Post-Transplant Lymphoproliferative Disorders

von: Vikas R. Dharnidharka, Michael Green, Steven A. Webber

Springer-Verlag, 2010

ISBN: 9783642016530 , 190 Seiten

Format: PDF, OL

Kopierschutz: Wasserzeichen

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Post-Transplant Lymphoproliferative Disorders


 

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