Hematopoietic Stem Cell Transplantation: A Handbook for Clinicians, 2nd Edition

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This second edition of Hematopoietic Stem Cell Transplantation: A Handbook for Clinicians (HSCT) offers comprehensive and practical information for healthcare providers working in the HSCT field. It provides relevant information on all areas of HSCT, including indications for transplantation; donor and patient evaluation; conditioning regimens; collection, processing, and characterization of stem cell products; management of immunosuppressive therapy; evaluation and management of the most common complications during HSCT; supportive care management; common procedures; and aspects of follow-up care. The emphasis of the Handbook is placed on providing up-to-date information in a clinically meaningful way.

This edition’s content has been reorganized to facilitate finding topics of interest more easily and the authors emphasized an educational bent in presenting their material. Each of the topics in the first edition has been revised to ensure the content is up to date. New chapters covering nonmalignant diseases, haploidentical transplants, photopheresis, financial considerations, and iron overload have been added.

Topics include:

- General Principles
- Pretransplant Concerns
- Donor Selection
- Graft Preparation
- Infusion and Support
- Outcomes
- Complications
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Preface to the First Edition
Preface to the Second Edition

1. Overview of Hematopoietic Stem Cell Transplantation
John R. Wingard, MD
I. Historical Perspective
II. A Primer of the Transplant Procedure
III. General Aspects About Different Types of HSCT
IV. What This Book Is About

2. Common Uses of Hematopoietic Stem Cell Transplantation
Joseph H. Antin, MD, and John R. Wingard, MD
I. Introduction
II. Marrow Failure
III. Hematologic Malignancies
IV. References/Suggested Readings

3. Hematopoietic Stem Cell Transplantation for Nonmalignant Disorders
Shalini Shenoy, MD
I. Introduction
II. Marrow Failure Syndromes
III. Metabolic Disorders
IV. Immune Deficiency/Dysfunction Disorders
V. Hemoglobinopathies
VI. Miscellaneous Rare Genetic Disorders
VII. Summary
VIII. References/Suggested Readings

4. Patient Evaluation Before Transplantation (Adult)
Jack W. Hsu, MD; Mehdi Hamadani, MD; and Steven M. Devine, MD
I. Introduction
II. Initial Consultation
III. Assessment of Disease Status
IV. Assessment of Physiologic Status
V. Psychological, Financial, and Caregiver Considerations
VI. References/Suggested Readings

5. Patient Evaluation Before Transplantation (Pediatric)
Nancy A. Kernan, MD
I. Overview
II. Assessment at Time of Referral
III. Assessment of Disease Status
IV. Assessment of Physiologic Function

6. Venous Access for Hematopoietic Stem Cell Transplantation Patients
James C. Andrews, MD, FSIR
I. General Principles
II. Options for Chronic Central Venous Access
III. Managing Central Venous Access Problems
IV. Summary
V. References/Suggested Readings

7. Conditioning Regimens
Javier Bolaños-Meade, MD, and Richard J. Jones, MD
I. Introduction
II. Common Myeloablative Regimens
III. Common Nonmyeloablative/RIC
IV. Toxicities
V. Antiemetic Management
VI. Selecting the Optimal Regimen
VII. References/Suggested Readings

8. Hematopoietic Progenitor Cell Donor Evaluation
John P. Miller, MD, PhD
I. Introduction
II. Types of Hematopoietic Progenitor Cell Donation
III. Medical Evaluation of HPC Donors
IV. Donor Consent for HPC Donation
V. Subsequent Donations
VI. Summary
VII. References/Suggested Readings

9. Optimal Donor Selection for Allogeneic Hematopoietic Stem Cell Transplantation
Aleksandr Lazaryan, MD, MPH, PhD, and Daniel J. Weisdorf, MD
I. Introduction
II. Related Donors
III. Adult Volunteer Unrelated Donors
IV. Umbilical Cord Blood
V. Summary
VI. References/Suggested Readings

10. HLA
Effie W. Petersdorf, MD
I. The Major Histocompatibility Complex
II. HLA Typing in Support of Allogeneic Transplant Programs
III. The Transplant Barrier
IV. References/Suggested Readings

11. HLA-Haploidentical Hematopoietic Stem Cell Transplantation
Christopher G. Kanakry, MD, and Ephraim J. Fuchs, MD, MBA
I. HLA Transplantation
II. Modern Approaches to HLA-Haploidentical Transplantation
III. T-Cell-Replete HLA-Haploidentical HSCT
IV. Reasons for Failure of HLA-Haploidentical HSCT
V. Conclusion
VI. References/Suggested Readings

12. Pediatric Aspects of Hematopoietic Stem Cell Transplantation
Kimberly A. Kasow, DO, and Gregory A. Hale, MD
I. Overview
II. Malignant Indications for Allogeneic Transplantation
III. Nonmalignant Indications for Transplantation
IV. Indications for Autologous Transplantation
V. Hematopoietic Stem Cell Sources
VI. Cellular Therapies
VII. Marrow Issues
VIII. Apheresis Issues
IX. Conditioning Regimen Issues
X. Pharmaceutical Aspects
XI. Acute and Chronic GVHD
XII. Supportive Care Issues
XIII. Prophylaxis
XIV. Late Effects
XV. References/Suggested Readings

Appendix 12-1. Drug and Radiation Doses for Pediatric HSCT

13. Stem Cell Grafts
Martin Körbling, MD, and Axel R. Zander, MD
I. Introduction
II. Biology of Cell Populations Contained in Hematopoietic
Tissue-Derived Stem Cell Grafts
III. Quantification of Graft-Containing Cells
IV. Engraftment Potential
V. Choice of Stem Cell Source in Adult Transplantation
VI. References/Suggested Readings

14. Stem Cell Collection Techniques
Ivana N.M. Micallef, MD, FRCP(C), and Dennis A. Gastineau, MD
I. Marrow Harvesting
II. Peripheral Blood Stem Cell Mobilization
III. Autologous Transplantation
IV. Allogeneic Transplantation
V. References/Suggested Readings

15. Cord Blood Graft Collection and Processing
Sue Armitage, BSc, and Elizabeth J. Shpall, MD
I. Overview
II. Types of Cord Blood Banking
III. Advantages of Cord Blood as a Source of
Hematopoietic Stem Cells
IV. Disadvantages of Cord Blood as a Source of
Hematopoietic Stem Cells
V. Cord Blood Banking Operations
VI. Registration of Units
VII. Clinical Results of Cord Blood Transplantation
VIII. References/Suggested Readings

16. Laboratory Processing of Hematopoietic Progenitor Cells
Dennis A. Gastineau, MD, and Douglas J. Padley, MT(ASCP)
I. Introduction
II. Manufacturing in the Cell Processing Laboratory
III. Plasma or Red Cell Incompatibility
IV. Donor Lymphocyte Infusion
V. HPC Product Testing
VI. Regulatory and Accreditation Issues and Process Control
VII. Other Products and Product Manufacturing
VIII. Administration of HPC Products
IX. References/Suggested Readings

17. Hematopoietic Progenitor Cell Administration
Christopher A. Tormey, MD, and Edward L. Snyder, MD
I. Introduction
II. Overview of HPC Components
III. Basics of HPC Administration
IV. ABO and Rh Incompatibility
V. Acute Adverse Events Associated with HPC
Administration: Complications and Management
VI. References/Suggested Readings

18. Engraftment
Paul V. O’Donnell, MD, PhD, FACP
I. Introduction
II. Factors Affecting Engraftment
III. Chimerism
IV. Erythroid Engraftment
V. Engraftment Following Allogeneic HSCT from
Alternative Donors
VI. Engraftment Syndrome
VII. References/Suggested Readings

19. Immune Reconstitution
Anthony D. Sung, MD; Yubin Kang, MD; and
Nelson J. Chao, MD, MBA
I. Overview of the Human Immune System
II. Assays for Monitoring Immune Reconstitution
III. Immune Reconstitution
IV. Immunomodulation and Immunoenhancement
V. Conclusion
VI. References/Suggested Readings

20. Transfusion Support for Hematopoietic Stem Cell Transplantation
Erin K.G. Meyer, DO, MPH, and Zbigniew M. Szczepiorkowski, MD, PhD, FCAP
I. Blood Component Collection and Testing
II. Blood Components—Types and Indications
III. Blood Components—Modifications
IV. Adverse Events Related to Transfusion of Blood Components
V. Transfusion Support for RBC-Incompatible Transplants
VI. Transfusion Support for the Pediatric HSCT Patient
VII. Therapeutic Apheresis
VIII. References/Suggested Readings

21. Hematopoietic Growth Factor Support After Hematopoietic Stem Cell Transplantation
Hong Yen Ng, Bsc (Pharm) (Hons), BCOP, and Yan Jiun Lim, Bsc (Pharm) (Hons), M Clin Pharm, BCOP
I. Red Cell Growth Factors
II. White Cell Growth Factors
III. Megakaryocytic Growth Factors
IV. References/Suggested Readings

22. Medical Nutrition Therapy in Hematopoietic Stem Cell Transplantation
Alison Winter-Lai, MS, RD, CSO, CDN, and
Courtney McGowan, MS, RD, CSO, CNSC, CDN
I. Nutrition Assessment Before Hematopoietic Stem
Cell Transplantation
II. HSCT and Energy/Protein Needs in Adults
III. HSCT and Energy/Protein Needs in Pediatrics
IV. Maintenance Fluid Needs
V. Vitamins/Minerals
VI. Eating Problems During and After HSCT
VII. Dietary Guidelines for Immunosuppressed Patients
VIII. Nutrition Support
IX. Long-term Nutrition Considerations Following HSCT
X. Summary
XI. References/Suggested Readings

23. Fluids and Electrolyte Management
Elizabeth C. DiMaggio, PharmD, BCOP
I. Fluctuations During Peripheral Blood Stem Cell (PBSC)
Apheresis
II. Influence of Drug Therapy Prior to HSCT
III. Electrolyte Abnormalities Following HSCT
IV. Fluid and Electrolyte Fluctuations from Supportive
Therapy Following HSCT
V. Electrolyte Disturbances at Engraftment
VI. References/Suggested Readings

24. Bacterial Infections
John R. Wingard, MD
I. Introduction
II. Risk Factors for Bacterial Infection
III. Neutropenic Fever
IV. Bacterial Infectious Syndromes
V. Prophylaxis
VI. References/Suggested Readings

25. Viral Infections After Engraftment
Helen Leather, BPharm, and Michael Boeckh, MD
I. Herpes Viruses
II. Respiratory Viruses
III. Adenoviruses
IV. Polyomaviruses
V. References/Suggested Readings

26. Fungal Infections
Shmuel Shoham, MD, and Kieren A. Marr, MD
I. Epidemiology and Pathogenesis
II. Prophylaxis
III. Specific Infections
IV. Summary
V. References/Suggested Readings

27. Infectious Hepatitis in Hematopoietic Stem Cell Transplantation
Richard A. Zuckerman, MD, MPH
I. Introduction
II. Pretransplant Evaluations
III. Hepatitis A Virus
IV. Hepatitis B Virus
V. Hepatitis C Virus
VI. Posttransplant Concerns
VII. Peritransplant Immunization
VIII. References/Suggested Readings

28. Posttransplant Vaccination Strategies
Ernesto Ayala, MD, and Claudio Anasetti, MD
I. Introduction
II. General Concepts
III. Vaccines Against Bacteria
IV. Vaccines Against Viruses
V. Serologic Testing
VI. Donor Vaccination
VII. Immunization of Family Members and Health-Care
Workers
VIII. References/Suggested Readings

29. Liver Disease After Hematopoietic Stem Cell Transplantation
Jan S. Moreb, MD
I. Introduction
II. Liver Problems During Pretransplant Evaluation
III. Drug-Induced Hepatobiliary Abnormalities
Following HSCT
IV. Nondrug-Related Liver Problems in the First 100 Days
V. Liver Abnormalities Beyond Day 100
VI. References/Suggested Readings

30. Oral Complications in Hematopoietic Stem Cell Transplantation
Nathaniel S. Treister, DMD, DMSC, and Stephen T. Sonis, DMD, DMSC
I. Introduction
II. Pre-HSCT Dental Evaluation
III. Approach to Diagnosis in the HSCT Recipient
IV. Oral Mucositis
V. Oral Infections
VI. Noninfectious Causes of Orofacial Pain
VII. Graft-vs-Host Disease
VIII. Second Malignancy
IX. References/Suggested Readings

31. Gastrointestinal Complications of Hematopoietic Stem Cell Transplantation
Judith Lees, BPharm, and Dorothy M. Keefe, MD
I. Introduction
II. Nausea and Vomiting
II. Delayed Nausea or Vomiting Prevention
III. Esophageal/Gastric Mucositis
IV. Small Intestinal/Colonic Mucositis and Diarrhea
V. Constipation
VI. References/Suggested Readings

32. Lung Injury Following Hematopoietic Stem Cell Transplantation
Kenneth R. Cooke, MD, and Gregory A. Yanik, MD
I. Introduction
II. Infectious Interstitial Pneumonias
III. Idiopathic Pneumonia Syndrome
IV. Chronic Pulmonary Dysfunction After HSCT
V. Conclusion
VI. References/Suggested Readings

33. Management of Pain in the Hematopoietic Stem Cell Transplantation Patient
Laura E. Wiggins, PharmD, BCOP
I. Overview
II. Pathophysiology of Pain
III. Types of Pain in the HSCT Patient
IV. Diagnosis of Pain
IV. Management of Pain
V. Summary
VI. References/Suggested Readings

34. Hemorrhagic Cystitis
Zuzana Potácová, MD, PhD; Tina Dalianis, MD, PhD; Katarina Le Blanc, MD, PhD; and Olle Ringdén, MD, PhD
I. Overview
II. Pathogenesis and Role of Infection
III. Management
IV. References/Suggested Readings

35. Management of Coagulopathies/Transplant-Associated Microangiopathy
Yan Yun Wu, MD, PhD, and Peter W. Marks, MD, PhD
I. Hemorrhagic Complications
II. Thrombotic Complications
III. References/Suggested Readings

36. Anticoagulation, Thrombosis, and Bleeding in the Hematopoietic Stem Cell Transplantation Patient
Marc S. Zumberg, MD, and Molly Mandernach, MD, MPH
I. Introduction
II. Bleeding Complications After HSCT
III. Thrombotic Complications After HSCT
IV. Balancing the Risks of Bleeding vs the Benefits of
Anticoagulation
V. Anticoagulant Choice During HSCT
VI. References/Suggested Readings

37. Hyperlipidemia After Allogeneic Hematopoietic Stem Cell Transplantation
Bradley W. Blaser, MD, PhD; Vincent T. Ho, MD; and
Robert J. Soiffer, MD
I. Management of Hyperlipidemia Before Engraftment
II. Management of Hyperlipidemia After Engraftment
III. References/Suggested Readings

38. Neurologic Complications in Hematopoietic Stem Cell
Transplantation
Maxim Norkin, MD, PhD
I. Introduction
II. Neurologic Complications During the Pretransplant Period
III. Neurologic Complications During Preengraftment
IV. Neurologic Complications After Reconstitution of
Marrow Function
V. References/Suggested Reading

39. Acute GVHD
Corey Cutler, MD, MPH, FRCP(C)
I. Acute GVHD Pathobiology and Risk Factors
II. GVHD Prophylaxis
III. Diagnosis, Epidemiology, and Clinical Manifestations of Acute GVHD
IV. Treatment and Outcome of Acute GVHD
V. Survival After Acute GVHD
VI. References/Suggested Readings

40. Chronic GVHD
Iskra Pusic, MD; Georgia B. Vogelsang, MD; and Steven Z. Pavletic, MD
I. Pathophysiology of Chronic GVHD
II. Risk Factors
III. Diagnosis
IV. Classification
V. Staging
VI. Clinical Manifestations
VII. GVT Effect
VIII. Prevention
IX. Treatment
X. Measuring the Response to Therapy
XI. Monitoring Patients with Chronic GVHD
XII. Prognosis of Chronic GVHD
XIII. References/Suggested Readings

41. Photopheresis
Joseph G. Sokhn, MD; Jaehyuk Choi, MD, PhD; and
Francine M. Foss, MD
I. Introduction
II. Collection Techniques
III. UVA Irradiation
IV. Mechanisms of ECP
V. Therapeutic Applications of Photopheresis
VI. Clinical Efficacy of ECP for Treatment of GVHD
VII. Summary
VIII. References/Suggested Readings

42. Late Complications: Screening and Management
Navneet S. Majhail, MD, MS, and J. Douglas Rizzo, MD, MS
I. Overview
II. Guidelines for Screening/Prevention of Late Complications
III. Neuropsychiatric Complications
IV. Ocular Complications
V. Oral Complications
VI. Respiratory Complications
VII. Cardiac and Vascular Complications
VIII. Liver Complications
IX. Renal and Genitourinary Complications
X. Complications of Muscle and Connective Tissue
XI. Skeletal Complications
XII. Nervous System Complications
XIII. Endocrine Complications
XIV. Mucocutaneous Complications
XV. Fertility
XVI. General Preventive Health
XVII. References/Suggested Readings

43. Neuropsychiatric Complications of Hematopoietic Stem Cell Transplantation
Mitchell R. Levy, MD, and Jesse R. Fann, MD, MPH
I. General Principles of Assessment and Management
II. Level of Distress
III. Severe Neuropsychiatric Complications
IV. Cancer-Related Fatigue
V. Somatization
VI. Survivorship
VII. References/Suggested Readings

44. Psychosocial Sequelae of Hematopoietic Stem Cell Transplantation in Survivors and Caregivers
Michelle M. Bishop, PhD
I. Introduction
II. Major Psychosocial Sequelae After HSCT
III. Family Caregivers
IV. References/Suggested Readings

45. Second Cancers
Smita Bhatia, MD, MPH
I. Overview
II. Therapy-Related Myelodysplasia and Acute Myeloid
Leukemia After Autologous HSCT
III. Donor-Derived Hematologic Malignancies After HSCT
IV. Lymphomas
V. Solid Tumors
VI. Conclusions
VII. References/Suggested Readings

46. Relapse After Hematopoietic Stem Cell Transplantation
Michael R. Bishop, MD
I. Introduction
II. Biology
III. Relapse Risk
IV. Monitoring
V. Prevention of Relapse
VI. Treatment of Relapse
VII. Summary
VIII. References/Suggested Readings

47. Donor Lymphocyte Infusion and Graft-vs-Leukemia Effects of Allogeneic Transplantation
Hans-Jochem Kolb, MD, and Raymund Buhmann, MD
I. Separation of GVL Effects and Graft-vs-Host Disease
II. CML
III. DLI in AML and MDS
IV. DLI in ALL
V. DLI in Chronic Lymphocytic Leukemia and Lymphoma
VI. DLI in Multiple Myeloma
VII. DLI in Solid Tumors
VIII. Immunotherapy in Patients with HLA-Haploidentical Donors
IX. Treatment of Viral Infections with Donor Lymphocytes
X. Do Donor Lymphocytes Eliminate Leukemia Stem Cells?
XI. Failure of Durable Control–Immune Escape Mechanisms
XII. Future of DLI
XIII. Acknowledgments
XIV. References/Suggested Readings

48. Gynecologic Management of Fertility
Sanaz Ghazal, MD; Jason G. Bromer, MD; and
Pasquale Patrizio, MD, MBE
I. Introduction
II. The Effect of Gonadotoxic Agents on Fertility
III. Established Strategies for Fertility Preservation
IV. Experimental Strategies for Fertility Preservation
V. Strategies for Ovarian Protection
VI. Ethical Considerations in Fertility Preservation
VII. Summary and Conclusions
VIII. References/Suggested Readings

49. Pathogenesis, Diagnosis, and Management of Iron Overload in Hematopoietic Stem Cell Transplantation
Maxim Norkin, MD, PhD, and Ashley Richards, PharmD, BCOP
I. Introduction
II. Basic Principles of Iron Homeostasis and
Pathophysiology of IO in HSCT Recipients
III. Assessment and Monitoring of IO and Body Iron Burden
IV. Prevalence of IO in HSCT Recipients
V. Impact of IO on Clinical Outcomes in HSCT Recipients
VI. Iron Reduction Therapy in HSCT Recipients
VII. Screening for IO After HSCT
VIII. Monitoring the Response to IRT
IX. Summary and Future Developments
X. References/Suggested Readings

50. Dosing Considerations in Overweight and Obese Patients Receiving High-Dose Chemotherapy and Hematopoietic Stem Cell Transplantation
Dennis L. Cooper, MD
I. Overview
II. Dosing for Overweight Patients
III. References/Suggested Readings

51. Common Procedures in Hematopoietic Stem Cell Transplantation
Bimalangshu R. Dey, MD, PhD, and Thomas R. Spitzer, MD
I. Introduction
II. Marrow Aspiration and Biopsy
III. Skin Biopsy
IV. Lumbar Puncture
V. Marrow Harvest
VI. Apheresis
VII. References/Suggested Readings

52. Data Collection and Management for Hematopoietic Stem Cell Transplantation Centers
Wael Saber, MD, MS, and Mary M. Horowitz, MD, MS
I. Introduction—Why Collect Data?
II. Data Collection at the Transplant Center—Ensuring
Quality and Addressing Local Research Needs
III. Outcomes Registries—Contributing to the National and International
Research Enterprise
IV. Addressing Federal Requirements—the US SCTOD
V. Summary
VI. References/Suggested Readings

53. Accreditation Standards and Quality Programs in Hematopoietic Stem Cell Transplantation
Michele W. Sugrue, MS, MT(ASCP)SBB;
Zbigniew M. Szczepiorkowski, MD, PhD; and Dennis A. Gastineau, MD
I. Quality Management Systems in Clinical Practice
II. Change Control
III. The Quality Committee
IV. Interruption of Services
V. Accreditation and Standards
VI. United States Food and Drug Administration (FDA)
Regulations and Oversight
VII. Conclusion
VIII. References/Suggested Readings

54. Financial Aspects of Hematopoietic Stem Cell Transplantation
Richard T. Maziarz, MD; Jeffrey W. Chell, MD; and
Richard E. Champlin, MD
I. Introduction
II. Increase in Utilization and Impact of HSCT on National
Health-Care Costs
III. Complexity of Care Increases Costs
IV. Payer Source
V. Contracts and Reimbursement Strategies
VI. Resource Utilization
VII. Research
VIII. Quality
IX. Future Considerations
X. Summary
XI. References/Suggested Readings

Appendices
Appendix 1. Antibacterial Adult Dosage Guidelines for Patients with Normal Renal Function and Renal
Insufficiency (As of January 2013)
Appendix 2. Antifungal Adult Dosage Guidelines for Patients with Normal Renal Function and Renal Insufficiency (As of January 2013)
Appendix 3. Antiviral Adult Dosage Guidelines for Renal Insufficiency (as of January 2013)
Appendix 4. Drug Interactions with Antifungal Agents Cytochrome P450 Isoenzymes Involved in Drug Metabolism
Appendix 5. Clinically Relevant Pharmacokinetic Drug Interactions with Ketoconazole
Appendix 6. Clinically Relevant Pharmacokinetic Drug Interactions with Fluconazole
Appendix 7. Clinically Relevant Pharmacokinetic Drug Interactions with Itraconazole
Appendix 8. Clinically Relevant Pharmacokinetic Drug Interactions with Variconazole: Effect of Voriconazole on the Pharmacokinetis of Other Drugs
Appendix 9. Clinically Relevant Pharmacokinetic Drug Interactions with Voriconazole: Effect of Other Drugs on the Pharmacokinetics of Voriconazole
Appendix 10. Drug Interactions with Posaconazole
Appendix 11. Clinically Relevant Pharmacokinetic Drug Interactions with Tacrolimus
Appendix 12. Clinically Relevant Pharmacokinetic Drug Interactions with Cyclosporine
Appendix 13. Clinically Relevant Pharmacokinetic Drug Interactions with Sirolimus
Appendix 14. Cyclosporine Dosing and Monitoring Guidelines
Appendix 15. Tacrolimus Dosing and Monitoring Guidelines

Index

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