Blood and Marrow Transplant Handbook: Comprehensive Guide for Patient Care

Preface
Acknowledgments
Contents
Contributors
Chapter 1: Overview of Hematopoietic Cell Transplantation and Cellular Therapy
Introduction
Key Principles
Research Efforts in HCT
Horizons/Challenges
References
Chapter 2: The Business of Cellular Therapy and Hematopoietic Cell Transplantation
Introduction
Increase in Utilization and Impact of HCT on National Health-Care Costs
Complexity of Care Increases Costs
Contracts and Reimbursement Strategies
Integrated Structure for Contract Management
Payor Types
Clinical Trials
Chimeric Antigen Receptor T-Cell Therapy (See Also Chapt. 52 and 58)
Quality
Future Considerations
Summary
References
Reference for Slides
Websites
Chapter 3: Hematopoietic Stem Cell Sources and Donor Selection
Introduction
Stem Cell Sources
Donor Selection (See Fig. 3.1)
Other Considerations
Donor Complications
References
Chapter 4: Pretransplant Assessment for Hematopoietic Cell Transplantation Recipients and Donors
Introduction
Indications for Transplantation
Patient Evaluation
General Guidelines for Patient Eligibility
Donor Evaluation for Allo-HCT
References
Chapter 5: Social Work: Evaluation and Social Supports
Introduction
Psychosocial Evaluation and Assessment
Preparation and Planning
Active Treatment – Inpatient and Outpatient
Immediate Short Term
Long Term/Survivorship
End-of-Life Care
Palliative Care and Hematologic Malignancies (See Also Chap. 48)
Caregiving Needs and Requirements
Psychosocial Impact of Caregiving and Protective Factors
References
Chapter 6: Conditioning Regimens
Introduction
Conditioning Agents
Antiemetic dosing
Chemotherapy Dosing in Conditioning Regimens [15, 22, 23, 35, 39–52]
References
Chapter 7: Nutrition
Introduction
Low Bacteria Diet
Graft-Versus-Host Disease Diet
Goals of Nutrition During HCT
Use of Total Parenteral Nutrition
Use of Enteral Nutrition
Catabolic/Anabolic States
Discussion of Glutamine Controversy
Microbiome
References
Chapter 8: Physical and Occupational Therapy
Introduction
Effects of Cancer and HCT: Serious Adverse Events (SAEs) and Impairments Impacting Functional Ability and Rehabilitation
The Role of Physical and Occupational Therapy Services
Physical and Occupational Therapy Interventions
Conclusion
References
Chapter 9: Adolescent and Young Adult Concerns
Introduction
Medical
Emotional/Psychological
Physical
Neurocognitive
Social
Reproductive (see also Chaps. 39 and 40)
Financial
Lifestyle Issues
Late Effects (see also Chap. 49)
Care Community
AYA-Specific Resources
Bibliography
Chapter 10: Infection Prevention and Prophylaxis
Introduction
Herpes Simplex Virus (HSV)/Varicella Zoster Virus (VZV) Prophylaxis/Prevention
Cytomegalovirus (CMV) Disease Prevention
Antibacterial Prophylaxis
Encapsulated Organism Prophylaxis for Patients with Chronic GvHD
Antifungal Prophylaxis
Pneumocystis jiroveci Prophylaxis
Toxoplasma gondii
Viral Hepatitis
References
Chapter 11: Graft-Versus-Host Disease (GvHD) Prophylaxis
Introduction
Risk Factors for GvHD
aGvHD Prophylaxis
Common aGvHD Prophylaxis Regimens
cGvHD Prophylaxis
Medication Mechanisms, Doses, Interactions, and Toxicities
Transplant Complications Requiring Change in GvHD Prophylaxis
References
Chapter 12: Transfusion Medicine
Introduction
Pre-HCT Considerations
Day 0 Considerations
Immunohematology Basics
Transfusion Reactions [10, 11]
Post-HCT Considerations
Post-Engraftment Considerations
References
Chapter 13: Anticoagulation and Antiplatelet Guidelines
Introduction
Types of Antiplatelet Therapy
Types of Anticoagulants and Important Drug Interactions
Venous Thromboembolism (VTE)
Atrial Fibrillation/Flutter
Prosthetic Heart Valves
Bridging Anticoagulation
Arterial Thrombosis
References
Chapter 14: Engraftment
Introduction
Engraftment
Complications of Engraftment
Foundation for the Accreditation of Cellular Therapy (FACT) Standards for the Review of Engraftment
References
Chapter 15: Acute Myeloid Leukemia and Allogeneic Hematopoietic Cell Transplant
Introduction
Risk Stratification
Role of Transplant as Consolidation Therapy
AML Disease Assessment Prior to Allogeneic HCT
MRD in Transplant
FLT-3-Mutated AML
Targeted Therapy
Citations
Chapter 16: Acute Lymphoblastic Leukemia
Introduction
MRD Assessments and HCT Decision-Making
The Impact of Age on HCT Decision-Making
The Impact of Immunotherapy Utilization on HCT Decision-Making
Ph+ ALL
Ph-like ALL
Summary
References
Chapter 17: Hodgkin Lymphoma and Non-Hodgkin Lymphoma
Introduction
Hodgkin Lymphoma
Diffuse Large and High-Grade B-Cell Lymphomas
Follicular and Low-Grade NHL
Mantle Cell Lymphoma
Peripheral T-Cell Lymphoma
Primary CNS Lymphoma
NHL with Secondary CNS Involvement
Restaging Guidelines After HCT in Systemic Lymphoma
References
Chapter 18: Multiple Myeloma
Introduction
Assessment of Transplant Eligibility
Induction Therapy
Stem Cell Mobilization
High-Dose Therapy
Supportive Care
Maintenance Therapy After AutoHCT
Response Criteria
Salvage AutoHCT
Adoptive Cellular Therapies
References
Chapter 19: HCT for Germ Cell Tumors
Introduction
Diagnosis and Staging
Initial Therapy for Disseminated Testicular Cancer
Salvage Therapy for Relapsed/Refractory Disease
Salvage Strategies After Failure of High-Dose Chemotherapy
References
Chapter 20: Hematopoietic Cell Transplant for Myelofibrosis
Introduction
Risk Classification
Nontransplant Options for Treatment
Indications for Transplant
Timing of Transplantation
Special Considerations in Work-up
Conditioning Regimens
Transplant Outcomes (Table 20.2)
Pretransplant Therapy with JAK-inhibitors (Table 20.3)
Other Post-Transplant Considerations
Secondary MF (PV and ET)
Leukemic Transformation
References
Chapter 21: Chronic Myeloid Leukemia
Introduction
Making the Diagnosis and Monitoring Response in CML
Defining Response in CML
Risk Stratification in CML
Response Milestones and Kinetics: Treatment Guidelines
Treatment-Free Remission (TFR)
Resistance Testing, Mutations, and Subsequent Lines of Therapy
TKI Therapy: Imatinib (Gleevec®)
TKI Therapy: Nilotinib (Tasigna®)
TKI Therapy: Dasatinib (Sprycel®)
TKI Therapy: Bosutinib (Bosulif®)
TKI Therapy: Ponatinib (Iclusig®)
Other Recent Therapies for CML: Omacetaxine (Synribo)
Novel Therapy for CML: Asciminib (ABL001)
Role of Allogeneic Transplantation in CML in the Era of TKIs
References
Chapter 22: Chronic Lymphocytic Leukemia
Introduction
References
Chapter 23: Hematopoietic Cell Transplant for Severe Aplastic Anemia
Introduction
Diagnosis of SAA
Treatment
HCT from HLA-Matched Unrelated Donors (M-URD)
M-URD HCT as First-Line Therapy in Children
Alternative Donor Transplantation for SAA
Conclusion
References
Chapter 24: Inherited Disorders
Introduction
Primary Immunodeficiencies (PID)
Inborn Errors of Metabolism (IEM)
Inherited Bone Marrow Failure Syndromes
Hemoglobinopathies
References
PID
IEM
Cytopenias
Hemoglobinopathies
Chapter 25: Hematopoietic Cell Transplant and Cellular Therapies for Sickle Cell Disease
Introduction
HLA-Matched Related Donor Transplant (MRD) in Children
HLA-Matched MRD Transplant in Adults
Alternative Donor Sources
Gene Therapy
Conclusion
References
Chapter 26: Radiology Pearls for the Transplant Provider
Introduction
Chest
Neutropenic/pre-engraftment phase (0–30 days)
Early phase (1–3 months)
Late phase (3 months–1 year)
Abdomen
References
Chapter 27: Acute Graft-Versus-Host Disease (GvHD)
Introduction
Pathophysiology
Risk Factors [5–8]
Incidence and Mortality [11, 12]
Clinical Presentation (See Table 27.1)
Evaluation
Staging/Grading
Biomarkers
Recent/Active Multicenter Trials
Treatment for the New Diagnosis of Acute GvHD
Steroid-Refractory Disease
Autologous GvHD
Conclusions
References
Chapter 28: Chronic Graft-Versus-Host Disease
Introduction
Pathophysiology (See Fig. 28.1)
Epidemiology and Risk Factors
Symptoms and Severity
Posttransplant Follow-Up and Monitoring for cGvHD
Prophylaxis (See Also Chap. 11)
Treatment
Concurrent Supportive Therapy for cGvHD (See Also Chap. 10)
Research Areas and Potential Therapeutic Targets
Prognosis
References
Chapter 29: Immune Reconstitution
Introduction: The Human Immune System
Assays for Monitoring Immune Reconstitution
Reconstitution of the Innate Immune System
Reconstitution of the Adaptive Immune System
Factors Affecting Immune Reconstitution
Patterns of Immune Reconstitution
Immune Enhancement Therapy
Clinical Evaluation for Immune Reconstitution
Conclusion
References
Chapter 30: Infectious Complications
Introduction
Empiric Antimicrobial Therapy and Evaluation of Neutropenic Fever [33]
Treatment of Common Specific Infections
References
Chapter 31: Oral Complications
Introduction
Oral Mucositis
Infections
Predental Procedures
Taste Alterations
Discharge Instructions
Chronic Graft-Versus-Host Disease (See Also Chap. 28)
References
Additional Readings
Chapter 32: Gastrointestinal Complications
Introduction
Upper Gastrointestinal
Lower Gastrointestinal
Hepatobiliary Diseases
References
Chapter 33: Pulmonary Complications
Introduction
Pulmonary Function Tests
Bronchoscopy
Idiopathic Pneumonia Syndrome (IPS)
Diffuse Alveolar Hemorrhage (DAH)
Bronchiolitis Obliterans Syndrome (BOS)
Cryptogenic Organizing Pneumonia (COP)
References
Chapter 34: Cardiovascular Complications
Introduction
Baseline Cardiac Evaluation
Congestive Heart Failure (CHF)
Cardiac Arrhythmias
Myocardial Ischemia and Coronary Artery Disease
Systemic Arterial Hypertension
Pericardial Disease
Effect of Chest Wall Radiation
Survivorship (See Also Chap. 51)
References
Chapter 35: Kidney Disease in Hematopoietic Cell Transplantation
Introduction
Definitions of AKI and CKD
Kidney Disease in HCT: Incidence and Risk
General Classification of Causes of AKI and Basic Evaluation
Timing and Cause of Renal Injury
Evaluation and Management of Common Causes of AKI
Evaluation and Management of Common Causes of CKD
References
Chapter 36: Neurological Complications
Introduction
Noninfectious Treatment-Related Neurotoxicity
Neuro-infectious Complications
Cerebrovascular Complications
Radiation-Induced Complications
Post-Transplant Lymphoproliferative Disorder
Metabolic Complications
Conclusion
References
Chapter 37: Endocrine Complications Following Hematopoietic Cell Transplantation
Introduction
Metabolic Syndrome
Diabetes Mellitus [3, 15, 22, 23]
Adrenal Insufficiency [5, 8, 15, 17]
Thyroid Dysfunction [7, 8, 15, 24]
Skeletal Complications [8, 9, 12, 15, 27, 28]
Hypogonadism (See Chaps. 39 and 40)
References
Chapter 38: Thrombotic Microangiopathies
Introduction
Clinical Presentation
Risk Factors
Classification
Etiology
Diagnosis
Treatment
References
Chapter 39: Women’s Health Care
Introduction
Amenorrhea
Primary Ovarian Insufficiency (POI)
Contraception
Gynecology Preventive Practice Guidelines
Hormone Therapy
Sexual Well-Being
GvHD of the Female Genital Tract
Emergent Therapy for Suppression of Heavy Menstrual Bleeding with Thrombocytopenia
References
Chapter 40: Men’s Health for Hematopoietic Cell Transplant Patients
Introduction
Erectile Dysfunction (ED) [1–3]
Infertility
Hypogonadism [6]
Enlarged Prostate/Benign Prostatic Hyperplasia (BPH)
Prostate Cancer Screening
References
Chapter 41: Psychiatric Complications
Introduction
Delirium and Altered Mental Status
Depression
Anxiety
Sleep Disorders
Mania, Psychosis, and Substance Abuse
Drug Interactions and Dose Adjustments
Capacity
Psychiatric Consultation
References
Chapter 42: Graft Failure
Introduction
Graft Failure and Poor Graft Function
References
Chapter 43: Second Primary Malignancies
Introduction
General Risk Factors
Incidence
Onset
Types of Second Primary Malignancies
Survival Following Secondary Malignancies
Screening and Preventive Practices
References
Chapter 44: Relapse After Hematopoietic Cell Transplantation
Introduction
Biology of Relapse After HCT
Risk of Relapse After HCT
Monitoring for Relapse After HCT (See also Chap. 59)
Prevention of Relapse After HCT
Treatment of Relapse After Autologous HCT
Treatment of Relapse After Allogeneic HCT
References
Chapter 45: Safe Pain Management with Opioids in Posttransplant Patients
Introduction
Pain Assessment
Opioid Overview
Universal Precautions for Prescribed Opioids
Addressing Aberrant Behaviors
Opioid Tapering
Opioid Use Disorder
Patient Education
Additional Provider Resources
References
Chapter 46: Complementary Medicine: Acupuncture
Introduction
Integrative Oncology
Use of Acupuncture: Symptom Support in Cancer Care and Hematopoietic Cell Transplantation (HCT)
Side Effects and Contraindications
Conclusion
References
Chapter 47: Complementary Medicine: Medications and Supplements
Introduction
References
Chapter 48: Complementary Medicine: Cannabinoids and the Hematopoietic Cell Transplant (HCT) Recipient
Introduction
References
Chapter 49: Management of Neurocognitive Effects and Fatigue During and After Hematopoietic Cell Transplant
Introduction
Neurocognitive Dysfunction or “Chemo Brain”
Fatigue
Pharmacologic Treatments
Conclusion
Suggested Reading
Chapter 50: Palliative Care
Introduction
Core Functions of Palliative Care Related to Direct Patient Care
Advance Care Planning
Support for Caregivers
Common HCT-Associated Side Effects [9–12]
Summary
References
Chapter 51: Long-Term Follow-Up and Survivorship
Introduction
Infection [7–11] (See Also Chap. 30)
Cardiovascular [7, 12–17] (See Chap. 34)
Pulmonary [7, 18, 19] (See Also Chap. 33)
Neurologic [7, 20–24] (See Also Chaps. 36 and 49)
Hepatic [7, 25–27]
Ocular [7, 29–31]
Oral [7, 32–34] (See Also Chap. 31)
Endocrine [7] (See Also Chap. 37)
Musculoskeletal Complications [7, 44–47] (See Also Chaps. 37 and 39)
Second Malignancies [7, 48–50] (See Also Chap. 43)
Sexuality and Reproductive Issues (See Chaps. 39 and 40 for In-Depth Discussion and Review) Psychosocial Concerns [51–53]
References
Chapter 52: CAR T Cells for Hematologic Malignancies
Introduction
References
Chapter 53: Natural Killer Cell Therapy in Allogeneic Hematopoietic Cell Transplantation
Introduction
NK Cell Biology
Consideration of Natural Killer Cell Alloreactivity
Cytokines to Augment NK Cell Activity
Enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC)
NK Cells as a Cell-Based Therapy
Conclusion: Ongoing Challenges and Future Directions
References
Chapter 54: Mesenchymal Stromal Cells: Impact on Hematopoietic Cell Transplantation
Introduction
Biological Properties of MSCs and Impact on Hematopoiesis
MSC for the Treatment of Acute GvHD
MSC for Prophylaxis of Acute GvHD
Conclusions
References
Chapter 55: T-Cell Therapeutics: Donor Lymphocyte Infusion, Cytotoxic T-Lymphocyte Infusion, and Other Non-CAR T-Cell Therapies
Introduction
Donor Lymphocyte Infusion
Regulatory T (Treg) Cells
Cytotoxic T Lymphocytes for Viral Infections
TCR-Modified T-Cell-Associated Toxicities
References
Further Readings
Donor Lymphocyte Infusion
Regulatory T (Treg) Cells
Cytotoxic T Lymphocytes for Viral Infections
T-Cell Receptors-Gene-Modified T Cells for Cancer Treatment
Chapter 56: Dendritic Cell Vaccines
Introduction
Dendritic Cells (DCs)
The Exploitation of Dendritic Cell Biology and Generation of Dendritic Cell Vaccines
Dendritic Cell Vaccines Currently in Use or Late Clinical Trials
Challenges in Implementation and Efficacy
Combination Dendritic Cell Vaccines
Role in Infectious Disease
Potential Role in Graft-Versus-Host Disease (GvHD)
References
Chapter 57: BiTEs, DARTs, and Peri-Transplant Minimal Residual Disease
Introduction
Definitions (See Fig. 57.1 for Schematic Representation of Different Bispecific Antibody Constructs)
BiTEs and DARTs That Are FDA Approved or Have Preliminary Results from Clinical Trials (See Table 57.1)
Clinical Efficacy of Blinatumomab (Blincyto®)
Addressing Pre-Transplant MRD with Bispecific Antibody Therapy
Re-Emergence of Leukemia Post-HCT
Future Directions and Challenges
References
Chapter 58: CAR T Toxicity Management: Cytokine Release Syndrome and Neurotoxicity
Introduction
Cytokine Release Syndrome (CRS)
Neurotoxicity
References
Chapter 59: Molecular Testing for Post-transplant Disease Surveillance
Introduction
Molecular Markers for Post-transplant Surveillance
Short Tandem Repeats (STRs)
Single-Nucleotide Polymorphisms (SNPs)
Somatic Tumor-Specific Mutations
Sample Types for Post-transplant Surveillance
Donor
Host
Whole Blood/Bone Marrow Chimerism Testing Versus Lineage-Specific Chimerism Testing
Molecular Technologies for Post-transplant Surveillance
Quantitative PCR-Based STR Analysis to Assess Chimerism [6]
Next-Generation Sequencing
Other Commonly Utilized Laboratory Technologies
Clinical Utility and Limitations
Post-HCT Chimerism Analysis
Post Solid Organ Transplant Chimerism Analysis
Post-HCT MRD Analysis
References
Chapter 60: Management of Immune Compromised Transplant and Immune Effector Cell Treated Patients in the Setting of the COVID-19 Viral Pandemic: The OHSU Experience
Introduction
Patient Selection
Autologous Hematopoietic Cell Transplant Procedures
Allogeneic Hematopoietic Cell Transplant Procedures
Immune Effector Cell/Chimeric Antigen Receptor–T Cell Therapy
Inpatient Care Management
Outpatient Care Management
Clinical Trials
Personnel Management
Recommended Readings
Appendix 1: The Vocabulary of Transplant
Appendix 2: Procedure – Bone Marrow Aspirate and Biopsy
Appendix 3: Procedure – Lumbar Puncture
Appendix 4: Procedure – Ommaya Reservoir Tap
Appendix 5: Procedure – Skin Biopsy
Appendix 6: OHSU Food Safe Diet
Appendix 7: OHSU Low-Bacteria Diet
Appendix 8: OHSU Graft-Versus-Host Disease Diet
Appendix 9: OHSU Vaccine Guidelines
Appendix 10: OHSU Donor and Stem Cell Source Selection in Allogeneic Hematopoietic Progenitor Cell Transplantation
Index