Bone Marrow Transplantation—Past, Present and Future

Thomas, E. Donnall

doi:10.1111/j.1365-3083.1994.tb03383.x

Cited by 32 publications

(18 citation statements)

References 35 publications

(14 reference statements)

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“…The Seattle team lead by Dr. E. Donnell Thomas performed the first HLA matched sibling donor transplant for a patient with advanced leukemia [54]. A detailed history of these milestone events has been summarized by Dr. Good in his 1970 Lasker award lecture [55] and by Dr. Thomas in his Nobel award lecture given in December of 1990 [56]. Additional early reports confirmed the feasibility and extended the application of HLA-matched sibling transplants for treatment of immune deficiency diseases [57][58][59], aplastic anemia [60] and hematological malignancies [61].…”

Section: Genetic Matching and The Modern Era Of Hsctmentioning

confidence: 99%

Genetics of allogeneic hematopoietic cell transplantation. Role of HLA matching, functional variation in immune response genes

et al. 2007

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Successful outcome following hematopoietic stem cell transplantation (HSCT) is ultimately determined by the ability to achieve sustained engraftment and immune reconstitution, control of graft-versus-host disease (GVHD), and in patients with hematological malignancy the complete eradication of abnormal or malignant cells. GVHD, which can be a serious and fatal complication, is an immune reaction that is initiated by donor T cells in response to recipient alloantigens. Genetic variation in both patient and donor can significantly affect transplant outcome by causing disparity for transplant antigens, and by altering the function of immune response genes that control cellular activation and inflammation. Genetic variation can modulate the intensity of the alloimmune response, the risk of transplant-related organ toxicity and mortality, and may also affect the development of tolerance and the reconstitution of the immune system following HSCT.

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Section: Genetic Matching and The Modern Era Of Hsctmentioning

confidence: 99%

Genetics of allogeneic hematopoietic cell transplantation. Role of HLA matching, functional variation in immune response genes

et al. 2007

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“…Successful engraftment was achieved only by selecting a twin donor or a sibling donor identical for human leukocyte antigens (HLAs) (1). Subsequent studies of partially HLAmatched related donors revealed that the degree of HLA incompatibility correlated with the incidence of graft failure and graft versus host disease (GVHD) (2,3).…”

Section: Overviewmentioning

confidence: 99%

Marrow Transplantation From Unrelated Volunteer Donors

et al. 1995

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Marrow transplants from human leukocyte antigen (HLA)-compatible unrelated volunteer donors have become feasible for more than 30% of patients without a family match and have allowed long-term, disease-free survival in 15-65% of patients with a variety of hematological disorders. However, unrelated donor transplants have a higher incidence of graft failure and graft versus host disease (GVHD) than do HLA-matched sibling transplants. This increase may be due to disparities between donor and recipient for undetected HLA determinants or for non-HLA histocompatibility genes. Because of the large number of HLA loci and their high degree of polymorphism, fully compatible donors will not be found for most patients. Fortunately, a limited degree of HLA mismatch does not necessarily impair long-term survival in patients with hematologic malignancy. Current studies are defining the risk associated with mismatching for each histocompatibility locus and are developing methods for marrow transplantation that can decrease morbidity and improve survival despite genetic disparity between donor and recipient. Annu. Rev. Med. 1995.46:169-179. Downloaded from www.annualreviews.org Access provided by University of California -San Francisco UCSF on 02/04/15. For personal use only.Quick links to online content Further ANNUAL REVIEWS

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“…The canine allogeneic HCT model has a remarkable track record of translating therapies into clinical protocols for human HCT (15), and we propose to use the canine model of mixed hematopoietic chimerism as a platform to develop a miHA vaccine (16). Stable mixed hematopoietic chimerism is achieved following 200 centigray (cGy) total body irradiation (TBI), MHC-identical marrow infusion, and a short course of post-grafting immunosuppression (16).…”

Section: Introductionmentioning

confidence: 99%

Development of a Minor Histocompatibility Antigen Vaccine Regimen in the Canine Model of Hematopoietic Cell Transplantation

et al. 2015

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Background Minor histocompatibility (miHA) antigen vaccines have the potential to augment graft-versus-tumor effects without graft-versus-host disease (GVHD). We used mixed hematopoietic chimerism in the canine model of MHC-matched allogeneic hematopoietic cell transplantation (HCT) as a platform to develop a miHA vaccination regimen. Methods We engineered DNA plasmids and replication-deficient human adenovirus type 5 (rAd5) constructs encoding large sections of canine SMCY and the entire canine SRY gene. Results Priming with rAd5 constructs and boosting with ex vivo plasmid-transfected dendritic cells and cutaneous delivery of plasmids with a particle-mediated epidermal delivery device (PMED) in two female dogs induced antigen-specific T cell responses. Similar responses were observed following a prime-boost vaccine regimen in three female HCT donors. Subsequent donor lymphocyte infusion resulted in a significant change of chimerism in 1 of 3 male recipients without any signs of GVHD. The change in chimerism in the recipient occurred in association with the development of CD4+ and CD8+ T cell responses to the same peptide pools detected in the donor. Conclusions These studies describe the first in vivo response to miHA vaccination in a large, outbred animal model without using recipient cells to sensitize the donor. This model provides a platform for ongoing experiments designed to define optimal miHA targets, and develop protocols to directly vaccinate the recipient.

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Bone Marrow Transplantation—Past, Present and Future

Cited by 32 publications

References 35 publications

Genetics of allogeneic hematopoietic cell transplantation. Role of HLA matching, functional variation in immune response genes

Genetics of allogeneic hematopoietic cell transplantation. Role of HLA matching, functional variation in immune response genes

Marrow Transplantation From Unrelated Volunteer Donors

Development of a Minor Histocompatibility Antigen Vaccine Regimen in the Canine Model of Hematopoietic Cell Transplantation

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