Post-Transplant Lymphoproliferative Disorders (eBook)

Dedication 5
Foreword 6
Contents 8
Contributors 10
Chapter 1 12
Introduction 12
References 14
Chapter 2 15
Historical Perspective on the Early Studies of Posttransplant Lymphoproliferative Disorders (PTLD) 15
2.1 Malignancies in Immunocompromised Hosts 15
2.2 The Epstein–Barr Virus 16
2.3 The Serendipitous Intersection of Immunosuppression and EBV 16
2.4 Initial Studies of “Posttransplant Lymphoma” 17
2.5 Growing Experience with EBV and Posttransplant Lymphoproliferative Diseases 17
2.6 Clinical Spectrum of Lymphoproliferative Disorders 18
2.7 Morphology 18
2.8 Clonality 19
2.9 EBV 20
2.10 Therapy 20
2.11 Summary Classification of PTLD 21
2.12 Pathogenesis 22
2.13 Conclusions 23
2.14 Take Home Pearls 23
References 23
Chapter 3 26
Epidemiology of PTLD 26
3.1 Introduction 26
3.2 Incidence of PTLD 26
3.3 Time to PTLD 28
3.4 Risk Factors for PTLD 28
3.4.1 Infection Related Risk Factors 28
3.4.2 Host-Related Risk Factors 29
3.4.3 Primary Disease Related Factors 30
3.4.4 Graft Organ Related Risk Factors 30
3.4.5 Immunosuppression Related Risk Factors 32
3.5 Mortality After PTLD 33
3.6 Risk for Graft Loss After PTLD 33
3.7 Re-Transplantation After PTLD in Prior Transplant 33
3.8 Take Home Messages 34
References 34
Chapter 4 38
The Biology of Epstein–Barr Virus and Posttransplant Lymphoproliferative Disease 38
4.1 Introduction 38
4.2 Biology of EBV 39
4.2.1 Infection 39
4.2.2 The Viral Life Cycle 39
4.2.3 Latent Cycle Genes of EBV 41
4.2.4 Characteristics of the T Cell Response to EBV in Healthy Individuals 43
4.2.5 Characteristics of the T Cell Response to EBV in Transplant Recipients 44
4.3 PTLD 45
4.3.1 Viral Determinants that Drive Growth and Survival of PTLD-Associated B Cell Lymphomas 47
4.3.2 Viral Mechanisms of Immune Evasion or Subversion 47
4.3.3 Direct Eff ects of Immunosuppression on Viral Infection and Tumor Cell Growth 48
4.4 Conclusion 49
4.5 Take Home Pearls 49
References 49
Chapter 5 53
Epstein–Barr Viral Load Testing: Role in the Prevention, Diagnosis and Management of Posttransplant Lymphoproliferative Disorders 53
5.1 Introduction 54
5.2 EBV VL Assessments-What Is Being Measured? 54
5.3 Limitations and Unresolved Issues Related to EBV VL Assays 56
5.4 Lack of Standardization and Cross-Referencing of Assays 56
5.5 Specimen Type and Reporting Units 57
5.6 The Use of EBV VL Assessments for Specifi c Clinical Purposes 59
5.6.1 EBV VL Assessments for Preemptive Programs Targeting PTLD Prevention 59
5.6.2 Laboratory Tests as Adjuncts to EBV VL Assessments 64
5.6.3 Laboratory Monitoring Algorithms 65
5.6.4 Defining Trigger Points for Preemptive Interventions 66
5.7 EBV VL Assessment for PTLD Diagnosis 66
5.8 EBV VL Assessments for Monitoring Response to PTLD Therapy and Predicting Relapse 67
5.9 EBV VL Assessments for Determining the Impact of New Immunosuppressive Regimens and Tailoring Individual Immunosuppression 69
5.10 Take Home Pearls 69
References 70
Chapter 6 76
Clinical Features and Diagnostic Evaluation of Posttransplant Lymphoproliferative Disorder 76
6.1 Introduction 76
6.1.1 Severe Infectious Mononucleosis, Clinical Categories, and Sites of PTLD 77
6.1.2 Clinicopathologic Correlates 80
6.1.3 Diagnostic Evaluation 81
6.1.3.1 Background Information on Patients 81
6.1.3.2 Initial Clinical Examination 82
6.1.3.3 Diagnostic and Screening Tests 83
General Tests and Non-EBV Specific Tests 84
EBV Specific Tests 87
Histopathology 89
6.1.4 Clinical Staging of PTLD 89
6.1.5 Differential Diagnoses 90
6.1.6 Ten Take Home Pearls 91
References 92
Chapter 7 96
Pathology 96
7.1 Introduction 97
7.1.1 General Pathologic Features and Classification 97
7.1.2 Differential Diagnosis 98
7.1.3 Multiparameter Approach to the Diagnosis of PTLD 98
7.2 Early Lesions 99
7.2.1 Plasmacytic Hyperplasia (PCH) 99
7.2.1.1 Histopathology 99
7.2.1.2 Ancillary Studies 99
7.2.2 Infectious Mononucleosis (IM)-Like PTLD 100
7.2.2.1 Histopathology 100
7.2.2.2 Ancillary Studies 100
7.2.3 Florid Follicular Hyperplasia 101
7.2.3.1 Histopathology 101
7.2.3.2 Ancillary Studies 101
7.3 Polymorphic PTLD 101
7.3.1 Histopathology 102
7.3.2 Ancillary Studies 102
7.4 Monomorphic PTLD 102
7.4.1 Monomorphic B-Cell PTLD 104
7.4.1.1 Histopathology 104
7.4.1.2 Ancillary Studies 104
7.4.2 Monomorphic T-Cell PTLD 106
7.4.2.1 Histopathology 106
7.4.2.2 Ancillary Studies 107
7.5 Classical Hodgkin Lymphoma Type PTLD 107
7.5.1 Histopathology 108
7.5.2 Ancillary Studies 108
7.6 Take Home Pearls 109
References 109
Chapter 8 112
Prognostic Factors for PTLD 112
8.1 Historical Background 113
8.2 Prognostic Factors for PTLD 114
8.3 Prognostic Indices 119
8.4 Take Home Pearls 122
References 122
Chapter 9 124
Treatment of PTLD 124
9.1 Introduction 124
9.2 Optimal Therapy for PTLD 125
9.3 Reduction of Immune Suppression 125
9.4 Surgery and Radiation Therapy 126
9.5 Antiviral Therapy 127
9.6 Interferon and Other Cytokines 127
9.7 Intravenous Immune Globulin 128
9.8 Anti-B Cell Antibodies 128
9.9 Chemotherapy 130
9.10 Cellular Immunotherapy 131
9.11 Role of Combination Therapies 132
9.12 Central Nervous System Disease 132
9.13 Monitoring Patients During Therapy 133
9.13.1 Conventional Monitoring of Graft and PTLD Status 133
9.13.2 EBV Viral Load Monitoring 134
9.13.3 Cellular Immune Responses 134
9.14 Conclusions 134
9.15 Take Home Pearls 135
References 135
Chapter 10 139
Prevention of Epstein–Barr Virus Infection and Posttransplant Lymphoproliferative Disease Following Transplantation 139
10.1 Introduction 139
10.2 Chemoprophylaxis Using Antiviral Therapy 140
10.2.1 Mechanisms of Action of Acyclovir and Ganciclovir 140
10.2.2 Animal Models of Chemoprophylaxis 141
10.2.3 Clinical Studies of Chemoprophylaxis 141
10.3 Immunoprophylaxis 142
10.3.1 Cellular Therapy 142
10.3.2 Passive Immunization 143
10.3.3 Active Immunization 145
10.4 Viral Load Monitoring and Preemptive Strategies of Prevention 145
10.5 Take Home Pearls 147
References 148
Chapter 11.a 151
Organ Specific Issues of PTLD – Kidney 151
11.a.1 Epidemiology 152
11.a.2 Clinical Presentation 152
11.a.3 Therapeutic Aspects 153
11.a.4 Outcome and Prognostic Factors 155
11.a.5 Take Home Pearls 155
References 156
Chapter 11.b 158
Posttransplantation Lymphoproliferative Disorder (PTLD) in Liver and Small Bowel Transplant Recipients 158
11.b.1 Introduction 159
11.b.2 PTLD Following Liver Transplantation 159
11.b.2.1 Incidence 159
11.b.2.2 Risk Factors 160
11.b.2.3 Presentation 161
11.b.2.4 Treatment 162
11b.2.4.1 Reduction or Discontinuation of Immunosuppression and Antiviral Therapies 162
11.b.2.4.2 Surgery and Radiotherapy 162
11.b.2.4.3 Monoclonal Antibodies 162
11.b.2.4.5 Conventional Chemotherapy 163
11.b.2.5 Prognosis 163
11.b.3 PTLD Following Small Bowel Transplantation 163
11.b.3.1 Incidence 164
11.b.3.2 Risk Factors 164
11.b.3.3 Presentation 164
11.b.3.4 Treatment 165
11.b.4 Take Home Pearls 165
References 166
Chapter 11.c 168
Heart and Lung Transplantation 168
11.c.1 Introduction 168
11.c.2 PTLD After Heart Transplantation 169
11.c.2.1 Epidemiology 169
11.c.2.2 Clinical Presentation 169
11.c.2.3 Treatment of PTLD 170
11.c.2.4 Outcomes 172
11.c.3 PTLD After Lung and Heart–Lung Transplantation 172
11.c.3.1 Epidemiology 172
11.c.3.2 Clinical Presentation 173
11.c.3.3 Treatment 173
11.c.3.4 Outcome 174
11.c.4 Take Home Pearls 174
References 175
Chapter 11.d 178
Posttransplant Lymphoproliferative Disease (PTLD) in Hematopoietic Stem Cell Transplantation (HSCT) 178
11.d.1 Introduction 178
11.d.2 Pathogenesis 179
11.d.3 Definitions and Diagnosis of EBV Related Disease Post-HSCT 179
11.d.4 Risk Factors 180
11.d.5 Prevention and Treatment 182
11.d.5.1 Prophylactic Therapy 182
11.d.5.2 Preemptive Therapy 183
11.d.6 Treatment of PTLD 184
11.d.7 Take Home Pearls 185
References 185
Chapter 12 188
Research Priorities and Future Directions 188
12.1 Introduction 188
12.2 Etiology/Pathogenesis of PTLD 188
12.3 Surveillance and Monitoring 189
12.4 Treatment of PTLD 189
Index 191