Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation

Allogeneic stem cell transplantation is the only treatment that can restore a normal hematopoiesis in Fanconi anemia (FA). In this retrospective multi center study, we analyzed the results of this approach using HLA-matched un related bone marrow donors, and tried to identify covariates predicting the outcome of the transplant. From January 1985 to June 1998, 69 FA patients were transplanted with unrelated HLA-matched donors. Patients' characterist ics before and after transplant were provided by the European group blood a nd marrow transplant registry and were analyzed in collaboration with the E uropean Fanconi Anemia Registry. The 3-year probability of survival was 33% . Extensive malformations, a positive recipient cytomegalovirus serology, t he use of androgens before transplant, and female donors were associated wi th a worse outcome. Primary graft failures were observed more frequently wh en female donors were used, mainly because the grafts contained lower nucle ated cell doses per kilogram of recipient body weight compared with grafts coming from male donors. The probability of grade III-IV acute graft-versus -host disease (GVHD) was 34%. Elevated serum alanine/aspartate transaminase s before transplantation; limb, urogenital tract, or nephrologic malformati ons; and non-T cell-depleted grafts were predictors of severe acute GVHD. T his study shows the dramatic impact of preexisting congenital malformations on the outcome of FA patients transplanted with HLA-matched unrelated dono rs. If the use of T-cell depletion has led to a dramatic reduction of acute GVHD incidence, no significant outcome improvement was observed with this approach, mainly because of an increased risk of graft failure. (Blood, 200 0;95:422-429) (C) 2000 by The American Society of Hematology.