
Bone Marrow Transplantation Across Major Genetic Barriers.
Title:
Bone Marrow Transplantation Across Major Genetic Barriers.
Author:
Reisner, Yair.
ISBN:
9789814271271
Personal Author:
Physical Description:
1 online resource (250 pages)
Contents:
Contents -- Preface -- Crossing HLA Barriers by "Megadose" Stem Cell Transplants -- Introduction -- Crossing the HLA Barrier in SCID Patients -- The Experimental Basis for "Megadose" Transplants in Leukemia Patients -- How "Megadose"Transplants Overcome the Immune Barrier Initial Evidence for Tolerance Induction by Human CD34+ Hematopoietic Progenitor Cells -- A Major Remaining Challenge: Enhancing Immune Reconstitution -- References -- The Haploidentical Option for High-Risk Hematological Malignancies -- Introduction -- Overcoming HLA-Histocompatibility Barriers -- Clinical Outcomes -- a) Engraftment and GvHD -- b) Leukemia Relapse -- c) Non-Leukemic Mortality -- d) Event-Free Survival -- Haploidentical SCT Based on Feto-Maternal Microchimaerism -- Conclusions -- References -- Haploidentical Allogeneic Hematopoietic Cell Transplantation in Adults Using CD3/CD19 Depletion and Reduced Intensity Conditioning -- Introduction -- Haplo RIC Using CD3/CD19-depleted Grafts -- Literature -- Unmanipulated HLA-Mismatched/Haploidentical Blood and Marrow Hematopoietic Stem Cell Transplantation -- Introduction -- Clinical Results of HLA-Mismatched/Haploidentical HSCT -- Establishment of the GIAC Protocol -- Clinical Results -- Engraftment -- Graft-vs-host disease -- Relapse and management -- Transplant-related mortality and survival -- Posttransplant immune reconstitution -- Immune Tolerance Basis for Unmanipulated HLA-Mismatched Blood and Marrow HSCT -- Simultaneous Induction of T Cell Tolerance in Bone Marrow and Peripheral Blood Grafts by Treating Healthy Donors with G-CSF -- Maintaining the Hyporesponsiveness of T Cells After in vitro Mixture of G-PB and G-BM in Different Proportions -- Combination of Immunologic Suppressive Agents -- Conclusions -- References -- Alloanergization in Haploidentical Hematopoietic Stem Cell Transplantation -- Introduction.
The Immunological Basis of Alloanergization -- Previous Clinical Studies -- Patients, Donors and Preparative Regimen -- Ex Vivo Alloanergization of Bone Marrow -- Pharmacological GvHD Prophylaxis and Supportive Care -- Engraftment and TRM -- GvHD -- Viral Reactivation and Infection -- Immune Reconstitution -- Outcome -- Summary -- In Vitro Studies of Efficacy and Specificity of Alloanergization of Human Peripheral Blood Mononuclear Cells -- Alloanergization Reduced Alloproliferative Responses in both CD4+ and CD8+ Donor T Cells -- Functional CD4+ and CD8+ T Cell Responses to Human Herpes Viruses Were Retained after Alloanergization -- Tumor-associated Antigen-specific CD8+ and CD4+ T Cell Responses Were Also Retained after Alloanergization -- Summary -- New Clinical Study -- Stem Cell Source and Conditioning Regimen -- Donor T Cell and Allostimulator Sources -- Timing of Infusion of Alloanergized Donor T Cells -- Dose Escalation of Alloanergized Donor T Cell Infusion -- Measurement of Functional Antigen-specific Immune Reconstitution -- Final Summary -- References -- Hematopoietic Stem Cell Transplantation Across Genetic Barriers Using a Nonmyeloablative Conditioning Regimen -- Introduction -- Evolving Strategies to Overcome HLA Barriers -- Effective T Cell Depletion: A Pivotal Platform in the Development of Haploidentical/Mismatched Transplantation -- Early Development in T Cell Depletion -- Recent Advances in T Cell Depletion -- Positive CD34 Selection -- CD3+/CD19+ Depletion -- In vivo T cell Depletion Using Alemtuzumab or ATG -- The Rationale of Haploidentical/Mismatched Transplantation Using Nonmyeloablative Conditioning -- Recent Studies Using T Cell-depleted Hematopoietic Cell Grafts Involving Nonmyeloablative Conditioning (Table 2) -- Results from Tuebingen/Dresden -- Results from Massachusetts General Hospital.
Results from Johns Hopkins University/Fred Hutchinson Cancer Research Center -- Results from Osaka University -- Results from Tokyo University -- Results from Duke University -- Strategies to Improve the Outcome of Patients with Haploidentical Transplantation Using TCD Allografts -- Harnessing the Beneficial Effects of the Natural Killer Cell /KIR Ligand -- Harnessing the Beneficial Effects of the Nonfetal Maternal Antigen -- Selective T Cell Depletion of Allografts -- Cotransplantation of Mesenchymal Stem Cells -- Prophylatic/Pre-emptive Donor Lymphocyte Infusion -- Adoptive Immunotherapy and Vaccination -- Conclusions -- References -- Deploying Natural Killer Cell Allotherapy in the Setting of HLA-Haplotype-Mismatched Hematopoietic Stem Cell Transplantation -- Introduction -- NK Cell Alloreactivity in Allogeneic Hematopoietic Transplantation: Preclinical Data -- Donor-Versus-Recipient NK Cell Alloreactivity in Allogeneic Hematopoietic Transplantation -- Guidelines for NK-Alloreactive Donor Selection -- References -- Adoptive Immunotherapy for Prophylaxis and Therapy of Infectious Complications After Allogeneic Hematopoietic Stem Cell Transplantation -- Introduction -- Infections After Allogeneic-HSCT -- Cytomegalovirus -- Epstein-Barr Virus -- Adenovirus -- Fungal Infections -- Adoptive T Cell Therapy -- Donor Lymphocyte Infusions -- Depletion of Alloreactive T Cells -- Enrichment of Antigen-specific T Cells -- Clinical Trials -- Cytomegalovirus -- Epstein-Barr Virus -- Adenovirus -- Fungus-specific T Lymphocytes -- Conclusions -- References -- The Challenge in Hematopoietic Stem Cell Transplantation: Shortening the Immunodeficiency Period -- Introduction -- Depletion of Alloreactive T Cells -- Antivirus-Specific Immunotherapy -- Ex Vivo Expansion of a Human Progenitor Committed to the T Cell Lineage and Able to Seed the Thymus -- References.
Treatment of Adenovirus Infection After Haploidentical Stem Cell Transplantation in Children -- Introduction -- Structure of Adenovirus -- The Role of T Cells in Adenovirus-Specific Immunity -- Incidence and Risk Factors of Adenovirus Infection Post-HSCT -- Diagnosis and Surveillance of Adenovirus Infection After Haploidentical Transplantation -- Clinical Symptoms of Adenovirus Infection Posttransplant -- Pharmacologic Treatment of Adenovirus Infections Post-HSCT -- Adoptive T Cell Transfer in Adenovirus Infections Post-HSCT -- Conclusion -- Acknowledgments -- References -- Regulatory T Cell Therapy for Immunomodulation After Allogeneic Hematopoietic Cell Transplantation -- Introduction -- Evidence for Immunomodulation by Endogenous Regulatory T Cells in the Murine BMT Models -- Possible Mechanisms of Regulatory T Cell Control of GvHD -- Impact of Regulatory T Cells on Antitumor Immunity -- Differential Susceptibility of Regulatory T Cells to Immunosuppressive Agents -- Calcineurin Inhibitors: Cyclosporine A and Tacrolimus (FK506) -- Impact of Rapamycin on Treg and Effector T Cells -- Mycophenolate Mofetil -- Impact of Glucocorticosteroids on Treg -- Anti-IL-2 Receptor Antibodies -- FTY720 -- The Role of Regulatory T Cells in Clinical Allogeneic Hematopoietic Cell Transplantation -- Isolation and Expansion Strategies for Human Regulatory T Cells -- Isolation and Expansion -- Clinical Trials -- Summary and Conclusions -- References -- Pathogen-induced Immune Regulation in Transplantation -- Introduction -- Fungi and Immunity: An Intriguing Relationship -- Dendritic Cells in Hematopoietic Transplantation -- Dendritic Cells Provide Antifungal Immune Resistance -- Dendritic Cells Induce Protective Tolerance -- Antifungal Treg Concomitantly Suppress Inflammation and Alloreactivity -- IDO Contributes to Protective Tolerance.
Exploiting TLR for Transplantation Tolerance: The Lesson from Thymosin α1 -- Immunotherapeutic Perspectives -- Acknowledgements -- References -- Immune Reconstitution After Haploidentical Hematopoietic Stem Cell Transplantation -- Introduction -- Factors in the Development of Immune Competence -- Conditioning Regimen -- T Cell Depletion -- HSC Source -- Recipient Age -- GvHD -- Immune Reconstitution -- Immunophenotypic Analysis of T Lymphocytes -- Immunophenotypic Analysis of B Lymphocytes -- Antigen-Specific Immunity Following HSCT -- Antigen-Specific T Lymphocyte Function -- Antigen-Specific B Lymphocyte Function -- Attempts to Improve Post-HSCT Immune Reconstitution -- Cytokine Therapy -- Keratinocyte Growth Factor -- Androgen Receptor Antagonists -- Adoptive Cellular Therapy -- Delayed Lymphocyte Infusions -- Antigen-Specific Donor Lymphocyte Infusions -- Alloreactive-Depleted Donor Lymphocyte Infusions -- Anergization -- Haploidentical HSCT -- Acknowledgment -- References -- The Role of the Thymus in Hematopoietic Stem Cell Transplantation -- Introduction -- Normal Postnatal Thymic T Cell Maturationand Export -- The Thymic Lymphoid Compartment -- The Thymic Stromal Compartment -- Pathways of Posttransplant T Cell Regeneration -- Thymic-Independent T Cell Regeneration -- Thymic-dependent T Cell Regeneration:The Phenotype… -- …and the Quality -- Limitations on Thymus-dependent T Cell Regeneration -- Human Thymic Function in the Context of Acute GvHD -- Pathomechanisms of Thymic Insufficiency:Insights from Preclinical GvHD Models -- Thymic Dysfunction as a Link to Autoimmunity/Chronic GvHD? -- Interventions to Improve Immune Regeneration via Protection of Thymic Epithelium by Fibroblast Growth Factor 7 -- Conclusion -- References -- Human T Cell Differentiation: New Techniques, Old Challenges -- Introduction.
The Multipotent Hematopoietic Stem Cell and T Cell Potency.
Abstract:
The importance of bone marrow transplantation for patients who do not have a matched sibling donor cannot be overestimated. This subject has always been in the public domain, accentuated by dramatic appeals, from time to time, to search for matched volunteer donors in the public at large. Unfortunately, the availability of such donors is limited, due to the remarkable genetic diversity of humans. Thus, although registries of such volunteers now include more than seven million individuals, we still face the problem of finding a matched donor for about 30 per cent of patients in need. To address this burning issue, extensive clinical and basic research is performed in leading institutes around the world. This book presents updated accounts of the different aspects of this research. The scope of the book is very wide, including strategies to overcome graft vs. host (GVH) disease and graft rejection, cell therapy to prevent leukemia relapse, and a range of modalities to improve immune reconstitution after transplantation. In addition, new approaches to induce immune tolerance towards organ transplants by means of hematopoietic stem cell transplantation is extensively reviewed.
Local Note:
Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2017. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.
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