The overall goal of this program project is to improve allogeneic hematopoietic cell transplantation (HCT) as treatment for hematological malignancies. Specifically we proposed laboratory and clinical studies to broaden the availability of transplantation, to decrease the incidence and severity of graft-versus-host disease, and to reduce the incidence of malignant disease recurrence post transplant. Four individual projects are proposed: 1. Immunogenetics of Graft-versus-host Disease. 2. Nonmyeloablative Hematopoietic Cell Allotransplants. 3. Specific Adoptive Immunotherapy of Myeloid Malignancy. 4. Targeting T Cell Reactivity for Leukemia Eradication. In addition, core support is requested in biostatistics, molecular diagnostics, cell processing, long-term follow-up, and administration. Our ability to successfully carry out the proposed work is greatly benefited by: (1) the existence of a large group of investigators all focused on the general topic of HCT;(2) strong preclinical research programs at our Center in support of this topic;and, (3) treatment of >500 transplant patients at our Center each year
The Program Project has direct relevance to the >27,000 patients who undergo allogeneic HCT for treatment of hematopoietic malignancies each year. The work proposed promises to increase the availability of transplantation and to make it safer and more effective. Lessons learned from our planned studies will apply to issues of transplant tolerance, the molecular basis of malignant disease progression, and especially the immunotherapy of cancer.
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