HLA-matched related donor hematopoietic cell transplantation in 43 patients with Fanconi anemia conditioned with 60 mg/kg of cyclophosphamide.

Cells from Fanconi anemia (FA) patients are hypersensitive to alkylating agents and radiation traditionally used as conditioning regimens for marrow cell transplantation, and patients experience serious toxicities. To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning. Here, we report the results in 43 FA patients who received marrow transplantation from HLA-matched related donors (37 siblings and 6 other relatives). Conditioning consisted of 15 mg CY/kg/day for 4 days along with Mesna. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. Forty patients (93%) are alive with a median follow-up of 3.7 (range 0.6 to 7.9) years. One patient with primary graft failure was successfully retransplanted. Three of 4 patients with late graft failures were retransplanted, and 2 of those are alive; 1 died before a second marrow graft. Twelve patients including 3 with rejection had cytogenetic abnormalities in their marrow cells before transplantation. Acute grade II-III and chronic GVHD (aGVHD, cGVHD) were seen in 17% and 28.5% of patients, respectively. These results confirm and extend our previous observations that conditioning with 60 mg CY/kg allows for sustained engraftment of HLA-matched related marrow grafts in most FA patients and is associated with low toxicity, low incidences of aGVHD and cGVHD, and excellent long-term survival.