Pulmonary and Critical Care Considerations of Hematopoietic Stem Cell Transplantation

Foreword I
Foreword II
Preface
Contents
Editor and Contributors
About the Editor
Contributors
1: Hematopoietic Stem Cell Transplantation: An Overview
Introduction
Autologous Stem Cell Transplant
Collection of Stem Cells
Risk Factors of Poor Mobilization
Conditioning Regimen
Allogeneic Stem Cell Transplant
Donor Selection for Allogeneic HSCT
Sources of Hematopoietic Stem Cells
Bone Marrow
Peripheral Blood
Umbilical Cord Blood (UCB)
Conditioning Regimen
Complications of Stem Cell Transplantation
Early Complications
Graft-Versus-Host Disease (GVHD)
Infectious Diseases
Pre-engraftment: From HSCT to Engraftment (Day 0 to +30)
Early Post-engraftment: Day +30–100
Late Post-engraftment: Beyond Day +100
Oral Mucositis
Hemorrhagic Cystitis
Sinusoidal Obstruction Syndrome (SOS)
Transplant-Associated Microangiopathy (TMA)
Late Complications
References
2: An Overview of Graft-Versus-Host Disease
Introduction
Pathophysiology of GVHD
GVHD: Incidence and Impact on Non-relapse Mortality (NRM)
Risk Factors of GVHD
Classification of GVHD
Staging and Grading of Acute GVHD
Staging/Grading of Chronic GVHD
Introduction of the Concept of GVHD Prophylaxis
Introduction of Cyclosporine A for GVHD Prophylaxis
Use of Combination Drugs for GVHD Prophylaxis
Trials Assessing Tacrolimus Versus CsA
Mycophenolate Mofetil (MMF)
Antithymocyte Globulin (ATG) for In Vivo T-Cell Depletion
Posttransplantation Cyclophosphamide (PTCy)
Sirolimus
Ex Vivo T-Cell Depletion for GVHD Prophylaxis
Targeting T-Cell Co-stimulatory Receptors
Treatment of GVHD
Pulmonary Perspectives
References
3: Pulmonary Complications Following Hematopoietic Stem Cell Transplantation: Spectrum, Incidence, Risk Factors, and Outcomes
Introduction
Infectious Complications
Bacterial Complications
Pneumonia
Nocardia
Mycobacterium tuberculosis (MTB)
Nontuberculous Mycobacterial Infections
Viral Complications
Cytomegalovirus
Respiratory Virus Infections (RVI)
SARS-CoV-2
Invasive Fungal Infections
Noninfectious Complications
Idiopathic Pneumonia Syndrome (IPS)
Peri-Engraftment Respiratory Distress Syndrome (PERDS)
Diffuse Alveolar Hemorrhage (DAH)
Cryptogenic Organizing Pneumonia (COP)
Bronchiolitis Obliterans Syndrome (BOS)
Interstitial Lung Disease (ILD)
Pulmonary Hypertension and Pulmonary Veno-Occlusive Disease (PVOD)
Thoracic Air Leak Syndrome (TALS)
Pleural Effusions
Venous Thromboembolic Disease (VTE) and Pulmonary Cytolytic Thrombi (PCT)
Other Noninfectious Complications
Acute Respiratory Failure and Mechanical Ventilation
Diagnostic Considerations of Noninfectious Pulmonary Complications Following HSCT
Conclusion
References
4: Pretransplant Pulmonary Evaluation
Introduction
Pulmonary Function Tests Overview
Spirometry
Lung Volumes
Diffusing Capacity
Role of PFTs in the Pre-HSCT Pulmonary Evaluation
Consideration of Type of Conditioning
Prediction of Respiratory Failure and Mortality
Prediction of Airflow Obstruction and Bronchiolitis Obliterans Syndrome
Prediction of Non-pulmonary Complications
Role of Other Tests in the Pre-HSCT Risk Assessment
Arterial Blood Gas (ABG)
Chest Imaging
Assessment of Cardiopulmonary Fitness
Risk Mitigation
Restrictive Impairment
Obstructive Lung Disease
Smoking Cessation
Reducing the Risk of Respiratory Infection
Conclusions
References
5: Diagnostic Evaluation of Pulmonary Disease Following Hematopoietic Stem Cell Transplantation
Diagnosis Evaluation: Overview
Diagnosis Evaluation: Specifics
Bacterial Pneumonias
Mycobacteria
Viral Pneumonias
Fungal Pneumonias
Parasitic Infections
Radiation and Drug-Induced Toxicity
Aspiration Pneumonitis
Cardiogenic Pulmonary Edema
Diffuse Alveolar Hemorrhage
Acute Respiratory Distress Syndrome
Organizing Pneumonia
Engraftment Syndrome
Idiopathic Pneumonia Syndrome
Graft-Versus-Host Disease
Malignancy
Connective Tissue Disease, Vasculitis
Pulmonary Alveolar Proteinosis
Pulmonary Vascular Disease
References
6: Pulmonary Complications Following Hematopoietic Stem Cell Transplantation: Radiological Considerations
Infectious Complications
Bacterial Infections
Fungal Infections
Viral Infection
Noninfectious Complications
Chronic Graft-Versus-Host Disease (cGVHD)
Other Noninfectious Pulmonary Complications
Conclusion
References
7: Bacterial Pneumonia in Hematopoietic Stem Cell Transplant Recipients
Overview
Temporal Considerations in HSCT-Related Bacterial Pneumonia
Imaging of Patients with Suspected Bacterial Pneumonia
Laboratory Testing for Suspected Bacterial Pneumonia
Management of Bacterial Pneumonia in HSCT Patients
Host-Targeted Therapies
Summary
References
8: Invasive Pulmonary Aspergillosis in Hematopoietic Stem Cell Transplantation
Introduction
Mycology
Immunopathogenesis
Epidemiology and Risk Factors
Clinical Features
Diagnosis
Antifungal Resistance
Management
Prevention
Future Directions
References
9: Other Respiratory Fungal Infections
Introduction
Fusarium Infections
Pathogenesis
Clinical Aspects
Diagnosis
Treatment
Scedosporium and Lomentospora Infections
Pathogenesis
Clinical Aspects
Diagnosis
Treatment
Mucormycosis
Pathogenesis
Clinical Aspects
Diagnosis
Treatment
Pneumocystis Infection
Pathogenesis
Clinical Aspects
Diagnosis
Treatment
References
10: Cytomegalovirus Diseases in Hematopoietic Cell Transplant Recipients
Introduction: General Principles
Pathophysiology of CMV
Risk Factors for CMV Reactivation and Disease
Transplant-Related Factors
Host-Related Risk Factors
Laboratory Studies and Novel Tools
Prevention
CMV Infection or Reactivation: Diagnosis and Treatment
CMV Disease: Presentation, Diagnosis, and Therapy
CMV Pneumonia
CMV Gastrointestinal Disease
CMV Retinitis
CMV Central Nervous System Disease/Encephalitis
Other CMV Disease Manifestations
Resistant and Refractory CMV Infection and Disease
Definitions
Mechanisms of CMV Resistance
Management of Resistant/Refractory CMV
Other Agents and Novel Therapies
Conclusion
References
11: Respiratory Viral Infections
Introduction
Diagnostic Considerations
Specific Viral Infections
Influenza Viruses
Adenoviruses
Respiratory Syncytial Virus (RSV)
Human Metapneumovirus (HMPV)
Parainfluenza Virus (PIV)
Human Rhinovirus
Human Coronaviruses Other Than SARS-CoV-2 (HCoVs)
Special Considerations for HCT Recipients with Respiratory Viruses
Pretransplant Respiratory Viral Infections
Clinical Sequelae of Respiratory Viral Illness
Adjunct Corticosteroids and Other Immunosuppressive Agents
Summary and Future Directions
References
12: COVID-19 and Hematopoietic Stem Cell Transplantation
Incidence and Pathophysiology
Clinical Presentation and Risk Factors
Management and Therapeutic Treatments for COVID-19
EBMT Recommendations
ASH: ASTCT Recommendations
Vaccination
Conclusions and Future Directions
References
13: Sepsis and Septic Shock: Special Considerations in the Hematopoietic Stem Cell Transplantation Patient
Introduction
Definition and Screening for Sepsis
Initial Resuscitation and Fluid Management
Vasopressors
Antimicrobial Treatment and Source Control
Mechanical Ventilation
Additional Therapies
Conclusion
References
14: Diffuse Alveolar Hemorrhage in Hematopoietic Stem Cell Transplantation
Introduction
Definition and Diagnosis
Clinical Presentation and Time Course
Incidence
Risk Factors
Pathogenesis
Management and Treatment
Prognosis
Research and Conclusions
References
15: Engraftment Syndrome and Peri-engraftment Respiratory Distress
Introduction
Definition of ES
Distinction of ES from Other Cytokine-Mediated Syndromes After HSCT
Mechanism of the Pulmonary Manifestations of ES
Pulmonary Manifestations of ES
Differential Diagnosis of Pulmonary ES
Infection
Diffuse Alveolar Hemorrhage (DAH)
Heart Failure
GVHD
Drug-Induced Pneumonitis
Idiopathic Pneumonia Syndrome (IPS)
Diagnostic Evaluation
Treatment of ES
Conclusions and Future Direction
References
16: Idiopathic Pneumonia Syndrome
Introduction
Incidence
Risk Factors
Conditioning Regimen
Acute Graft-Versus-Host Disease
Infections
Pretransplant Pulmonary Function
Pathophysiology
Clinical Presentation and Diagnostic Criteria
DAH and PERDS
Management
Corticosteroids
Antibiotics
Etanercept
Adjunctive Therapies: DAH
Lung Transplantation
Outcomes
Conclusion
References
17: Bronchiolitis Obliterans Syndrome
Introduction
Epidemiology
Pathophysiology
Risk Factors
Diagnostic Criteria
Management and Outcome
Treatment
BOS Prophylaxis
Conclusion
References
18: Late-Onset Interstitial Lung Disease Following Allogeneic Hematopoietic Stem Cell Transplantation
Introduction
Epidemiology
Pathophysiology
Spectrum of Post-HSCT Interstitial Lung Diseases
Organizing Pneumonia
Pleuroparenchymal Fibroelastosis
Other Noninfectious ILDs
Risk Factors
Diagnostic Criteria
Management and Outcome
Conclusion
References
19: Other Noninfectious Pulmonary Complications
Introduction
Pleural Effusions
Venous Thromboembolic Disease
VTE Prophylaxis and Treatment
Pulmonary Hypertension
Post-transplant Lymphoproliferative Disorder (PTLPD)
Solid Malignancies
Pulmonary Alveolar Proteinosis (PAP)
Thoracic Air-Leak Syndrome
References
20: Pulmonary Rehabilitation in Hematopoietic Stem Cell Transplantation Patients
Introduction
Respiratory and Physical Functions of HSCT Patients
The Pre-HSCT Phase
The Peri-and Early Post-HSCT Phases
The Late Post-HSCT Phase
Rehabilitation of HSCT Patients
Exercise Therapy for Patients with HSCT
Respiratory Muscle Training for HSCT Patients
Respiratory Rehabilitation of HSCT Patients with Pulmonary Complications
Conclusions
References
21: Pulmonary Complications of Common Hematopoietic Stem Cell Transplantation Therapies
Introduction
Mechanisms of Toxicity
Conditioning Agents
Busulfan
Carmustine
Cyclophosphamide
Fludarabine
Cytarabine
Etoposide
Melphalan
Total Body Irradiation
Granulocyte Colony-Stimulating Factor
Medications Used in the Treatment of Graft-Versus-Host Disease
Calcineurin Inhibitors
Rituximab
Ruxolitinib
Sirolimus
Ibrutinib
Belumosudil
Conclusion
References
22: Sleep Disturbances in Hematopoietic Stem Cell Transplantation
Introduction
Sleep Disorders and Cancer
Insomnia
Sleep-Related Breathing Disorders
Movement Disorders
Circadian Rhythm Disorder
Cancer-Related Fatigue (CRF)
Symptom Clusters
Sleep Disturbances Before, During, and After HSCT
Acute Transplant Period
Post-transplant
Special Considerations
Conclusion
References
Untitled
23: Lung Transplantation for Hematopoietic Stem Cell Transplant Patients
Lung Transplantation After Hematopoietic Stem Cell Transplantation
Lung Transplant Referral, Evaluation, and Timing of Transplant
Post-transplant Considerations
Perioperative Issues
Immunosuppression
Prophylaxis
Infections
Acute Rejection
Chronic Lung Allograft Dysfunction
Malignancy
Mortality
Health-Related Quality of Life
Patients with Primary Immunodeficiency
Conclusion
References
24: Outcomes in Critically Ill Allogeneic Hematopoietic Stem Cell Transplantation Recipients
Introduction
Intensive Care Unit Admission
Risk Factors for ICU Admission
Timing of Intensive Care Unit Admission
Indications of Intensive Care Unit Admission
Autologous and Allogeneic HSCT Induce Different Patterns of Organ Dysfunction
The Number of Organ Dysfunction Is the Major Determinant of Mortality
The Assessment of Acute GVHD (aGVHD) Trajectory Might Help to Identify Allo-HSCT Patients Who Could Benefit from Critical Care
Early ICU Admission of Allo-HSCT Recipients Is Associated with Better Outcomes
Need for Precision and Personalized Critical Care Management of Allo-HSCT Recipients
Long-Term Survival of Allo-HSCT Recipients Is Encouraging and No Longer Affected by a Former ICU Stay
Conclusion
References
25: Respiratory Support of the Critically Ill Hematopoietic Stem Cell Transplant Patient
Introduction
Features of Pulmonary Complications Following HSCT
Noninvasive and Invasive Respiratory Support
Noninvasive Respiratory Support
Non-immunocompromised Patient Population
Immunocompromised Patient Population
Placing Research into Context for the HSCT Patient Population
Future Role of Noninvasive Respiratory Support
Palliative Use of Noninvasive Respiratory Support
Invasive Mechanical Ventilation
Severe ARDS Adjunctive Measures and Extracorporeal Life Support (ECLS)
Conclusion
References
26: Cardiovascular Considerations in Patients Undergoing Hematopoietic Stem Cell Transplantation
Incidence and Risk Factors of Acute and Long-Term Cardiac Complications
Incidence of Acute Complications
Incidence of Long-Term Complications
Risk Factors for Cardiovascular Complications
Patient Factors
Disease-Related Factors
Prior Cancer Therapy
Mechanisms of Cardiovascular Complications
Role of the Cardio-oncology Team
The Pre-HSCT Cardiovascular Assessment
History and Physical Exam
Risk Models
Cardiac Structure and Function
Assessing for Ischemia
Pre-HSCT Management of Cardiovascular Comorbidities
Special Considerations for Inpatient Management of Cardiovascular Complications
Survivorship
Conclusion
References
27: Renal Considerations in Critically Ill Hematopoietic Stem Cell Transplant Patients
Introduction
Epidemiology of AKI in HSCT
Outcomes of Post-HSCT AKI
Predictors of AKI
Pathogenesis of AKI in Critically Ill Patients After HSCT
Prerenal and Cytokine Release Syndromes
Sepsis
Hepatic Sinusoidal Obstruction Syndrome (SOS)
Engraftment Syndrome
Complement- and Immune-Related AKI
Graft-Versus-Host Disease
Transplant-Associated Thrombotic Microangiopathy
Acute Glomerulonephritis
Transplant- or Tumor-Related AKI
Marrow Infusion Syndrome
Tumor Lysis Syndrome
Viral Infections
Nephrotoxins in HSCT
Calcineurin Inhibitors
Antimicrobials
Conditioning Regimen
Diagnosis
Biomarkers
Role of Kidney Biopsy
Management of Post-HSCT AKI
Monitoring and Prevention
Treatment
General Measures
Kidney Replacement Therapy Considerations
Disease-Specific Considerations
Hepatic Sinusoidal Obstruction Syndrome
Transplant-Associated Thrombotic Microangiopathy
Viral Infections
Conclusion
References
28: Gastrointestinal and Hepatic Considerations in Critically Ill Hematopoietic Stem Cell Transplantation Patient
Introduction
Patient’s Assessment
Allogeneic HSCT
Early HSCT Period (Up to Day 100)
Pain
Diarrhea
Neutropenic Enterocolitis
Acute Graft-Versus-Host Disease (GVHD)
Jaundice
Late HSCT Period (Day 100+)
Chronic GVHD
Iron Overload
Autologous HSCT
References
29: Neurologic Considerations in Critically Ill Hematopoietic Stem Cell Transplantation Patients
Introduction
Drug-Related Neurotoxicity
Calcineurin Inhibitors
Cytotoxic Agents
Monoclonal Antibodies
Antimicrobials
Metabolic Encephalopathy
Wernicke’s Encephalopathy
Cerebrovascular Disease
Infectious Complications
Fungal Infections
Toxoplasmosis
Viral Infections
Progressive Multifocal Leukoencephalopathy
Bacterial Infections
Immune-Mediated Complications
Acute Immune-Mediated Polyneuropathy (Guillain-Barré Syndrome)
Neurological Manifestations of Chronic Graft-Versus-Host Disease
Immune Reconstitution Inflammatory Syndrome (IRIS)
Cytokine Release Syndrome
Neuro-diagnostics
References
30: Hematological Considerations in Critically Ill Hematopoietic Stem Cell Transplantation Patients
Introduction
Laboratory Analysis and Venous Access
Transfusion Support
Packed Red Blood Cell Transfusion
Platelet Transfusion
Platelet Refractoriness
Fresh Frozen Plasma and Cryoprecipitate
Granulocyte Colony-Stimulating Factors
Delayed Engraftment/Graft Failure
Hemolytic Anemia and Pure Red Cell Aplasia
Transplant-Associated Thrombotic Microangiopathy
Secondary Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome
Conclusion
References
31: Pulmonary and Critical Care Considerations in Pediatric Hematopoietic Stem Cell Transplantation Patient
Introduction
Pulmonary Dysfunction Following Pediatric HSCT
Overview
Clinical Phenotypes
Risk Factors
Diagnostic Challenges Unique to Pediatric HSCT Patients
Mechanisms of Lung Injury Following HSCT
Treatment of Pulmonary Complications in Pediatric HSCT Patients
Transplant-Associated Microangiopathy (TA-TMA)
Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS)
Critical Care Considerations for Pediatric HSCT Recipients
Conclusion
References
32: CAR T-Cell Therapy and Critical Care Considerations
Introduction
Overview of CAR Therapy
Types of CAR, Indications and FDA Approval
Cell Preparation, Apheresis, Lymphodepletion and Cell Infusion
Institutional Considerations
Acute Complications Post-Infusion
Cytokine Release Syndrome
Immune Effector Cell-Associated Neurotoxicity Syndrome
Hemophagocytic Lymphohistiocytosis
Infectious Complications
Other Reasons for ICU Admission, Considerations and Resource Utilization
Long-Term Complications and Considerations Post CAR T-Cell Therapy
Prolonged Cytopenias, Haematopoietic Failure and B-Cell Aplasia
Infectious Considerations and Prophylaxis
Role of Haematopoietic Stem Cell Transplant After CAR Therapy
Conclusion
References
33: Critical Care Nursing of Haematopoietic Stem Cell Transplantation Patients
Introduction
Haematopoietic Stem Cell Transplantation
ICU Admission of HSCT Patients
Collaboration Between Transplant and ICU HCPs
Multidirectional Learning Process
Nursing Management of HSCT Patients
Nursing Management of HSCT Patients in the ICU
The ABCDEF Bundle at the Bedside of the HSCT Patient: Implications for Nursing
Assess, Prevent and Manage Pain
Both Spontaneous Awakening Trials (SAT) and Spontaneous Breathing Trials (SBT)
Choice of Analgesia and Sedation
Delirium Assessment, Prevention and Management
Early Mobility and Exercise
Family Engagement and Empowerment
References
34: Nutritional Considerations of Critically Ill Hematopoietic Cell Transplantation Patients
Introduction
Nutritional Issues in Allogeneic HCT Recipients in General
Nutritional Support in Critically Ill HSCT Recipients
Assessment of Nutritional Status
Target Caloric Intake
Route of Nutritional Support
Special Considerations in Patients After Allogeneic HCT
Conclusion
References
Untitled
35: Critically Ill Hematopoietic Stem Cell Transplantation Patient: Provider Burnout and Support
Introduction
Background
HSCT and Provider Burnout
Signs and Symptoms
Interventions
Impact of COVID-19 on HSCT Providers
Implications
References
36: Multidisciplinary Care and ICU Organization for Hematopoietic Stem Cell Transplantation Patients
Introduction
Multidisciplinary Care
ICU Providers
Intensivists
Hematologists/Oncologists
Advanced Practice Providers
Nursing
Respiratory Therapists
Pharmacists
Nutritionists/Dieticians
Physical and Occupational Therapists
Consultants
Intensive Care Unit Organization
Unit Model
Physical Plant Considerations
Unit Leadership
Quality Assurance and Outcome Metrics
Conclusion
References
37: Long Term Survivors of Hematopoietic Stem Cell Transplantation: The Role of the Pulmonologist
Introduction
The Historical Context
The Burden of Late-Onset Lung Disease
Models of Long-Term Care
Early Diagnosis of BOS After HSCT
Treatment of BOS After HSCT
Quality of Life and End of Life
Pediatric Considerations
Education, Training, and Research
Summary
References
Index