Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia

Overview

Based on success in other diseases, the Fred Hutchinson Cancer Research Center (FHCRC) has developed a transplant procedure for Fanconi anemia (FA), which does not completely destroy the patient's remaining bone marrow. It should also be less harmful (toxic). Researchers wish to test whether this approach can overcome the graft failure often seen when bone marrow or peripheral blood stem cells from an unrelated donor are used. Researchers also will look at whether the procedure is less toxic than a conventional bone marrow transplant (BMT).

PRIMARY OBJECTIVES: I. To determine whether donor chimerism can be achieved in patients with Fanconi anemia receiving marrow or peripheral blood stem cell (PBSC) grafts from unrelated donors following low dose total body irradiation (TBI), fludarabine (fludarabine phosphate), mycophenolate mofetil, and cyclosporine. II. To determine the lowest dose of TBI necessary to achieve donor chimerism in at least 80% of patients. III. To determine the incidence of severe regimen-related toxicity. SECONDARY OBJECTIVES: I. To determine the survival of Fanconi anemia patients transplanted with unrelated donor marrow or PBSC grafts after conditioning with a non-myeloablative regimen. II. To determine the incidence and severity of graft-vs-host disease (GVHD) incurred with unrelated bone marrow or PBSC grafts transplant patients with Fanconi anemia. III. To determine if mixed chimerism results in amelioration of symptoms associated with bone marrow failure in patients with Fanconi anemia. OUTLINE: NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96. After completion of study treatment, patients are followed up at 6 months and annually thereafter.