West Nile Virus
Dengue Viruses
Chikungunya Virus
Zika Virus
SARS-CoV-2 (COVID-19)
Pandemic Influenza A
Bacterial Infections
Spirochete Infections
Parasitic Infections
Transmissible Spongiform Encephalopathies
Future Directions
Suggested Readings
References
Chapter 119. Pediatric Transfusion Medicine
Abstract
Pediatric Blood Banking
Technical Considerations/Mechanical Devices
Transfusion Medicine: General Indications and Dosing
Transfusion Medicine: Indications in Unique Pediatric Populations
References
Chapter 120. Transfusion and Apheresis Support for Sickle Cell Disease Patients
Abstract
Hemodynamic Considerations
Clinical Considerations for Transfusion
Acute Anemia
Transfusion for Complications of Sickle Cell Disease
Apheresis Supported Red Cell Exchange
PREPARATIVE TRANSFUSION for Stem Cell Transplantation
Selection of Red Cell Components for Transfusion
Red Cell Antigen Matching
Complications of Transfusion Therapy
Iron Overload
References
Part XI: Hemostasis and Thrombosis
Chapter 121. Overview of Hemostasis and Thrombosis
Abstract
Introduction
Hemostatic System
Disorders of Hemostasis or Thrombosis
Treatment of Disorders of Hemostasis and Thrombosis
References
Chapter 122. Blood Vessels
Abstract
Hemostatic, Hematopoietic, and Vascular Systems as a Functional Continuum
Structure and Function of the Vessel Wall
Endothelial Structure, Function, and Heterogeneity
Physiologic Functions of the Endothelium
Interaction of Blood Cells with the Vessel Wall
Endothelial Cell Activation and Dysfunction
Molecular Regulators of Vascular Growth Responses
Pleiotropic Regulators of Vascular Growth
Endogenous Inhibitors of Vascular Growth
Cellular and Molecular Programs Involved in Blood Vessel Growth and Homeostasis
Mechanisms Triggering Blood Vessel Growth
Therapeutic Implications of Endothelial and Angiogenic Responses to Disease
Tumor Angiogenesis and Antiangiogenesis
Angiogenesis and Antiangiogenesis in Hematopoietic Malignancies
Hematologic Complications Associated With Blood Vessel-Directed Agents
Relationship Between the Vasculature and Hematopoiesis
Summary
Suggested Readings
References
Chapter 123. Megakaryocyte And Platelet Structure
Abstract
Megakaryocyte Development
Regulation of Megakaryocyte Development
Platelet Formation
Platelets
References
Chapter 124. Molecular Basis of Platelet Function
Abstract
Molecular Basis of Platelet Adhesion
Molecular Basis of Platelet Activation
Molecular Basis of Platelet Aggregation
Molecular Basis of Inherited Platelet Disorders
Suggested Readings
References
Chapter 125. Molecular Basis of Blood Coagulation
Abstract
Inventory: Procoagulant, Anticoagulant, and Fibrinolytic Proteins, Inhibitors and Receptors
Connectivity and Dynamics in Hemostasis
Summary
Acknowledgments
Suggested Readings
References
Chapter 126. Evaluation of the Patient With Suspected Bleeding Disorders
Abstract
BLEEDING HISTORY EVALUATION
Bleeding Score
The Physical Examination
Epidemiology and Genetics
Laboratory Manifestations
Prognosis
Therapy
Summary
Suggested Readings
References
Chapter 127. Laboratory Evaluation of Hemostatic and Thrombotic Disorders
Abstract
Laboratory Evaluation of Coagulation Proteins
Screening for Coagulation Protein Defects: Activated Partial Thromboplastin Time, Prothrombin Time, and Thrombin Clotting Time
Evaluation of Specific Coagulation Protein Defects
Practical Approach to Laboratory Testing of Coagulation Proteins
Laboratory Evaluation of Platelets and Von Willebrand Factor
Laboratory Evaluation of Fibrinolysis
Other Activities for Hemostasis Laboratories
References
Chapter 128. Acquired Disorders of Platelet Function
Abstract
Drugs, Foods, and Additives that Affect Platelet Function
Antiplatelet Drugs
Other Drugs that Adversely Affect Platelet Function
Clonal Disorders
Systemic Metabolic Disorders
Platelet Dysfunction Related with Extracorporeal Circuits
Infectious Diseases
Suggested Readings
References
Chapter 129. Diseases of Platelet Number: Immune Thrombocytopenia, Neonatal Alloimmune Thrombocytopenia, and Posttransfusion Purpura
Abstract
Immune Thrombocytopenia
Clinical Features
Fostamatinib
Immune Suppressant Medications
Neonatal Alloimmune Thrombocytopenia
Posttransfusion Purpura
Suggested Readings
References
Chapter 130. Thrombocytopenia Caused by Hypersplenism, Platelet Destruction, or Surgery/Hemodilution
Abstract
Approach to Patients with Thrombocytopenia
Anatomy and Physiology
Pathologic Platelet Sequestration: Hypersplenism
Drug-Induced Thrombocytopenic Syndromes
Drug-Induced Immune Thrombocytopenia
Drug-Induced Immune Thrombocytopenia of Rapid Onset
Thrombocytopenia Caused By Glycoprotein Iib/Iiia Receptor Antagonists
Hemodilution and Platelet Consumption After Surgery
Suggested Readings
References
Chapter 131. Heparin-Induced Thrombocytopenia
Abstract
Epidemiology
Pathobiology
Clinical and Laboratory Manifestations
Autoimmune Hit
Differential Diagnosis
Clinical Scoring Systems
Laboratory Diagnosis
Prognosis
Therapy
Platelet Count Monitoring for Heparin-Induced Thrombocytopenia
Anticoagulation and Previous Heparin-Induced Thrombocytopenia
Suggested Readings
References
Chapter 132. Thrombotic Thrombocytopenic Purpura and the Hemolytic Uremic Syndromes
Abstract
Differential Diagnosis
Treatment of Thrombotic Thrombocytopenic Purpura
Infection-Associated Hemolytic Uremic Syndrome
Atypical Hemolytic Uremic Syndrome
Genetics
Other Thrombotic Microangiopathic Disorders
Suggested Readings
References
Chapter 133. Structure, Biology, and Genetics of von Willebrand Factor
Abstract
Functions of Von Willebrand Factor
Basal Von Willebrand Factor Levels
Von Willebrand Factor Gene
Domain Structure
Biosynthesis
Storage and Secretion
ADAMTS13
Clearance
ABO Blood Groups
Areas of Ongoing Investigation
Von Willebrand Disease
Suggested Readings
References
Chapter 134. Hemophilia A and B
Abstract
Epidemiology
Factor VIII Biology: Genetics, Structure, Function, and Pathophysiology
Pathophysiology of Hemophilia A
Factor Ix Biology: Genetics, Structure, Function, and Pathophysiology
Clinical Features of Hemophilia
Clinical Management of Hemophilia
Inhibitors in Hemophilia B
Management of Inhibitors in Hemophilia B
Gene Therapy for Hemophilia
Hemophilia in the World—Economic Considerations
Acknowledgment
Update
Hematology: Basic Principles and Practice, 8e
Update
Hematology: Basic Principles and Practice, 8e
Suggested Readings
References
Chapter 135. Rare Coagulation Factor Deficiencies
Abstract
Inherited Fibrinogen Deficiency (OMIM 202400)
Inherited Dysfibrinogenemia (Omim 134820 Aa Chain, 134830 Bb Chain, 134850 g Chain)
Inherited Prothrombin Deficiency (Omim 176930)
Inherited Factor V Deficiency (Omim 227400)
Inherited Factor Vii Deficiency (Omim 227500)
Inherited Factor X Deficiency (OMIM 227600)
Inherited Factor Xi Deficiency (Omim 264900)
Deficiencies of Factor Xii, Prekallikrein or High Molecular Weight Kininogen
Inherited Factor Xiii Deficiency (Omim 134570 [A Subunit] and 134580 [B Subunit]
Inherited Deficiencies Involving Multiple Coagulation Factors
References
Chapter 136. Transfusion Therapy for Coagulation Factor Deficiencies
Abstract
Hemophilia A and B
Transfusion Therapy for Hemophilia A and B
Treatment of Hemophilia
Inhibitors of Factor VIII and Factor IX
Von Willebrand Disease
Acquired Factor VIII and Von Willebrand Factor Deficiency
Other Coagulation Protein Deficiencies
Other Plasma-Derived Protein Concentrates
Future Directions
Suggested Readings
References
Chapter 137. Disseminated Intravascular Coagulation
Abstract
Epidemiology
Pathobiology
Clinical Manifestations
Laboratory Manifestations
Differential Diagnosis
Therapy
References
Chapter 138. Hypercoagulable States
Abstract
Inherited Hypercoagulable States
Acquired Hypercoagulable States
Combined Inherited and Acquired Hypercoagulable States
Clinical Evaluation of Patients with Hypercoagulable States
Thrombophilia Screening
Laboratory Evaluation of Thrombophilia
Management of Thrombosis in Patients with Hypercoagulable States
Conclusions and Future Directions
References
Chapter 139. Antiphospholipid Syndrome
Abstract
Definition of Antiphospholipid Syndrome
Antigenic Specificities of Antiphospholipid Antibodies
Pathogenic Effects of Antiphospholipid Antibodies
Antiphospholipid Assays
Clinical Manifestations of the Antiphospholipid Syndrome
Criteria Manifestations of Antiphospholipid Syndrome
Reproductive Manifestations
Non-Criteria Manifestations of Antiphospholipid Syndrome
Hematological Abnormalities
Catastrophic Antiphospholipid Syndrome
Treatment of Antiphospholipid Syndrome
Other Treatments for Antiphospholipid Syndrome
Suggested Readings
Chapter 140. Venous Thromboembolism
Abstract
Epidemiology
Pathogenesis of Venous Thromboembolism
Clinical Manifestations of Venous Thromboembolism
Diagnosis of Venous Thromboembolism
Evaluation for Underlying Malignancy
Treatment of Venous Thromboembolism
Venous Thromboembolism Management in Specific Populations
Psychosocial Considerations
Prevention of Venous Thromboembolism
Attributions
Suggested Readings
References
Chapter 141. Prevention and Treatment of Venous Thromboembolism in Pregnancy
Abstract
Epidemiology
Pathophysiology
Clinical Manifestations
Differential Diagnosis
Laboratory Manifestations
Prognosis
Therapy
Covid-19 and Pregnancy
Future Directions
References
Chapter 142. Atherothrombosis
Abstract
Pathobiology
Central Role of Lipoproteins in Atherogenesis
Foam Cell Formation and the Fatty Streak
Lesion Evolution: Remodeling and the Vulnerable Plaque
Plaque Rupture and Acute Arterial Thrombosis
Hyperlipidemia, Atherosclerosis, and a Systemic Prothrombotic State
Cross Talk Between Coagulation and Inflammation Systems Impact Atherogenesis
Plaque Regression
Additional Future Directions
References
Chapter 143. Antithrombotic Drugs
Abstract
Antiplatelet Drugs
Anticoagulants
Oral Anticoagulants
Fibrinolytic Drugs
Conclusions and Future Directions
References
Chapter 144. Stroke
Abstract
Definition
Epidemiology
Pathobiology
Clinical Manifestations
Investigations
Therapy
Prognosis
Future Directions
LIST OF TRIAL ACRONYMS
Update
Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke
Suggested Readings
Chapter 145. Acute Coronary Syndromes
Abstract
Classification
Pathophysiology
Antithrombotic Management
Reperfusion Therapy For St-Segment Elevation Myocardial Infarction
Antiplatelet Therapy
Anticoagulant Therapy
Conclusions and Future Directions
Update
Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia
Suggested Readings
References
Chapter 146. Peripheral Artery Disease
Abstract
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Prognosis
Therapy
Future Directions
Suggested Readings
References
Chapter 147. Atrial Fibrillation
Abstract
Epidemiology
Clinical Manifestations
Diagnosis
Prevention of Stroke and Thromboembolism
Anticoagulant-Related Bleeding
Future Directions
Update
Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation
References
Chapter 148. Bleeding And Clotting Disorders In Pediatrics
Abstract
Developmental Hemostasis
Bleeding Disorders In Pediatrics
Clotting Disorders In Pediatrics
Suggested Readings
References
Part XII: Consultative Hematology
Chapter 149. Hematologic Changes in Pregnancy
Abstract
Anemia in Pregnancy
Hemoglobinopathies and Pregnancy
Other Hemolytic Anemias
Thrombocytopenia
Leukemia and Lymphoma
Bleeding Disorders
Hemophilia A AND B
Venous Thromboembolism
Prophylactic Anticoagulation During Pregnancy
Thrombophilias and Pregnancy
Future Directions
References
Chapter 150. Hematologic Manifestations of End-Organ Failure
Abstract
Hematologic Manifestations of Liver Disease
Red Blood Cell Abnormalities
White Blood Cell Abnormalities
Platelet Abnormalities
Coagulation and Liver Disease
Treatment of Liver Disease–Related Bleeding
Hypercoagulability and Thrombosis in Patients with Liver Disease
Hematologic Manifestations of Renal Disease
Anemia
Bleeding Risk
Thrombosis
Thrombotic Microangiopathies
Hematologic Manifestations of Other End-Organ Diseases
Respiratory Disease
Heart Failure
Endocrinopathies
References
Suggested Readings
Chapter 151. Hematologic Manifestations of Solid Tumors
Abstract
Erythrocytes
Platelets
Leukocytes
Thrombosis and Cancer
Future Directions
Suggested Readings
References
Chapter 152. Hematologic Manifestations of HIV/AIDS
Abstract
Introduction to Human Immunodeficiency Virus
Summary
Suggested Readings
References
Chapter 153. Hematologic Findings And Consequences Of Novel Coronavirus (SARS-COV-2) Infection
Abstract
Thrombosis in Covid-19
Covid-19 Associated Coagulopathy
Inflammatory Markers and Cytokine Storm
Characteristics of the Complete Blood Count and White Blood Cell Differential in Covid-19
Vaccination
Monoclonal Antibodies
References
Chapter 154. Hematologic Aspects of Parasitic Diseases
Abstract
Malaria
Visceral Leishmaniasis
African Trypanosomiasis
American Trypanosomiasis
Babesiosis
Eosinophilia
Other Parasitic Diseases
Future Directions
Suggested Readings
References
Chapter 155. Hematologic Problems in the Surgical Patient: Bleeding and Thrombosis
Abstract
preoperative evaluation of hemostatic risk
Hemostatic Agents
Management of Patients With Hemostatic Abnormalities
Intraoperative and Postoperative Bleeding
Perioperative Anticoagulation Management
Summary
Suggested Readings
References
Chapter 156. The Spleen and Its Disorders
Abstract
Normal Splenic Anatomy And Function
Examination Of The Spleen
Imaging Of The Spleen
Tests Of Splenic Function
Asplenia And Hyposplenia
Acquired Hyposplenism
Splenomegaly And Hypersplenism
Splenic Irradiation
Splenectomy
Conclusions And Future Directions
References
Chapter 157. Aging and Hematologic Disorders
Abstract
Anemia
General Principles in Older Adults with Hematologic Malignancies
Lymphoma in Older Adults
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Multiple Myeloma in Older Adults
Hematopoietic Stem Cell Transplantation and Cellular Therapy in Older Adults
Conclusion
Acknowledgments
Suggested Readings
References
Chapter 158. Onco-Cardiology: Focus on Cardiac Complications of Hematologic Treatments
Abstract
Cardiotoxicity From Chemotherapy Used In Hematological Malignancies (Table 158.1)
Cardiotoxicity From Immunotherapy Used In Hematological Malignancies
Cardiotoxicity of Radiation Treatment
Cardiac Considerations During Hematopoietic Stem Cell Transplantation
Conclusion
References
Suggested Readings
Chapter 159. Resources for the Hematologist: Interpretive Comments and Selected Reference Values for Neonatal, Pediatric, and Adult Populations
Abstract
Appendix Contents
Index
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Edward J. Benz

Leslie E. Silberstein

Helen Heslop

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