Contents
About the Series Editor
About the Volume Editors
Contributors
Part I: Introduction
1 History of Bone Marrow Transplantation
Introduction
Bone Marrow Transplants: A Novel Treatment
The Era of Reduced Intensity Conditioned (RIC) Allogeneic Transplantation
The History of Graft Versus Tumor Effect and Graft Versus Host Disease
Reduced Intensity Conditioning
Comparing HSCT After Myeloablative and Nonmyeloablative Conditioning
The History of Unrelated Donor Transplants-Donor Registries
History of Haploidentical and Cord Blood Bone Marrow Transplants
The First Cord Blood Transplant
Cord Blood Bank Development
Establishing Quality an Standards in Bone Marrow Transplant Practice
Conclusion
References
Part II: Biology of Bone Marrow Transplantation
2 Stem Cell Biology in Bone Marrow Transplantation
Introduction
The Hierarchy of Hematopoiesis
The Hematopoietic Stem Cell Niche
General Information About the Hematopoietic Niche
Cytokines in the Hematopoietic Niche
Hematopoietic Niche Cells
Hematopoiesis in Aging
Conclusions
Cross-References
References
3 HLA in Hematopoietic Stem Cell Transplantation
Introduction
Nomenclature of HLA Alleles
A Brief History on the Discovery of HLA
Evolution of HLA Typing Methodologies from Serology to High-Throughput Ultra Deep Next Generation Sequencing
HLA Typing by RFLP (Restriction Fragment Length Polymorphism)
HLA Typing by SSP (Sequence-Specific Primers)
HLA Typing by SSO (Sequence-Specific Oligonucleotide Probes)
HLA Typing by Sanger Sequencing
HLA Typing by Next Generation Sequencing (NGS)
What Is Meant by HLA Matching?
HLA Matching in Hematopoietic Stem Cell Transplantation
Role of Donor-Specific HLA Antibodies in Partially Matched and Haploidentical HSCT
Role of Killer Cell Immunoglobulin Receptor (KIR) in HSCT
Conclusion
References
4 Biology of Graft-Versus-Host Disease
Introduction
Acute Graft-Versus-Host Disease
Transplant Conditioning and the Priming of the Immune Response
T-Cell Proliferation and Differentiation
Effector Phase of Graft-Versus-Host Disease
Chronic Graft-Versus-Host Disease
Clinical Manifestations of Chronic Graft-Versus-Host Disease
Phase 1 - Early Post-Transplant Inflammation and Tissue Injury on cGvHD
Innate and Adaptive Immune Responses to Chronic GvHD
Endothelial Damage and Activation
Effector T Cells
Phase 2 - Chronic Inflammation and Dysregulated Immunity
Thymic Dysfunction Leading to Chronic GvHD
Regulatory T Cells and Chronic GvHD
B-Cell Regulation and Chronic GvHD
Phase 3 - Fibrosis and Evolution of Chronic GvHD
Specific Subtypes of Chronic Graft-Versus-Host Disease
Effects of cGvHD on the Lung
Cutaneous cGvHD
Novel Factors Influencing the Development of Graft-Versus-Host Disease
Micronutrients in Graft-Versus-Host Disease
Vitamin A
Vitamin D
The Role of the Microbiome in the Development of Graft-Versus-Host Disease
The Role of MicroRNAs During Graft-Versus-Host Disease
Conclusion
References
5 Chimerism in Hematopoietic Stem Cell Transplantation
Introduction
Chimerism Analysis and Frequency of Monitoring
Genetic Information Used in Monitoring Host Hematopoiesis
STRs, VNTR, and Informativeness
SNPs and Insertion Deletion Polymorphisms (IDP)
Assay Design and Selection
Preanalytical Consideration
Pretransplant Sample Collection
Posttransplant Sample Collection
Available Technologies and Platforms
STR Genotyping
Split Chimerism
Calculations
Calculations of Single Donor
Calculations in Multiple Donors
PCR Effects and Variations
Stutter Peaks
Unbalanced Amplification:
Double Peaks
Capillary Electrophoresis Parameters
Error Assessment in STR Genotyping
Algorithm to Approach These Parameters (CV, LE, ME)
Quality Control Parameters
Other Platforms
FISH
RQPCR
Haplotype Counting
Next Generation Sequencing (NGS)
AlloHSCT and Chimerism Monitoring: Clinical Aspects
Schedule of Chimerism Assessment Post AlloHSCT
Chimerism in Nonmalignant Diseases
Hemoglobinopathies
Chimerism in Malignant Diseases
Conclusion
Cross-References
References
6 HSCT in Malignancies
Introduction
Changes in Indications and Patient Selection for HCT
Status of Transplants in Specific Diseases
Acute Myeloid Leukemia (AML)
Acute Lymphoblastic Leukemia (ALL)
Myelodysplastic Syndromes (MDS)
Chronic Myeloid Leukemia (CML)
Myeloproliferative Disorders Other than CML
Chronic Lymphocytic Leukemia (CLL)
Lymphomas
Diffuse Large B-Cell Lymphoma (DLBCL)
Follicular Lymphoma (FL)
Mantle Cell Lymphoma (MCL)
Hodgkin Lymphoma (HL)
T-Cell Lymphomas (PTCL)
Multiple Myeloma (MM)
Amyloidosis (AL)
Solid Tumors
References
7 HSCT in Benign Hematological Disorders
Introduction
Hemoglobinopathies
HSCT for Thalassemia Major
Matched Related Donor HSCT in Thalassemia Major
Newer Approaches for MRD HSCT in High-Risk Thalassemia
Other Graft Sources for MRD HSCT in Thalassemia Major
Related Cord Blood
PBSC
Alternative Donor HSCT in Thalassemia Major
Matched Unrelated Donors (MUD)
Haploidentical Donors
Unrelated Umbilical Cord Blood Donors in Hemoglobinopathies
Role of HSCT in Thalassemia Intermedia
Mixed Chimerism in Hemoglobinopathies
HSCT for Sickle Cell Disease
Patient Selection
Matched Related Donor HSCT in Sickle Cell Disease
Increased risk of neurologic events
Stabilization of Disease
Pain Crises
Cerebral Vasculopathy
Pulmonary
Health-Related Quality of Life (HRQoL)
Spleen
Gonads
Reduced Toxicity Regimens
Busulfan
Melphalan
Treosulfan
Low-dose TBI/Alemtuzumab Minimal Toxicity Nonmyeloablative Regimen
Alternative Donor HSCT in Sickle Cell Disease
Matched Unrelated Donors (MUD)
Haploidentical Donors
CD34+ Selection
CD3+ or TCR Ξ±Ξ²+ Depletion
Posttransplant Cyclophosphamide (PTCy)
Primary Immunodeficiency Disorders (PID)
HSCT for PID: General Considerations
HSCT for SCID/CID
HSCT for Primary Immune Regulatory Disorders
HSCT for Hemophagocytic Lymphohistiocytosis (HLH)
HSCT for WAS/ XLT
HSCT for Phagocytic Defects
Chronic Granulomatous Disease (CGD)
Leucocyte Adhesion Deficiency
Conclusion
Cross-References
References
8 Hemopoietic Stem Cell Transplant for Non-hematological Disorders
Introduction
General Considerations About HCT in IEM
HCT in Lysosomal Storage Diseases
Transplant in MPSIH, Hurler Syndrome
Transplant in Non-Hurler MPS
Transplant in Other, Non-MPS, Lysosomal Storage Disorders (LSD)
Krabbe Disease, Globiod Cell Leukodystrophy, Galactocerebrosidase Deficiency
Gaucher Syndrome, Glucocerebrosidase Deficiency
Wolman, Acid Lipase Deficiency
Metachromatic Leukodystrophy, Aryl Sulfatase Deficiency
Alpha-Mannosidosis, Alpha Mannosidase Deficiency
Other LSD
Stem Cell Gene Therapy in LSD
Transplant in X-Adreno-Leukodystrophy (X-ALD)
Cerebral Inflammatory Disease
Diagnosis
Monitoring
Hematopoietic Stem Cell Transplantation (HSCT) in Early Cerebral X-Adrenoleukodystrophy:
Transplant Techniques in X-ALD
Ex Vivo Stem Cell Gene Therapy in X-ALD
Transplant in MNGIE, and Other Mitochondrial Disease
Transplant in Malignant Infantile Osteopetrosis (MIOP)
Key Messages
The Central Role of the Osteoclast in MIOP
Clinical Features
Genetics of MIOP
Diagnostic Investigations in MIOP, and Relevance to HSCT
Specific Transplant Considerations in MIOP
Conclusion
Cross-References
References
Part III: Bone Marrow Transplantation: The Procedure
11 Unrelated Donor Allogeneic Transplant
Introduction
Logistics of URD Donor Selection
Outcomes After Allogeneic HCT Using URD Are Comparable to MRD
Impact of HLA-Mismatch on Transplant Outcomes
GVHD Prophylaxis Can Modulate URD Transplant Outcomes
Posttransplant Cyclophosphamide Reduces GVHD Among All Donor Types
Novel Approach to HLA Typing Using Next-Generation Sequencing
Donor-Specific HLA Antibodies
HLA-DP Haplotype
Non-HLA Determinants of Outcomes: KIR Gene Haplotype
Non-HLA Factors: Patient and Donor Clinical Characteristics
Graft Source in Unrelated Donor HCT
Impact of Age: Older Matched Sibling Donor Versus Younger Matched Unrelated Donor
Conclusion
Criteria for the Selection of Unrelated Donors
Cross-References
References
12 Umbilical Cord Blood Transplantation
Introduction
Milestones in Cord Blood Transplantation
Special Features of Cord Blood Stem Cells
Patient Selection for Cord Blood Transplantation
Cord Blood Transplantation in Children
Cord Blood Transplantation in Adults
Selection of Cord Unit
Key Points in Optimal Cord Unit Selection
The Impact of Conditioning Regimens
Supportive Care in Cord Blood Transplantation
Immune Reconstitution After Cord Blood Transplantation
New Technology and the Use of Cord Blood Stem Cells
Cord Versus Haploidentical Transplantation
The World of Regenerative Medicine
Public Versus Private Banking
Balancing the Cost of Care
Experience in Low- and Middle-Income Countries
Conclusion
Cross-References
References
13 Autologous Bone Marrow Transplant
Introduction
Stem Cells Mobilization
Preparatory (Conditioning) Regimen
Complications
Infections
Mucositis
Sinusoidal Obstruction Syndrome (SOS)
Diagnostic Criteria
Renal Dysfunction
Clinical Results
Acute Myeloblastic Leukemia (AML)
HodgkinΒ΄s Lymphoma (HL)
Non-Hodgkin Lymphoma
Mantle Cell Lymphoma
T-Cell Lymphomas
Follicular Lymphoma (FL)
Long-Term Efficacy
Maintenance After ASCT
Multiple Myeloma
Germ Cell Tumors of the Testis
Pediatric Solid Tumors
Stem Cell Transplantation in India
Conclusion
References
14 Transplant Pharmacology and Conditioning Therapy
Introduction
Defining Intensity of Conditioning
Myeloablative Conditioning
Total Body Irradiation-Based Myeloablative Regimens
High-Dose Chemotherapy Regimens
High-Dose Chemoradiotherapy Versus High-Dose Chemotherapy Regimens
Non-Myeloablative and Reduced Intensity Conditioning
Donor Engraftment and Chimerism Kinetics
GVHD Kinetics
Chemotherapeutic Agents and Drugs in Conditioning
Busulfan
Busulfan Pharmacokinetics and Systemic Exposure
Combinations with IV Bu
Cyclophosphamide
Fludarabine
Melphalan
Treosulfan
Radio Immunotherapy-Based Regimens
Anti-T-cell Antibody-Containing Regimens
Comparing Conditioning Intensity
Autologous Transplants
Conditioning Regimens for Multiple Myeloma
Conditioning Regimens in Lymphoma
Toxicity of Conditioning/Regimen-Related Toxicity
Choice of Conditioning Regimen
Conclusion
Cross-References
References
15 Total Body Irradiation in Stem Cell Transplant
Hematopoietic Stem Cell Transplantation: Background
Total Body Irradiation: Biological and Physical Principles
Radiobiology of Total Body Irradiation
Physics of Total Body Irradiation
Basic Principles
Techniques
Prescription and Dose Rate
Shielding and Boosting of Selected Organs During TBI
Quality Assurance and In Vivo Dosimetry
Toxicity of TBI
Acute Toxicity
Late Toxicity
Second Primary Neoplasms
Conclusion
Cross-References
References
16 Graft Versus Host Disease: Management of Acute and Chronic Disease
Introduction
Pathophysiology of Acute and Chronic Graft Versus Host Disease
Current Models for Acute and Chronic Graft Versus Host Disease
Characterization of the T-Cell Repertoire
Epidemiology, Clinical Manifestation, Diagnosis, and Staging
Acute Graft Versus Host Disease
Epidemiology
Clinical Manifestations and Diagnosis
Staging
Chronic Graft Versus Host Disease
Epidemiology
Clinical Manifestations and Diagnosis
Staging
Risk Factors for Graft Versus Host Disease
Major Histocompatibility Mismatch
Minor Histocompatibility Antigens
Conditioning Protocol
Graft Source and Manipulation
Other Clinical Factors
Risk Factors for Chronic Graft Versus Host Disease
Prophylaxis of Graft Versus Host Disease
Methotrexate and Calcineurin Inhibitors
Mycophenolate Mofetil
Sirolimus
Posttransplant Cyclophosphamide (CY)
T-Cell Depletion
Graft Engineering
Other Strategies
Treatment for Graft Versus Host Disease
Acute Graft Versus Host Disease: First-Line Treatment with Corticosteroids
Acute Graft Versus Host Disease: Treatment of Steroid-Resistant GVHD
Chronic Graft Versus Host Disease: First-Line Systemic Treatment
Chronic Graft Versus Host Disease: If Steroids Are Insufficient
Biomarkers and Prognostication
Conclusions
Cross-References
References
17 Immunosuppressive Therapy and Immunomodulation in Stem Cell Transplantation
Introduction
Immunosuppression and Immunomodulation During Stem Cell Transplantation
Non-specific Immunosuppressive Drugs
Corticosteroids
Methotrexate
Post-transplant High-Dose Cyclophosphamide
Mechanism of Action
Toxicities and Clinical Use
Specific T Cell Immunosuppressive Drugs
Cyclosporine
Tacrolimus
Sirolimus
Mycophenolate
Antibodies
Antithymocyte Globulin
Rituximab
Newer Agents
Ruxolitinib
Anti-cytokines
Ibrutinib
Induction of Anergy
Other Approaches
Summary
References
18 Hematopoietic Stem Cell Donor and Recipient Evaluation
Introduction
Medical History
Psychosocial Evaluation
Physical Examination
Laboratory Investigations
Adverse Donor Reactions
Counseling and Consent
Donor Deferral
Donor Follow-Up
Documentation
Issues Related to Pediatric Donor
Regulatory Issues
Special Considerations in Autologous HSC Donations
Hematopoietic Stem Cell Transplant Recipient Evaluation
Physiologic/Organ Evaluation
Pulmonary Evaluation
Cardiac Evaluation
Hepatic Evaluation
Renal Evaluation
Infectious Disease Evaluation
Dental Evaluation
Disease Assessment
Psychosocial Assessment
Hematopoietic Cell Transplantation (HCT)-Specific Comorbidity Index
Patient Education
Team Members
Registered Nurse Practice Implications
Conclusion
References
19 Setting up a Hematopoietic Stem Cell Transplantation Unit
Introduction
Defining
Planning
Physical Planning and Design Team
HSCT Project Team
Layout and Design
Designing Principle and Minimum Requirements
Civil Work
Zoning
Outer Zone
Intermediate Zone
Restricted Zone
Inner Aseptic Zone
Drug Reconstitution and Drug Storage Room
Clean Utility Room
Equipment Room/Charging Room
Duty Room
Patient Rooms
Corridor
Work Station
Dirty Zone
Fire Protection System
HVAC - Heating, Ventilation, and Air Conditioning
Personnel Planning
Functional Planning
Equipment Planning for Direct Patient Care
Financial Planning
Preventive Planning
HSCT Unit Infection Control
Microbiological Surveillance
Equipment Maintenance
Annual Maintenance
Donor Registry Interactions
Data Collection and Collaboration with Registries
Ancillary Services
Outpatient Services
Quality Management (QM)
Patient Care
Legal Requirements
Accreditation
Participation in Clinical Trials
Conclusion
References
9 Allogeneic Transplant Overview and Matched Related Donor Transplant
Introduction
Rationale for Allogeneic Transplantation
Indications for Allogeneic Transplantation
Overview of Allogeneic Transplant Procedure
Donor Search and Graft Source
Transplant Workup
Conditioning Regimen
Early Post-Transplant Supportive Care Phase
Long-Term Follow-Up Phase
Allogeneic Transplantation Outcomes
Prognostic Factors for Allogeneic HCT Outcomes
Treatment-Related Mortality
Survival After Allogeneic Transplantation
Graft-Versus-Host Disease
Early Complications After Allogeneic Transplantation
Graft Failure
Early Infections
Hepatic Veno-Occlusive Disease
Idiopathic Pneumonia Syndrome
Late Complications After Allogeneic Transplantation
Late Infections
Secondary Malignancies
Organ-Specific Late Complications
Matched Related Donor Transplantation
Conclusion
Cross-References
References
10 Haploidentical Transplantation: Challenges and Solutions
Introduction
Biological Basis for HFD-HCT
Development of HFD-HCT Through Shifting Paradigms
Graft Manipulation
Unmanipulated Graft with Pharmacological Interventions
High-Dose Posttransplantation Cyclophosphamide (PTCy)
G-CSF Primed Marrow Graft and Intensive Pharmacological GVHD Prophylaxis: The Beijing Protocol
NK Cell Immunology in the Context of HFD-HCT
Approach to HFD-HCT for Hematological Malignancies
Conditioning Regimens
Acute Leukemia
Lymphoma
Graft Source: Mobilized PB or BM, or Both
Treatment and Prevention of Relapse Following HFD-HCT
Donor Lymphocyte Infusion (DLI) and T-Cell-Based Immunotherapy
NK Cell-Based Approaches
Cytokine-Induced Killer (CIK) Cells
Infusion of Tregs Followed by Effector T Cells
T-Cell Costimulation Blockade (COSBL) for Tolerance Induction
CTLA4Ig-Primed DLI: Possible Dissociation of T-Cell Alloreactivity and NK Cell GVL
Comparison of HFD-HCT with Other Donor Sources
Considerations for HFD-HCT in Nonmalignant Disorders
Acquired SAA (aqSAA)
Hemoglobinopathies
Posttransplantation Hemophagocytic Syndrome (PTHPS)
Choice of Donor and the Graft
Donor-Specific Anti-HLA Antibodies (DSA)
Donor Age
Donor Gender and Mother as Donor
Do Family Relationships Have Any Role in Outcome
ABO Compatibility
Impact of Mismatches in the HLA Incompatible Haplotype
NK Cell Profile
Recommendations Regarding HFD
Immunobiology of a Haploidentical Graft
Conclusion
Cross-References
References
Part IV: Stem Cell Processing
20 Hematopoietic Stem Cell Collection Techniques
Introduction
PBSC Harvesting
Timing of PBSC Collection
Allogeneic PBSC Collection
Autologous PBSC Collections
Vascular Access
Illustration
Anticoagulation
Apheresis Procedure Specifications
Patient and Donor Care During Apheresis Procedures
Analysis of Collected Product and Quality Control
Cell Count and Differential
Sterility Check
Assessment of Cell Viability
Medical Evaluation
Complications of PBSC Collection
Cell Separators
Records and Labelling
Bone Marrow Collection Techniques
Cord Blood Collection
Pediatric Bone Marrow and PBSC Collection
Conclusion
References
21 Ex Vivo Manipulation of Stem Cell Product
Introduction
Methods of Ex Vivo Graft Manipulation
Minimal Manipulation
RBC and Plasma Depletion
Volume Reduction
Washing to Reduce Plasma Antibodies or Anticoagulants
Extensive Manipulations
Preclinical Models of TCD
Ex Vivo TCD Methods
Physical Separation Techniques
Immunological Techniques
Combined Immunological/Physical Methods
Ex Vivo Graft Manipulation Strategies
The Megadose Concept and CD34+ PositiveSelection
Pan T-Cell Depletion
CD8+ T-Cell Depletion
CD3/CD19 Cell Depletion
Ξ±Ξ² T-Cell/CD19 Cell Depletion
Add Back Adoptive Immunity and Donor Lymphocyte Infusion (DLI)
Advantages of TCD
GvHD Prevention
Organ Dysfunction after TCD BMT
Transplant-Related Mortality
Limitations Associated with TCD
Graft Failure
Prolonged Immunodeficiency
EBV-LPDs
Leukemia Relapse
Conclusion
Cross-References
References
22 Cryopreservation of Stem Cell Product
Introduction
Historical Background
Steps of a Cryopreservation Protocol
Types of Cryoprotectants, Cryopreservation Solution, and Cryoinjury
Freezing Rate and Freezing Curve
Storage of Cryopreserved Cells
Thawing of Frozen HSPC Grafts and Adverse Reactions
Conclusion
Cross-References
References
Part V: Supportive Care in Bone Marrow Transplantation
23 Acute Complications in Stem Cell Transplantation
Introduction
Acute Complications Post HSCT
Endothelial Complications
Engraftment Syndrome (ES)
Definition and Synonyms
Pathogenesis
Incidence and Risk Factors
Clinical Features
Biomarkers
Management
Capillary Leak Syndrome (CLS)
Incidence and Risk Factors
Diagnostic Criteria
Treatment
Transplant Associated Thrombotic Microangiopathy (TA-TMA)
Introduction
TMA
Incidence
Pathogenesis and Risk Factors
Diagnosis
Treatment
Prognosis
VOD (Veno-Occlusive Disease)/SOS (Sinusoidal Obstruction Syndrome)
Introduction
Risk Factors
Diagnosis
EBMT Revised Criteria for VOD (Both Adults and Children)
Grading of Severity
McDonald Grading System of SOS/VOD
Prophylaxis and Treatment
Recommended
Treatment
Supportive Care
Defibrotide
Methylprednisolone
t-PA (Tissue Plasminogen Activator)
Liver Transplantation and TIPS (Transjugular Intrahepatic Portosystemic Shunt)
Prognosis
Novel Trends
Noninfectious Pulmonary Syndromes
Posttransplant Noninfectious Pulmonary Complications
Idiopathic Pneumonia Syndrome (IPS)
Definition
Incidence and Risk Factors
Risk Factors for IPS
Clinical Presentation
Prognosis
Pathogenesis
Management
Definitive Therapy
Novel Trends
Risk Factors
Clinical Presentation
Treatment
Prognosis
PRES (Posterior Reversible Encephalopathy Syndrome)
Management
Prognosis
Graft Failure
DSA (Donor-Specific Antibodies)
Management of DSA Positive Recipients
Management of Graft Failure
Prevention
Treatment
Mucositis
Management
Recent Trends in Mucositis
Conclusion
Cross-References
References
24 Infections in Hematopoietic Stem Cell Transplantation (HSCT) Patients
Introduction
Infection Prevention and Control in Patients Undergoing HSCT
Microbiology and Infection Prevention and Control (IPC) Infrastructure Required for Centers Undertaking HSCT
Bacterial Infections
Viral Infections
Fungal Infections
Parasitic Infections
Mycobacterial Infections
Conclusion
Cross-References
References
25 Blood Product Support in HSCT
Introduction
Factors Influencing Transfusion Therapy in HSCT
ABO Blood Group System and HSCT
Blood Component Therapyin HSCT
Red Cell Transfusion
Selection of Rh Type
Platelet Transfusion
Selection of ABO Group and Rh Type
Fresh Frozen Plasma and Cryoprecipitate Transfusion
Granulocyte Transfusion
Modification of Blood Components for HSCT Recipients
Adverse Transfusion Reactions
Transfusion-Transmitted Infections
Cytomegalovirus and HSCT
Platelet Refractoriness
Red Cell Alloimmunization
Autoimmune Hemolytic Anemia and HSCT
Conclusion
Cross-References
References
26 Pediatric Bone Marrow Transplantation
Introduction
Indications of BMT
Allogeneic BMT
Leukemia/Lymphoma
Hemoglobinopathy
Bone Marrow Failure
Primary Immunodeficiency Disorders
Inherited Metabolic Disorders
Autologous HSCT
Matched Sibling Donor BMT
Leukemia/Lymphoma
Hemoglobinopathy
Primary Immunodeficiency Disorders (PIDs)
Inborn Errors of Metabolism
Aplastic Anemia
Unrelated Donor BMT
History
Early Transplants
Introduction of Registries
Umbilical Cord Blood Transplants
Donor Availability
Donor Selection
Algorithm
Cell Source Selection
Graft Manipulation
Major Complications Following Unrelated Donor AlloHCT
Survival Following Unrelated Donor AlloHCT Among Children
Malignant Disease
Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Lymphoma
Nonmalignant Diseases
Hemoglobinopathies
Severe Aplastic Anemia
Other Nonmalignant Diseases
T Cell-Replete Haploidentical SCT
T Cell-Replete Haploidentical SCT: Beijing (GIAC) Protocol
Haploidentical Stem Cell Transplantation with Posttransplant Cyclophosphamide
Leukemia
Thalassemia and Sickle Cell Anemia
Primary Immunodeficiency and Inborn Error of Metabolism
Aplastic Anemia
Haploidentical Stem Cell Transplantation T Cell Depleted
Principles of T Cell Depletion
Pan T Cell Depletion
TCRΞ±Ξ² and B Cell Depletion
NaΓ―ve T Cell Depletion
Infection Risk Post-HSCT in TCD Haplo-HSCT Approaches
Evidence in Children
TCRΞ±Ξ² and B Cell Depletion
Malignant Illnesses
Nonmalignant Illnesses
NaΓ―ve TCD
Autologous HSCT
Lymphoma
Brain Tumors
Neuroblastoma
Other Tumors
Autoimmune Disorders
Gene Therapy and CAR T Cell Therapy
Gene Therapy
General Principles of Gene Therapy
Site of Genetic Modification and Collection of HSPCs
Platform for Gene Therapy
Conditioning Regimen
Early Clinical Applications
Hemoglobinopathies
Severe Combined Immunodeficiency
CAR T Cells
Long-Term Follow-Up of Children Post-BMT
Leukemia/Lymphoma/Solid Tumors
Hemoglobinopathy
Inherited Bone Marrow Failure Syndromes
Primary Immunodeficiency Disorders
Inborn Error of Metabolism
Conclusion
References
27 Nutritional Support and Issues Related to Hematopoietic Stem Cell Transplantation
Introduction
Cancer Associated Malnutrition and Cachexia
Early Screening and Diagnosis
Initiating Nutrition Support
Nutritional Support During GVHD
Role of Parenteral Nutrition
Role of Neutropenic Diet
Nutrition Support of Children Undergoing HSCT
Conclusion
Cross-References
References
28 Psychosocial Management of Patients Undergoing HSCT and Donors of Stem Cells
Introduction
Pre-HSCT Psychiatric Assessment
Psychiatric Morbidities in HSCT
Psycho-pharmacological Management of Patients Undergoing HSCT
Psychological Management of Patients Undergoing HSCT
Post HSCT Adjustment to Life
Patients Informed Decision-Making for HSCT
Donor Finding: Psychiatric/Psychosocial Suitability and Psycho-education of Related Donors
Unrelated Donor Search
Register Resources
The Psychological Experience of Donors
Psychological Issues Associated with Relapse or Recurrence of Disease Following HSCT
Conclusion
Cross-References
References
29 Long-Term Follow-Up and Chronic Complications
Introduction
The Problem
Risk Factors
Primary Disease and Pretransplant Treatment
Conditioning Regimen
Chemotherapy
Radiation Therapy
Immunosuppressive Therapy
Comorbidities
Graft-Related Issues
Long-Term Systemic Toxicity
Cardiovascular System
Risk Factors and Mechanism
Surveillance, Prevention, and Management
Pulmonary Complications
Endocrine Complications
Risk Factors
Thyroid
Growth Issues
Gonadal Toxicity and Sexual Dysfunction
Adrenal Insufficiency
Renal Complications
Second Malignancies
Neurological Complications
Musculoskeletal and Dental Issues
Gastrointestinal
Infectious Diseases
Skin
Sensory Organ Toxicity
Ocular Toxicity
Ototoxicity
Iron Overload
Psychosocial and Quality of Life Issues
Surveillance Plan
Conclusion
Cross-References
References
Part VI: Epidemiology of Bone Marrow Transplantation
30 Bone Marrow Transplantation: Registries and Data Management
Introduction
Overview of Donor Registries
How Does the Search for Matched Unrelated Donor Works?
Responsibilities of Registries and DCs
Data Quality of Donor Registries
Challenges and Opportunities
HLA Diversity
Current State of Unrelated Donor
Process of Donor Management: Confirmatory/Verification typing
Workup/Stem Cell Collection of a Donor
Postponements
Ethical Considerations
Confidentiality
Communication
Direct Contact
Anonymous Correspondence
Communication Prohibited
Right to Withdraw
Consent to Release Personal Information
Courier Transportation
Post Donation and Transplantation
Follow-Up
Reporting Adverse Reactions
DATRI: The Indian Registry
Donor Registration
Operational Challenges
Overview of Patient Registry
EBMT: The European Society of Blood and Marrow Transplantation
The Inception
The Evolution
EBMT Working Parties, Committees, Groups, and Units
Data Collection
Quality Control and Data Auditing
Data Management Challenges
APBMT: The Asia Pacific Blood and Marrow Transplantation Group
CIBMTR: The Center for International Blood and Marrow Transplant Research
WBMT: The Worldwide Network for Blood and Marrow Transplantation
ISBMT: The Indian Society of Blood and Marrow Transplantation
Summary
Cross-References
References
31 Outcomes of Bone Marrow Transplantation
Introduction
Reporting Outcomes in Hematopoietic Cell Transplantation (HCT)
Levels of Evidence in HCT Outcome Reporting
Acute Myeloid Leukemia (AML)
Outcomes of Allo-HCT in AML in Adults
AML in CR1
Advanced AML
Acute Promyelocytic Leukemia
GVHD Prophylaxis
Donor Source
Autologous (Auto) Transplant in AML
Acute Lymphoblastic Leukemia (ALL)
Indications for Transplant
Myeloablative Versus Reduced Intensity Conditioning
Role of Minimal Residual disease in ALL
Role of TKI Use in Ph+ ALL
Donor Type
Myelodysplastic Syndromes (MDS)
Myelofibrosis (MF)
Donor Selection
Conditioning Regimen
Posttransplant Complications
Chronic Lymphocytic Leukemia (CLL)
Lymphomas
Principle of Autologous Hematopoietic Cell Transplantation
Hodgkin Lymphoma (HL)
Diffuse Large B-Cell Lymphomas (DLBCL)
Follicular Lymphomas
Mantle Cell Lymphomas
T-Cell Lymphomas
Aplastic Anemia
HLA-Matched Sibling HCT
Unrelated Donor HCT
Haplo-Identical HCT
Conclusions
Thalassemia
Risk Stratification in Thalassemia for HCT
Conditioning Regimens
Donor Choice
Source of Stem Cells
GVHD Prophylaxis
Overall Long-Term outcomes of HCT in Thalassemia
Sickle Cell Disease (SCD)
HCT in Children with SCD
HCT in Adult SCD with Myeloablative Conditioning
Unrelated Donor HCT in Children
Nonmyeloablative Matched Sibling Donor HCT in Adults
Related Haploidentical HCT
Conclusions
Multiple Myeloma
Initial Induction Prior to Autologous Transplant
Stem Cell Dose
Conditioning Regimen
Timing of Autologous HCT
Tandem Transplant
Outcomes and Treatment of Relapse after Auto-HCT
Maintenance Therapy After Transplant
Allogeneic Transplant in Myeloma
Scleroderma and Autoimmune Diseases
CrohnΒ΄s Disease
Multiple Sclerosis
Transplant in Solid Organ Malignancies
Breast
Male Germ Cell Tumors
Conclusion
Cross-References
References
Part VII: Newer Trends
32 The Future of Transplantation: Hope, Investigative Discipline, and Fairness
Introduction
Donor and Graft Choices
Prevention of Relapse
Graft-Versus-Host Disease
Chronic GVHD
Limiting Transplant-Associated Toxicities
Transplant Successes Come at Great Cost
Cross-References
References
33 Cellular Therapy
Introduction
CAR-T Cell Therapy
Manufacturing
Lymphodepletion
Cytokine Release Syndrome and Neurotoxicity
Anti-CD19 CAR-T
B Cell Non-Hodgkin Lymphoma
CD19 CAR-T in B Cell Lymphomas
CAR-T Cells in Follicular Lymphoma
CAR-T Cells in Mantle Cell Lymphoma
Novel CAR-Ts in NHL
CAR-T Cell Therapy in Acute Lymphoblastic Leukemia
Post-CAR-T Management in B Cell ALL
Novel Targets in B Cell ALL
T Cell Acute Lymphoblastic Leukemia
CAR-T Cell Therapy in Chronic Lymphocytic Leukemia
CAR-T in Multiple Myeloma
Challenges and Future Perspectives
Conclusion
Cross-References
References
Index