The competitive grant renewal proposes an integrated program of basic and clinical research to improve the short- and long-term efficacy of allogeneic hematopoietic stem cell transplantation (HSCT). Human candidate diseases for HSCT include patients with acquired (e.g aplastic anemia, autoimmune disease) and genetic (e.g. T-cell deficiency diseases, red blood cell disorders) non-malignant diseases, myelodysplastic syndromes (e.g. T-cell deficiency diseases, red blood cell disorders) non- malignant diseases, myelodysplastic syndromes (MDS), and myeloproliferative disorders. Efforts are focused firstly on the application of non-myeloablative HSCT regimens. The novel aspect of our approach of non-myeloablative HSCT is the use of optimized post-grafting immunosuppression not only to control graft-versus-host disease but also host-versus-graft reactions. This way, the need for toxic pre-transplant therapy has been largely eliminated. Initial emphasis is on HLA-matched related and unrelated transplants. A preclinical canine model focuses on the development of non-myeloablative HSCT strategies for less well matched recipients and on the us of targeted radiation therapy using monoclonal antibodies labeled with alpha-emitting radionuclides. Secondly, for patients with genetic diseases who do not have marrow donors, a project on gene therapy explores optimal gene transfer strategies in a preclinical canine model with ultimate application in human patients with Fanconi anemia. Another laboratory project is aimed at identifying critical cellular components needed to facilitate engraftment in the non-myeloablative setting, particularly when the underlying disease, e.g. MDS, or other conditions, e.g. ABO incompatibilities, pose unique obstacles to this form of therapy. The research studies are supported by five core units which provide sample acquisition and analysis, study design, data processing, statistical analyses, clinical support including that for multi-center studies, long- term follow-up, management of chronic graft-versus-host disease, and grant administration. The principles derived from the proposed studies will make it possible to provide more effective treatment to a greater number of patients.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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Henslee-Downey, Jean
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Fred Hutchinson Cancer Research Center
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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
Thakar, M S; Bonfim, C; Walters, M C et al. (2017) Dose-adapted post-transplant cyclophosphamide for HLA-haploidentical transplantation in Fanconi anemia. Bone Marrow Transplant 52:570-573
Burroughs, Lauri M; Shimamura, Akiko; Talano, Julie-An et al. (2017) Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders. Biol Blood Marrow Transplant 23:1669-1677
Vaughn, J E; Anwer, F; Deeg, H J (2016) Treatment of refractory ITP and Evans syndrome by haematopoietic cell transplantation: is it indicated, and for whom? Vox Sang 110:5-11
Aki, S Z; Inamoto, Y; Carpenter, P A et al. (2016) Confounding factors affecting the National Institutes of Health (NIH) chronic Graft-Versus-Host Disease Organ-Specific Score and global severity. Bone Marrow Transplant 51:1350-1353
Khera, Nandita; Gooley, Ted; Flowers, Mary E D et al. (2016) Association of Distance from Transplantation Center and Place of Residence on Outcomes after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 22:1319-1323
Karoopongse, Ekapun; Marcondes, A Mario; Yeung, Cecilia et al. (2016) Disruption of Iron Regulation after Radiation and Donor Cell Infusion. Biol Blood Marrow Transplant 22:1173-1181
Hoffmeister, P A; Storer, B E; Syrjala, K L et al. (2016) Physician-diagnosed depression and suicides in pediatric hematopoietic cell transplant survivors with up to 40 years of follow-up. Bone Marrow Transplant 51:153-6
Gallo, S; Woolfrey, A E; Burroughs, L M et al. (2016) Marrow grafts from HLA-identical siblings for severe aplastic anemia: does limiting the number of transplanted marrow cells reduce the risk of chronic GvHD? Bone Marrow Transplant 51:1573-1578
Festuccia, Moreno; Deeg, H Joachim; Gooley, Theodore A et al. (2016) Minimal Identifiable Disease and the Role of Conditioning Intensity in Hematopoietic Cell Transplantation for Myelodysplastic Syndrome and Acute Myelogenous Leukemia Evolving from Myelodysplastic Syndrome. Biol Blood Marrow Transplant 22:1227-1233

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