Hematopoietic Cell Transplantation for Malignant Conditions, 1e

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Copyright
Hematopoietic Cell Transplantation for Malignant Conditions
List of Contributors
1 - History and Current Status of Hematopoietic Cell Transplantation
	Introduction
		BMT Developments in 1950s to Early 1960s
		The Significance of HLA Matching in Transplant
		Late 1960s: The First Successful HLA-Matched Sibling BMTs
		Late 1970s to Mid-1980s: Use of Unrelated Donors
		1980−90: Use of PB as Autograft
		Early 1990s: Rapid Increase in Allogeneic Transplantation Using PB Grafts
		Haploidentical Stem Cell Transplantation
		History of Umbilical Cord Blood Transplant
		Late 1990s to Early 2000s: Introduction of RIC
		Origin of Donor and Transplant Registries
	Conclusion
2 - Pharmacology of Drugs Used in Hematopoietic Cell Transplantation
	Introduction
	Immunosuppressants
		Cyclosporine
			Pearls
		Tacrolimus
			Pearls
		Methotrexate
		Mycophenolate
		Sirolimus
			Pearls
		Cyclophosphamide
		Antithymocyte Globulin
			Pearls
		Alemtuzumab
			Pearls
		Corticosteroids
			Pearls
	Antimicrobial Agents
		Trimethoprim/Sulfamethoxazole
		Piperacillin/Tazobactam
			Pearl
		Cephalosporins
		Carbapenems
		Vancomycin
			Pearl
		Metronidazole
			Antivirals
				Acyclovir/valacyclovir.Acyclovir is a nucleoside analog that possesses activity against the herpes family of viruses, including ...
				Ganciclovir/valganciclovir.Ganciclovir is similar in structure to acyclovir, with the addition of a hydroxymethyl group. Gancicl...
				Foscarnet.Foscarnet is a pyrophosphate analog with inhibitory activity against all the herpesviruses. It is effective for treatm...
				Cidofovir.Cidofovir is a cytidine nucleotide analog with inhibitory activity against human herpes, papilloma, polyoma, pox, and ...
				Letermovir.Letermovir inhibits the CMV DNA terminase complex (UL56) which is required for viral DNA processing and packaging. Th...
			Antifungals
				Amphotericin B.Amphotericin B is a polyene antifungal that exerts its activity by binding to ergosterol in fungal cell membranes...
				Triazoles.Availability of the triazole antifungal agents made a substantial impact on antifungal treatment approaches because of...
				Echinocandins.Caspofungin, micafungin, and anidulafungin are the three echinocandins available for use. These agents target 1,3-...
	Antidiarrheal Agents
		Loperamide
		Diphenoxylate and Atropine
		Octreotide
	Miscellaneous
		Defibrotide
		Ursodiol
		Deferasirox
		Intravenous Immune Globulin
		Palifermin
3 - High-Dose Chemotherapy Regimens
	Goals of Conditioning Regimens
	Types of Conditioning Regimens
	Nonchemotherapy Agents in Conditioning Regimens
		Total-Body Irradiation
		Radioisotopes and Radioimmunotherapy
		90Y-Ibritumomab Tiuxetan
	Chemotherapy Agents in Conditioning Regimens
	Alkylating Agents
		Busulfan
		Cyclophosphamide
		Ifosfamide
		Melphalan
		Thiotepa
		Carmustine
		Bendamustine
	Antimetabolites
		Fludarabine
		Clofarabine
		Cytarabine
		Gemcitabine
	Platinum Agents
		Carboplatin
	Plant Alkaloids
		Etoposide
	Anti-T Cell Antibodies
	Monoclonal Antibodies
		Rituximab
	Dosing Considerations
		Organ Dysfunction
			Renal
			Hepatic
		Dosing Principles
		Dosing in Obese Patients
4 - The Role of Radiation Therapy in Hematopoietic Stem Cell Transplantation
	Total-Body Irradiation Therapy
		Myeloablative Conditioning Regimens
		Reduced-Intensity Conditioning Regimens
		CNS Leukemic Involvement
			Toxicity after HSCT: contributions from TBI
	The Role of RT Among Patients with Hodgkin Lymphoma and Non-Hodgkin Lymphoma Undergoing HSCT
		Hodgkin Lymphoma
		Non-Hodgkin Lymphoma
		Toxicity Among HL and NHL Patients
	Conclusions
	Disclosure Statement
5 - Sources of Cells for Hematopoietic Cell Transplantation: Practical Aspects of Hematopoietic Cell Collection
	Introduction
	Sources of Cells for Allogeneic Transplantation
		Bone Marrow
		Peripheral Blood
		Comparisons of Bone Marrow Versus Peripheral Blood
		Umbilical Cord Blood
	Sources of Cells for Autologous Transplantation
		Growth Factor Mobilization
		Chemotherapy Plus GF Mobilization
		Growth Factor Plus CXCR4 Antagonist
		Comparison of Mobilization Strategies
		Mobilization Failures
6 - Patient and Donor Selection and Workup for Hematopoietic Cell Transplantation
	Disease-Specific Factors
		Demographic Factors
		Comorbidities
		Patient-Reported Outcomes and Socio-Economic Factors
		Tools
		HLA Typing and the Search Procedure
	Donor Selection and Workup
		Donor Selection
			Donor type
		Donor Workup
			Donor suitability
			Risk to recipient
			Risk to the donor
			Donor assessment
			Conflict of interest
			Donor follow-up
7 - T-Cell Replete Haploidentical Transplantation
	Introduction
	Posttransplantation Cyclophosphamide-Based Platform
		Haplo-SCT PT-Cy in Nonmalignant Diseases
	Conclusions
8 - Umbilical Cord Blood Transplantation
	Introduction
		History
		Cord Blood Collection, Processing, and Storage
	Cord Blood Unit Selection
		Conditioning Regimens
			MAC regimens
			Reduced-intensity conditioning and non-myeloablative regimens
			Antithymocyte globulin
			Graft-versus-host disease
			Immune reconstitution
	Future of Cord Blood Transplantation
9 - Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia
	Introduction
	Mechanisms of Allo-HSCT in AML
	Acute Myeloid Leukemia—Disease and Classification
	Risk Stratification of Acute Myeloid Leukemia
	Dynamic Risk Prognostication
	Indications for Allo-HSCT
	Conditioning Regimens
	Myeloablative Conditioning
	Reduced Intensity Conditioning
	Nonmyeloablative Conditioning
	Alternative Donor Transplantation
	Transplantation in Induction Failure or in Relapse
	Management of Posttransplant Relapse
	Preventing AML Relapse with Post-HSCT Maintenance Therapy
	Future Direction
10 - Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia
	Introduction
		Allo-HCT in CR1 for Ph-Negative ALL
		Allo-HCT in CR1 for Ph-Positive ALL
		Question 1: Is Transplant Mandatory for all Ph-Positive ALL Patients
		Question 2: Is Posttransplant TKI Maintenance Necessary
		Question 3: Is There a Role for Autologous HCT for Ph-Positive Patients
	Allogeneic HSCT Beyond CR1
	Optimal Conditioning and Donor Selection for allo-HCT for ALL
		Choice of Myeloablative Conditioning
		Choice of RIC
		Alternative Donors
		MUD Transplants
		UCB Transplants
		Haploidentical Transplants
	Advances in the Field of ALL
		Novel ALL Entities and Role of Allo-HCT for These Entities
			Early T precursor ALL
			Philadelphia-like ALL (BCR-ABL–like ALL)
		Incorporation of Novel Agents into the Treatment Algorithm of ALL
		Conclusion
11 - Hematopoietic Cell Transplantation for Myeloproliferative Neoplasms
	Introduction
	Nontransplant Therapies in MF
	HCT in MF
		HCT in Chronic Phase of MPN
		Risk Stratification of MF
		JAKi Therapy versus HCT
		Role of JAK Inhibitors in HCT
		Optimal Conditioning Therapy for HCT for MF
			What is the preferred graft source in MF
			Splenectomy in the era of JAK inhibitors
		Alternative Donor Transplantation in Myelofibrosis
		Transplantation for MPN in AP/BP
	Conclusions
12 - Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia
	Introduction
	Autologous Hematopoietic Cell Transplant
	Allogeneic Hematopoietic Cell Transplant
		Who Is Considered a Candidate for Allo-HCT in the Era of Novel Therapies
		Richter Syndrome
		Does the Intensity of the Condition Regimen Matter
		Novel Therapies in the Current Era
		Ibrutinib
		Idelalisib
		Venetoclax
		Chimeric Antigen Receptor–T Cells
		Other Experimental Agents
	Discussion
13 - Allogeneic Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome
	Introduction
	Who Is a Candidate for Allo-HCT
		Patient-Related Factors
		Disease Characteristics
			Treatment-related MDS
			Hypoplastic MDS
			MDS originating from congenital mutations
	Donor Selection
	Selecting Hematopoietic Cell Source
	The Role of Pretransplant Debulking Treatment
	Selection of the Intensity of Conditioning Regimens
	Posttransplantation Strategies
		Monitoring Residual Disease and Mixed Chimerism
		Prevention of Relapse after Allo-HCT
		Management of Posttransplant Relapse
		Management of Posttransplant Iron Overload
14 - Autologous Hematopoietic Stem Cell Transplantation for Non-Hodgkin Lymphoma
	Introduction
	Diffuse Large B Cell Lymphoma (DLBCL)
	Follicular Lymphoma
	Mantle Cell Lymphoma
	Marginal Zone Lymphoma
	Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia
	Posttransplant Lymphoproliferative Disorder
	Plasmablastic Lymphoma
	Conclusion
15 - Allogenic Transplant for Non-Hodgkin Lymphoma
	Introduction
	B-Cell Lymphomas
	Allo-HCT for DLBCL
		Allo-HCT for DLBCL After Failed Auto-HCT
		Summary: DLBCL
	Follicular Lymphoma
		Overview of FL
		Allo-HCT for Relapsed, Refractory FL: Prospective Studies
		Allo-HCT for Relapsed, Refractory FL: Retrospective Studies
		Summary: FL
	Mantle Cell Lymphoma
		Overview of MCL and Nontransplantation Options for Frontline Therapy
		Allo-HCT for Relapsed, Refractory MCL
		Summary: MCL
	Allo-HCT in Other Rare Variants of B-Cell NHL
		T-Cell Lymphomas
		Allogeneic Transplant in First Remission (Prospective Studies)
	Relapsed/Refractory T-cell Lymphoma
		PTCL-NOS, ALCL, and AITL
		Allogeneic Transplant for Natural Killer/T-Cell Lymphoma
		Allogeneic Transplant for Hepatosplenic T-Cell Lymphoma
		Allogeneic Transplant for Adult T-Cell Leukemia/Lymphoma
		Allogeneic Transplant for Rare Mature T-Cell Neoplasms
		Allogeneic Transplant in Older Patients
		Future Directions in Allo-HCT for NHL
16 - Hematopoietic Stem Cell Transplantation for Hodgkin Lymphoma
	Role Autologous Stem Cell Transplantation in HL
	Factors That Predict Recurrence After Transplantation
		Objectives of Salvage Chemotherapy Before Transplantation
		Impact of Conditioning Regimen
		Poor-Risk HL and Autologous Transplant
		Indications for Peritransplant Radiation
		Posttransplant Maintenance With Brentuximab Vedotin
	Allogeneic Hematopoietic Transplantation in HL
		Myeloablative Versus Reduced-Intensity Conditioning Regimens for HL
	Alternative Donor Allogeneic Transplantation in HL
		Use of Donor Lymphocyte Infusions in HL
	Complications Associated With Transplantation Specific to HL
		Idiopathic Pneumonia Syndrome After Autologous Transplant
		Secondary Malignancy
		GVHD in Association With Checkpoint Inhibition
17 - Hematopoietic Cell Transplantation in Patients With Multiple Myeloma
	Autologous Stem Cell Transplant: The Standard of Care in Multiple Myeloma
	Autologous Stem Cell Transplant in the Era of Novel Agents
	Autologous Hematopoeitic Cell Transplant as Part of First-Line or Second-Line Therapy
	Single Versus Tandem Autologous Hematopoietic Cell Transplant
	The Role of Salvage Autologous Hematopoietic Cell Transplant in MM
	Allogeneic Hematopoietic Cell Transplantation for MM
	Conclusions
18 - Hematopoietic Cell Transplantation for Light-Chain Amyloidosis
	Introduction
		History and Current Data of Transplantation for AL Amyloidosis
		Mobilization and Collection of CD34+ Cells
		Do Patients Need Induction Chemotherapy Before Auto-HCT
		Conditioning Chemotherapy
		Supportive Care During Transplant
		Posttransplant Consolidation
		Response to Treatment—Hematologic and Organ Responses
		Role of Allogeneic Transplant in AL Amyloidosis
		Role of Solid Organ Transplant in AL Amyloidosis
		Relapse and Retreatment after Transplant
	Conclusions
	Selected Reading
19 - Hematopoietic Stem Cell Transplantation for Rare Hematological Malignancies
	Introduction
	Systemic Mastocytosis
	Langerhans Cell Histiocytosis
	Chronic Myelomonocytic Leukemia
	Hypereosinophilic Syndrome
	Primary Central Nervous System Lymphoma
	Adult T-Cell Leukemia/Lymphoma
	NK Cell Neoplasms
	Blastic Plasmacytoid Dendritic Cell Neoplasm
	Hepatosplenic T-Cell Lymphoma
	Subcutaneous Panniculitic T-Cell Lymphoma
	Cutaneous T-cell Lymphomas
20 - Hematopoietic Cell Transplantation for Germ Cell Tumors and Other Adult Solid Tumors
	Novel HDC Approaches to Relapsed GCT
		One or More Cycles of HDC
		Randomized Trials of HDC in the Salvage Setting
		First-Line High-Dose Chemotherapy for Poor-Risk Non Seminomatous Germ Cell Tumors (NSGCT)
	Breast Cancer
		High-Dose Chemotherapy in HRPBC
		Metastatic Breast Cancer
		Autologous Transplantation in Other Solid Tumors
		Allogeneic Stem Cell Transplantation for Solid Tumors
21 - Hematopoietic Cell Transplantation for Pediatric Solid Tumors
	Hematopoietic Cell Transplantation for Pediatric Solid Tumors
		Neuroblastoma
		CNS Tumors
		Medulloblastoma and CNS Embryonal Tumors, NOS
		Atypical Teratoid/Rhabdoid Tumor
		High-Grade Glioma
		Germ Cell Tumors
		Sarcomas
		Ewing Sarcoma
		Osteosarcoma
		Rhabdomyosarcoma
		Nonrhabdomyosarcoma Soft Tissue Sarcomas
		Wilms Tumor
22 - Pathophysiology and Management of Graft-Versus-Host Disease
	Acute GVHD
		Introduction
		Definition
		Epidemiology
		Risk Factors
	Pathophysiology
	Clinical Manifestations
		Skin Manifestations
		Hepatic Manifestations
		Gastrointestinal Tract
		Endocrine and Hematologic Manifestations
	Grading of Acute GVHD
	Prevention of aGVHD
		Pharmacologic Immunosuppression
		T-Cell Depletion
		Novel Strategies for Prevention
	Treatment
		First-Line Therapy for aGVHD
			Stage I aGVHD
			Stage II aGVHD
		Second-Line Therapy for aGVHD
	Future Directions
		Biomarkers in GVHD
		Future Targets in aGVHD
	aGVHD (Conclusion)
	Chronic GVHD: Introduction
	Chronic GVHD: Risk Factors and Epidemiology
	Chronic GVHD: Pathophysiology
		Introduction
	Chronic GVHD: Clinical Manifestations
		Oral Mucosal Involvement
		Skin and Soft Tissues
		Ocular Involvement
		Hepatic and Gastrointestinal Involvement
		Pulmonary Complications
		Neuromuscular and CNS Involvement
		Immunodeficiency
		Nonimmune, Late Effects after Transplantation and Chronic GVHD
	Diagnostic Criteria for Chronic GVHD
	Chronic GVHD Prophylaxis and Treatment
	Future Directions and Novel Therapeutics
	Biomarkers
	Discussion
23 - Graft Failure
	Definitions
	Graft Rejection
	Poor Graft Function
	Clonal Hematopiesis and Graft Failure
	Treatment
		Graft Rejection
	Poor Graft Function
		Stem Cell Boost From Original Donor
		Mesenchymal Stromal Cells
	Approach
24 - Miscellaneous Complications Related to Hematopoietic Cell Transplantation
	Venoocclusive Disease (Sinusoidal Obstruction Syndrome)
	Transplant-Associated Thrombotic Microangiopathy
	Respiratory Complications
		Idiopathic Pneumonia Syndrome
		Cryptogenic Organizing Pneumonia
		Bronchiolitis Obliterans
		Secondary Solid Cancers
		Oral Cancer
		Skin Cancer
		Other Cancers
	Endocrine and Metabolic Complications
		Thyroid Complications
		Diabetes Mellitus
	Adrenal Complications
		Osteoporosis and Bone Complications
		Gonadal Dysfunction
			Fertility
	Renal Complications
	Hemorrhagic Cystitis
	Cardiac Complications
	Neurological Complications
		Posterior Reversible Encephalopathy Syndrome
		Progressive Multifocal Leukoencephalopathy
		Immune-Mediated Complications of Central and Peripheral Nervous System
		Complications Due to CNIs
	Gastrointestinal Complications
	Psychological Complications
25 - Prophylaxis and Management of Infectious Complications After Hematopoietic Cell Transplantation
	Background
	Preengraftment Risk Period
	Postengraftment Risk Period
		Early Risk Period
		Late Risk Period
	Management of Different Infections
		Neutropenic Fever Syndromes
		Growth Factors
		Granulocyte Transfusions
	Management of Fungal Infections
		Invasive Candidiasis
		Invasive Aspergillosis
		Mucormycosis
		Pneumocystis Jiroveci Pneumonia
	Management of Viral Infections
		Cytomegalovirus Infection
		CMV Infection and Disease
		Hemorrhagic Cystitis
		Human Herpesvirus 6
		Varicella Zoster Virus Infection
		Herpes Simplex Virus
		Ebstein-Barr Virus
		Respiratory Viral Infection
	Parasitic Infections
	Different Syndromes
		Pulmonary Complications
		Hepatitis
		Diarrhea
		Rash
	Donor-Driven Infections
	Long-Term Follow-up—Vaccination
26 - Hematopoietic Stem Cell Transplantation for Hematologic Malignancies in HIV-Positive Patients
	Introduction
	Epidemiology of HIV-Associated Lymphoma
		HIV-Associated Lymphoma
	ASCT in HIV Patients
	Allogeneic Stem Cell Transplantation in HIV Patients
	cART Management During HSCT
	HIV Reservoir
	Gene Therapy for Treatment of HIV-1
	Conclusions
27 - Symptom Control and Palliative Care in Hematopoietic Stem Cell Transplantation
	Introduction
	QOL Measures
	Graft-Versus-Host Disease
	Mucositis
		Incidence and Risk Factors
		Clinical Presentation and Course
		Prevention
		Treatment
	Nausea and Vomiting
		Chemotherapy-Induced Nausea
	Pain
		Mechanisms of Pain
		Pain Assessment
		Selecting a Pain Regimen
	Delirium
	Diarrhea
	Palliative Care in Hematopoietic Cell Transplantation
28 - Principles and Applications of Cellular Therapy in the Setting of Hematopoietic Cell Transplant
	Immunologic Status and Reconstitution After hematopoietic cell transplant
	Role of Cellular Therapy in Reducing Infectious Post-HCT Morbidity and Mortality
	Principles of Generating Virus-Specific T Lymphocytes (VSTs)
		Clinical Use of VSTs
	Role of Cellular Therapy in Controlling Graft-Versus-Host Disease
		Depletion of αβ (Alpha-Beta) T Cells
			Depletion of Antigen-Naïve T Cells
			Infusion of ‘Suicide Gene’-Transduced Donor Lymphocytes
			Infusion of Donor-Derived T-Regulatory Cells (Tregs)
			Photodepletion of Alloreactive T Cells
			Infusion of Mesenchymal Stem Cells (MSCs)
	Role of Cellular Therapy in Promoting Engraftment and Potentiating Graft-Versus-Tumor (GVT) Effect
		Unmodified Donor Lymphocyte Infusion (DLI)
		Adoptive Transfer of Tumor-specific Cytotoxic T Lymphocytes
		Adoptive Transfer of γδ (Gamma-Delta) T Cells
		Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy
			Development and optimization of CAR-T cell strategies
			Clinical results with CAR-T cells
			Outlook for CAR-T cell therapy
		Adoptive Transfer of Natural Killer (NK) Cells
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	Y