Extracorporeal Photopheresis (eBook)

Cellular Photoimmunotherapy

Hildegard T. Greinix, Robert Knobler (Herausgeber)

eBook Download: PDF

2012
227 Seiten
De Gruyter (Verlag)
978-3-11-027613-8 (ISBN)

Infos

Extracorporeal photopheresis (ECP) is the first FDA approved cellular photoimmunotherapy for cancer and has demonstrated efficacy in T-cell mediated disorders including prevention and treatment of acute and chronic graft-versus-host disease, organ transplant rejection, scleroderma, Crohn's disease and diabetes mellitus. Due to its exceptional safety profile ECP has gained wide international acceptance through the efforts of leading clinical investigators. Exciting preclinical data and clinical observations provide insight into the mechanisms of action of ECP and are the basis for further clinical investigations.

Univ. Prof. Dr. Hildegard T. Greinix, Prof. Dr. Robert Knobler, both Medical University of Vienna Departments of Internal Medicine I and Dermatology Vienna, Austria.

Autor

lt;!doctype html public "-//w3c//dtd html 4.0 transitional//en">

Univ. Prof. Dr. Hildegard T. Greinix, Prof. Dr. Robert Knobler, both Medical University of Vienna Departments of Internal Medicine I and Dermatology Vienna, Austria.

Inhalt

1 History of Extracorporeal Photopheresis 14
1.1 First Clinical Studies Using ECP 14
1.2 ECP for Treatment of CTCL and Other Diseases 15
1.3 Technical Developments in Use of ECP 15
1.4 Current Role of ECP 17
2 Technical Aspects 20
2.1 ECP in Children and Adolescents 20
2.1.1 Introduction 20
2.1.2 ECP Methodology and Instrumentation 21
2.1.3 Summary 32
2.2 ECP in Patients with Bleeding Risks 34
2.2.1 Anticoagulation with Heparin 34
2.2.2 Anticoagulation with Acid Citrate Dextrose 36
2.2.3 Anticoagulation during ECP in Patients with Bleeding Risks 37
2.2.4 Anticoagulation during ECP in Patients with Absolute Contraindications for Heparin Use 38
2.2.5 Vienna Experience on ECP with ACD-A 38
2.2.6 Recommendations and Conclusions 40
2.3 ECP with Central Venous Access 42
2.3.1 Arteriovenous Fistulas (AVFs) or Arteriovenous Grafts (AVGs) 42
2.3.2 Central Venous Catheters (CVCs) 43
2.3.3 Totally Implantable Central Venous Access Systems (Ports) 45
2.3.4 Summary/Conclusions 47
2.4 New Technical Developments 50
2.4.1 Extracorporeal Photopheresis Regulatory Recommendations 50
2.4.2 The Closed System’s New Technical Developments 51
2.4.3 Conclusions 57
3 Mechanisms of Action of ECP 60
3.1 Preclinical GVHD Model 60
3.1.1 Introduction 60
3.1.2 Results 60
3.1.3 Discussion 65
3.2 Preclinical Hypersensitivity Models 71
3.2.1 Introduction 71
3.2.2 The Experimental Model 71
3.2.3 Characterization of ECP/PUVA-Induced Treg 72
3.2.4 Interleukin-10 is a Crucial Mediator 72
3.2.5 Other Models and Data Indicating a Role of Treg in ECP 74
3.2.6 Conclusion 74
3.3 Mechanism of Action of ECP - Clinical Evidence 77
3.3.1 Introduction 77
3.3.2 Cellular Vaccination Hypothesis 77
3.3.3 Apoptosis of ECP-Treated Lymphocytes 78
3.3.4 Direct Effect of ECP on Effector Cells 79
3.3.5 ECP Modulation of Peripheral Blood Monocytes and Dendritic Cells 81
3.3.6 Distal Effects on Untreated Lymphocytes in GVHD 82
3.3.7 Emergence of Regulatory T cell Populations during ECP Treatment 84
3.3.8 Dysregulation of B Cell Homeostasis and Hallmarks of Improvement in ECP Treatment in GVHD 85
4 Extracorporeal Photopheresis in Acute Graft-versus-Host Disease 96
4.1 First-Line Therapy of Acute GVHD 96
4.1.1 When to Start First-Line Therapy 96
4.1.2 What First-Line Therapy to Use 96
4.1.3 Duration of First-Line Therapy and Response 97
4.1.4 Combination First-Line Therapy 97
4.2 Predicing GVHD Severity 98
4.3 Second-line Therapy of Corticosteroid-Refractory Acute GVHD 98
4.3.1 Defining Steroid-Refractory Acute GVHD 98
4.3.2 Second-Line Therapy with Immunosuppressive Agents 98
4.3.3 ECP in Corticosteroid-Refractory Acute GVHD 99
4.4 Conclusions on the Use of ECP in Acute GVHD 105
5 Extracorporeal Photopheresis in Chronic Graft-versus-Host Disease 110
5.1 Results of ECP in Cutaneous Manifestations of Chronic GVHD 110
5.1.1 Cutaneous Manifestations of Chronic GVHD 110
5.1.2 Results of Phase II Studies with Non-ECP Therapies for Cutaneous Chronic GVHD 111
5.1.3 Results of Phase II Studies with ECP Treatment for Cutaneous Chronic GVHD 111
5.1.4 Results of Two Phase II Randomized, Single-Blind, Multicenter Studies of ECP for Treatment of Cutaneous Chronic GVHD 112
5.1.5 Summary 116
5.2 Results of ECP in Extracutaneous Manifestations of Chronic GVHD 119
5.2.1 Introduction 119
5.2.2 Liver and Gastrointestinal (GI) GVHD 119
5.2.3 Ocular and Oral GVHD 123
5.2.4 Chronic GVHD of the Lungs 126
5.2.5 Summary 128
5.3 ECP in Chronic GVHD: Steroid-Sparing Effect 134
5.3.1 Introduction 134
5.3.2 Corticosteroids and Other Immunosuppressive Agents in Chronic GVHD 134
5.3.3 Overview of ECP in Chronic GVHD and its Steroid-Sparing Effect 136
5.3.4 Conclusions 137
5.4 Prediction of Response to ECP 140
5.4.1 Identification of Biomarkers in Chronic Graft-versus-Host Disease 140
5.4.2 Biomarkers for Prediction of Response to ECP 142
5.4.3 Conclusions 145
6 ECPforthe Prevention of Graft-versus-Host Disease 148
6.1 Introduction 148
6.2 Standard GVHD Prevention Strategies 148
6.2.1 Methotrexate 148
6.2.2 Cyclophosphamide 149
6.2.3 Calcineurin Inhibitors 149
6.2.4 Mycophenolate Mofetil 150
6.2.5 Sirolimus 150
6.3 GVHD Prevention with ECP: Potential Mechanism of Action 151
6.3.1 Targeting Dendritic Cells 151
6.3.2 Targeting Regulatory T Cell 153
6.3.3 Targeting Dendritic Cells and Regulatory T Cells 155
6.4 Extracorporeal Photopheresis during HCT Preparative Regimens 156
6.5 ECP for Prevention of Solid Organ Rejection 157
6.6 ECP for GVHD Prevention: Tolerogeneic DC and Treg Induction 158
6.7 Conclusions 159
7 ECP in Cutaneous T Cell Lymphoma 164
7.1 ECP for Treatment of CTCL 164
7.1.1 Treatment Schedule 166
7.1.2 Recommendations 167
7.2 Predictors of Response 170
7.3 Adjuvant Therapy 170
7.4 Monitoring during ECP Therapy 170
7.5 Conclusion 171
8 ECP in Scleroderma and Other Skin Diseases 176
8.1 Systemic Sclerosis 176
8.1.1 ECP in Systemic Sclerosis 176
8.2 ECP in Localized Scleroderma/Morphea 178
8.3 ECP in Autoimmune Bullous Diseases 179
8.4 Atopic Dermatitis 179
9 ECPinCrohn’s Disease 182
9.1 Results on ECP in Crohn’s Disease 182
9.2 Conclusions 183
10 Extracorporeal Photopheresis after Solid Organ/Tissue Transplantation 186
10.1 Prevention and Treatment of Solid Organ Transplant Rejection 186
10.1.1 Introduction 186
10.1.2 Immune Mechanisms of Acute and Chronic Allograft Rejection 187
10.1.3 Potential Mechanisms of Action of Photopheresis in the Treatment of Allograft Rejection 189
10.1.4 ECP in Lung Transplantation 191
10.1.5 ECP in Cardiac Transplantation 194
10.1.6 ECP in Renal Transplantation 197
10.2 ECP after Facial Transplantation 203
10.2.1 Introduction 203
10.2.2 Immunosuppression in Organ and Tissue Transplantation 203
10.2.3 Case Description 204
10.2.4 Conclusions 206
11 ECP in Diabetes Mellitus 212
11.1 Introduction 212
11.2 Prospective, Placebo-Controlled Clinical Study on Use of ECP 213
11.3 Results 214
11.3.1 Discussion of Study Results 214
11.4 Conclusions 217
12 Side Effects of Extracorporeal Photopheresis 220
12.1 Side Effects Concerning the Apheresis Procedure 220
12.2 Side Effects Concerning 8-Methoxypsoralen 221
12.3 Miscellaneous 222
13 Summary 226

Produkt-Details

• Erscheint lt. Verlag: 1.10.2012
• Zusatzinfo: 50 col. ill., 16 b/w tbl.
• Verlagsort: Berlin/Boston
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie
• ISBN-10: 3-11-027613-5 / 3110276135
• ISBN-13: 978-3-11-027613-8 / 9783110276138