The Saudi experience in fludarabine-based conditioning regimens in patients with Fanconi anemia undergoing stem cell transplantation: excellent outcome in recipients of matched related stem cells but not in recipients of unrelated cord blood stem cells.

Low-dose cyclophosphamide (CY) is now considered the backbone of many of the conditioning regimens used in patients with Fanconi anemia undergoing allogeneic stem cell transplantation (SCT). To reduce the risk of rejection and improve results, CY is usually used in combination with other agents/modalities, such as antithymocyte globulin (ATG), busulfan, radiation, and, more recently, fludarabine (Flu). In this study, we used a uniform Flu-based conditioning regimen (ie, CY, Flu, ATG) in 26 pediatric patients with Fanconi anemia undergoing SCT. The median patient age at the time of SCT was 7.8 years, and the stem cell source was an HLA-matched related donor in 19 patients and partially HLA-matched unrelated cord blood in 7 patients. The CY, Flu, ATG regimen was well tolerated overall, with a remarkably low incidence of graft-versus-host disease and hemorrhagic cystitis. All 19 patients in the matched related donor group engrafted and were alive and transfusion-independent at a median follow-up time of 19 months, compared with only 2 of 7 patients in the unrelated cord blood group. We conclude that the combination of CY, Flu, and ATG in the doses used in this study is well tolerated, and that the proclaimed positive effect of adding Flu to the conditioning regimens of patients with Fanconi anemia undergoing SCT is most pronounced in recipients of HLA-matched related transplants. Its value in unrelated cord blood transplantation probably depends on other factors, such as the degree of HLA matching and the cell dose.