The long-range goal of this study is to develop the capability of providing allogeneic marrow transplantation to patients who lack an HLA genotypically identical sibling donor. Both """"""""partially matched"""""""" related and phenotypically matched unrelated individuals will be considered as alternative donors and the feasibility and efficacy of transplantation in this setting will be evaluated. Although successful HLA incompatible transplants have been performed, it is not clear whether disparity for any given HLA antigen will cause a significant allograft reaction. For this reason, we will continue to analyze the role of HLA in marrow transplantation and will attempt to define the minimal degree of HLA class I and class II compatibility required to reduce the incidence of graft rejection and graft-versus-host disease (GVHD). Further elucidation of the most relevant genetic factors will be especially important in helping to establish practical matching criteria for selecting volunteer unrelated marrow donors. Pilot clinical trials will be undertaken to determine whether additional immunosuppressive therapy, including total lymphoid irradiation (TLI) and monoclonal antibodies, can reduce the risk of rejection. This objective must be successfully addressed before T cell depletion of donor marrow can be safely used for the prevention of GVHD in mismatched transplants. The laboratory components of this project will address three transplanted-related questions. First, we will study T cell reactivity immediately following transplantation by cloning and limiting dilution methods to determine whether variants of conventionally-defined HLA alleles or undetected HLA determinants can induce specific T cell reactivity. Second, we will determine the frequency of recombination within the HLA-D region, and study whether such recombination in putative identical siblings might increase the risk of GVHD. Third, we will study the suppressor T cells that regulate autoreactive and non- HLA-reactive effector cells, and the role that these suppressors play in preventing anti-host responses and induction of tolerance in HLA identical transplants.

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National Cancer Institute (NCI)
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McCune, Jeannine S; Storer, Barry; Thomas, Sushma et al. (2018) Inosine Monophosphate Dehydrogenase Pharmacogenetics in Hematopoietic Cell Transplantation Patients. Biol Blood Marrow Transplant 24:1802-1807
Deegan, Anthony J; Talebi-Liasi, Faezeh; Song, Shaozhen et al. (2018) Optical coherence tomography angiography of normal skin and inflammatory dermatologic conditions. Lasers Surg Med 50:183-193
Leger, Kasey J; Baker, K Scott; Cushing-Haugen, Kara L et al. (2018) Lifestyle factors and subsequent ischemic heart disease risk after hematopoietic cell transplantation. Cancer 124:1507-1515
Schmitt, Michael W; Pritchard, Justin R; Leighow, Scott M et al. (2018) Single-Molecule Sequencing Reveals Patterns of Preexisting Drug Resistance That Suggest Treatment Strategies in Philadelphia-Positive Leukemias. Clin Cancer Res 24:5321-5334
Shaw, Bronwen E; Syrjala, Karen L; Onstad, Lynn E et al. (2018) PROMIS measures can be used to assess symptoms and function in long-term hematopoietic cell transplantation survivors. Cancer 124:841-849
Jamani, Kareem; Onstad, Lynn E; Bar, Merav et al. (2018) Quality of Life of Caregivers of Hematopoietic Cell Transplant Recipients. Biol Blood Marrow Transplant 24:2271-2276
Ogimi, Chikara; Xie, Hu; Leisenring, Wendy M et al. (2018) Initial High Viral Load Is Associated with Prolonged Shedding of Human Rhinovirus in Allogeneic Hematopoietic Cell Transplant Recipients. Biol Blood Marrow Transplant 24:2160-2163
Salter, Alexander I; Pont, Margot J; Riddell, Stanley R (2018) Chimeric antigen receptor-modified T cells: CD19 and the road beyond. Blood 131:2621-2629
Lee, Stephanie J; Nguyen, Tam D; Onstad, Lynn et al. (2018) Success of Immunosuppressive Treatments in Patients with Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant 24:555-562
Bar, Merav; Flowers, Mary E D; Storer, Barry E et al. (2018) Reversal of Low Donor Chimerism after Hematopoietic Cell Transplantation Using Pentostatin and Donor Lymphocyte Infusion: A Prospective Phase II Multicenter Trial. Biol Blood Marrow Transplant 24:308-313

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