Chronic Graft Versus Host Disease: Interdisciplinary Management

Half-title......Page 3
Title......Page 5
Copyright......Page 6
Contents
......Page 7
Contributors
......Page 11
Preface
......Page 15
Part I: General Principles......Page 17
The Beginning of HSCT......Page 19
Political Effects of Chronic GVHD in the Late Seventies......Page 20
References......Page 22
Donor Tcell Activation......Page 24
Cytokine Secretion by Donor T Cells......Page 26
Cellular Effectors......Page 27
Tolllike Receptors and Innate Immunity......Page 28
References......Page 29
Factors that Affect the Pathophysiology of cGVHD......Page 33
Thymic Regulation......Page 34
Role of Pathogens in Development of cGVHD......Page 35
Tregs in cGVHD......Page 36
Biomarkers in cGVHD......Page 37
Impact of Immune Reconstitution on the Development of cGVHD......Page 38
How cGVHD may be Classified by Pathophysiology in the Future......Page 39
References......Page 40
Introduction......Page 47
CD4 Cells Interacting with Recipient B Cells That Express Allogeneic MHCII Is Crucial......Page 48
Does the P→F1 SLE-CGVHD Model Reflect Clinical cGVHD......Page 49
Induction Phase......Page 50
Why cGVHD in the B10.D2 (or B6.C)→BALBc Model......Page 51
Is CGVHD an Autoimmune Disease......Page 53
References......Page 56
1980–1990......Page 62
1990–2000......Page 64
Peripheral Blood versus Bone Marrow Grafts......Page 65
HLA-Mismatched Transplants......Page 67
Future Challenges......Page 68
References......Page 69
Practical Approaches in the Clinical Assessment of cGVHD......Page 72
Skin and Dermal Appendages......Page 77
Mouth......Page 80
Other Clinical Monitoring......Page 82
What to Photograph......Page 83
References......Page 84
Established Risk Factors......Page 86
Peripheral Blood Stem Cell Transplwantation......Page 87
Limited and Extensive......Page 88
Testing Johns Hopkins II Predictive Model in Other Data Sets
......Page 89
Expression of OX40 (CD134)......Page 90
Predictive Factors in Children with Chronic GVHD......Page 91
References......Page 92
Serum and Cellular Cytokine Production and the Th1/Th2 Paradigm in GVHD......Page 95
Immunological and Molecular Characterization of T Cells......Page 96
New Approaches and Concepts......Page 97
References......Page 98
Part II: Clinical Management......Page 101
Historical Perspective of cGVHD Classification and Prognostic Factors......Page 103
NIH Consensus Criteria for Grading and Staging of GVHD
......Page 105
Skin......Page 107
Guidelines for Global Scoring of cGVHD
......Page 108
Histopathological Aspects of cGVHD......Page 109
Overview of Histologic Studies......Page 110
Skin......Page 112
Liver......Page 113
Reporting Results of Biopsies......Page 114
Retrospective Validation of NIH Staging and Grading......Page 115
References......Page 116
Immunosuppression Mediated by Corticosteroids......Page 117
Metabolism......Page 119
Introduction......Page 120
Mechanism of Action......Page 121
Distribution......Page 122
Drug Interactions......Page 123
Drug Interactions......Page 124
Pharmacology......Page 125
Therapeutic Drug Monitoring......Page 126
Thalidomide......Page 127
Pharmacology......Page 128
Distribution......Page 129
References......Page 130
T-cell Depletion Ex Vivo......Page 133
Prophylaxis with Combined Immunosuppression......Page 134
Regulatory T Cells......Page 136
References......Page 137
Indications for Systemic Treatment of Chronic GVHD......Page 140
Initial Treatment......Page 141
Role of Other Agents for Initial Treatment of Chronic GVHD......Page 143
Potential Effects of Immunosuppressive Treatment on Risk of Recurrent Malignancy......Page 144
Prevention of Infection during Treatment of Chronic GVHD [3, 4, 28]......Page 145
Outcomes after Initial Treatment of Chronic GVHD......Page 146
References......Page 148
Introduction......Page 150
Sirolimus......Page 151
Extracorporeal Photoimmunotherapy......Page 152
Thalidomide......Page 153
Mycophenolate mofetil......Page 155
Topical Phototherapy......Page 156
Other Agents with Possible Activity......Page 157
References......Page 158
14 Evaluating Therapeutic Response in Chronic Graft versus Host Disease......Page 162
Considerations in Selecting Indicators for Measuring Response......Page 163
Definitions of Properties That Apply to Measurement Scales......Page 164
Limitations of Historical Approaches Used to Measure Response in Chronic GVHD......Page 165
NIH Consensus Criteria for Evaluating Response in Chronic GVHD......Page 167
Future Directions with the NIH Response Criteria......Page 170
References......Page 171
15 General Principles of Ancillary and Supportive Care......Page 173
References
......Page 181
Part III: Organ Site or System-Specific Manifestations......Page 183
Presentation......Page 185
Diagnosis......Page 187
Treatment......Page 191
Phototherapy......Page 192
Extracorporeal Photopheresis......Page 193
Future......Page 194
References......Page 195
Oral Mucosal cGVHD......Page 198
Salivary Gland cGVHD......Page 199
Diagnosis......Page 203
Significance for Prognosis and Clinical Course......Page 204
Management......Page 205
Management of Oral Mucosal cGVHD......Page 206
Management of Salivary Gland cGVHD......Page 207
References......Page 210
Clinical Manifestations......Page 215
Pathophysiology......Page 218
Management......Page 219
Future Direction......Page 220
References......Page 221
Incidence......Page 223
Clinical Grading System......Page 224
Symptoms and Signs......Page 225
Histology......Page 226
Treatment and Response......Page 227
References......Page 230
Significance for prognosis......Page 232
Prevention......Page 234
Incidence......Page 235
Diagnosis......Page 237
Significance for Prognosis......Page 238
Gallbladder and Biliary Problems......Page 240
Site-Specific Therapy......Page 241
References......Page 242
Clinical Assessment......Page 245
Chest Imaging......Page 246
Therapy and Outcome......Page 247
Risk Factors and Epidemiology......Page 249
Therapy and Outcome......Page 250
References......Page 251
Thrombocytopenia in Chronic GVHD......Page 254
Red Blood Cell Abnormalities in Chronic GVHD......Page 256
References......Page 257
Peripheral Nervous System Manifestations of cGVHD......Page 259
Polymyositis......Page 260
Posttransplant Peripheral Neuropathy......Page 261
Central Nervous System cGVHD A Real Entity......Page 262
cGVHD and CNS Demyelinative Disease......Page 263
cGVHD and Immune-Mediated Encephalitis......Page 265
References......Page 266
Scope of Chapter......Page 268
Frequently Identified Musculoskeletal Problems......Page 269
Fasciitis......Page 270
Clinical Manifestations of Osteoporosis......Page 271
Management of Glucocorticoid-Induced Osteoporosis......Page 272
GVHD-Related Neurological Abnormalities......Page 273
Contractures......Page 274
Fatigue......Page 275
Edema......Page 276
Myasthenia Gravis......Page 278
Conclusion/Summary......Page 279
References......Page 282
Syndromic Approach to the Patient with cGVHD......Page 284
General Approach to the Patient with cGVHD and Fever of Acute Onset......Page 285
Respiratory Infections in cGVHD......Page 286
Laboratory Tests Bronchoalveolar Lavage Blood and Urine......Page 287
Bacterial Pneumonia......Page 288
Respiratory Viruses......Page 289
Fungal Disease......Page 290
Skin and Soft Tissue Infections......Page 292
Central Nervous System Infections in cGVHD......Page 293
Intravenous Immunoglobulin......Page 294
Prophylactic Antibiotics......Page 295
Antifungal Prophylaxis......Page 296
CMV Prophylaxis......Page 297
Infections Related to Specific Immunosuppressive Treatments......Page 298
References......Page 299
Treatment......Page 305
Treatment......Page 307
Definition and Incidence......Page 308
Definition and Incidence......Page 309
Hyperlipidemia......Page 310
Abnormal Thyroid Fuction......Page 311
Case 2......Page 312
Case 3......Page 313
References......Page 314
Case Vignette 1......Page 318
Clinical Course......Page 319
Future Directions......Page 320
Clinical Course......Page 321
Incidence......Page 322
Presentation......Page 323
Future......Page 324
Clinical Course......Page 325
Clinical Course......Page 326
References......Page 327
Activity Limitations and Work Change......Page 330
Helplessness......Page 331
Concentration......Page 332
Agitation......Page 333
Sexuality......Page 334
Cognitive Development......Page 335
Treatment Options in Response to Needs......Page 338
References......Page 339
ocular effects......Page 342
Chronic Obstructive Lung Disease......Page 343
Secondary Malignancies......Page 344
Solid Tumors......Page 345
Skin and Mucosal Carcinoma and cGVHD......Page 346
Key Points......Page 347
References......Page 348
Defining HRQOL......Page 351
Distinguishing HRQOL from Symptoms and Functional Status......Page 352
Considerations in Selecting a Measure of HRQOL, Symptoms or Functional Status in cGVHD......Page 353
Impact of cGVHD on HRQOL, Symptoms and Functional status......Page 357
Minimally Important Clinical Difference......Page 359
References......Page 360
Part IV: Special Considerations in Chronic GVHD......Page 365
General Considerations......Page 367
Management and Evaluation of Chronic GVHD......Page 368
Case-Report Forms......Page 369
Selection of Endpoints......Page 370
Supporting Information from Physician and Patient Participants......Page 371
Prevention Trials......Page 372
Studies Intended for Regulatory Review......Page 373
References......Page 374
Impact of Stem-Cell Source on cGVHD: Bone Marrow versus Peripheral Blood Stem Cells......Page 376
Chronic GVHD after ReducedIntensity Conditioning Regimens and Donor Leukocyte Infusions......Page 378
Chronic GVHD after Umbilical Cord Blood Transplantation......Page 380
References......Page 382
Incidence of cGVHD in Pediatrics......Page 385
Peripheral Blood Stem Cells......Page 386
Umbilical Cord Blood......Page 387
Pathobiology......Page 388
Musculoskeletal......Page 389
Mouth......Page 390
Respiratory Tract......Page 391
Immune System......Page 392
Pentostatin......Page 393
Hydroxychloroquine......Page 394
Toxicity and Late Effects......Page 395
References......Page 396
Interdisciplinary Practice - Defining Features and Determinants of Success......Page 402
Element 1 Composition Coordination and Leadership of the Interdisciplinary cGVHD Team......Page 403
Disease Management Model......Page 404
Element 3 Communication and Collaboration......Page 405
Element 4 Access to the Full Range of Disciplines and Therapies......Page 406
Element 6 Involvement of Patient and Family......Page 407
Element 7 Coordination and Continuity of Care Between Specialty Center and Community......Page 408
Conclusions and Directions for Future Research......Page 409
References......Page 410
35 Patient Advocacy, Education and Psychosocial Support......Page 412
The Impact of cGVHD......Page 413
Patient and Research Advocacy......Page 414
Education......Page 415
Peer Support......Page 418
Public Policy......Page 419
References......Page 420
36 Future Directions......Page 422
Index
......Page 425