Successful engraftment without radiation after fludarabine-based regimen in fanconi anemia patients undergoing genotypically identical donor hematopoietic cell transplantation

Background. To potentially reduce late effects of malignancy, chronic graft-versus-host disease (GVHD), endocrinopathy, and infertility in patients with Fanconi anemia (FA) undergoing HLA-matched related donor hematopoietic cell transplantation (HCT), we developed a regimen using fludarabine (FLU), cyclophosphamide (CY), and anti-thymocyte globulin (ATG) followed by infusion of T-cell depleted (TCD) bone marrow (BM) or unmanipulated umbilical cord blood (UCB). GVHD prophylaxis consisted of cyclosporine and short course methylprednisolone. Procedure. Between April 2000 and June 2003, 11 patients (10 aplastic anemia (AA), 1 myelodysplastic syndrome (MDS)) underwent HCT using this regimen. Stem cell sources were BM and UCB in eight and three patients, respectively. Results. All patients demonstrated primary engraftment. Median days to neutrophil and platelet engraftment were 11 days (range 9-21) and 38 days (range 19-381), respectively. No patient developed GVHD after primary HCT. The patient with MDS relapsed with AML and a maternal donor recipient experienced secondary graft failure. For the nine FA patients with AA who underwent HLA-identical sibling donor HCT, the Kaplan-Meier estimates of overall survival and event-free survival (EFS) at 2 years are 1 00% and 82%, respectively, at a median follow-up of 2.9 years (range 1.9-4.8). Conclusions. In summary, a FLU-based, non-irradiation approach is effective for FA patients with AA undergoing HLA-identical sibling donor HCT.