Two overall objectives will be pursued in our continued efforts to treat patients with otherwise fatal nonmalignant hematologic diseases by allogeneic hematopoietic cell transplantation. One is to reduce regimen-related toxicities and transplant-related complications, including graft rejection and graft-vs-host disease. The other is to broaden the choice of hematopoietic cell donors beyond HLA-matched relatives and unrelated volunteers by including grafts of unrelated cord blood and HLA-haploidentical marrow cells. Nonmalignant disorders include three distinct disease entities, aplastic anemia. Fanconi anemia, and inherited diseases of the hematopoietic and immune systems. In order to assure accrual of patients with these relatively infrequent diseases to the proposed protocols, we have taken two steps. The first has been to include other academic centers as participants in the studies. The second, important for protocols involving patients with immunodeficiency diseases, has been to establish close collaborations with key members of the Pediatric Immunology group at the University of Washington/Children's Hospital and Regional Medical Center, who see and study many of these patients. The studies proposed under this Project have relevance for hematopoietic cell transplantation in patients with hemoglobinopathies, such as sickle cell disease and thalassemia major, autoimmune diseases, and those with malignant diseases, including myelodysplastic syndromes studied under Project 4 of this grant. Also, hematopoietic cell transplantation protocols, that are found to be both effective and safe for patients with hematologic diseases, might eventually be of interest in the treatment of recipients of solid organ grafts, e.g. kidney or lung. In that setting, a concurrent or preceding hematopoietic graft from the kidney or lung donor would provide an immunologic "platform" for the solid organ graft, which would be indefinitely accepted without the need for lifelong immunosuppression.