Unrelated donor bone marrow transplantation for Fanconi anemia

Patients with Fanconi anemia (FA) commonly develop bone marrow failure, which may evolve to myelodysplasia or acute myeloid leukemia (AML). Treatment of these patients is complicated by their marked hypersensitivity to DNA cross-linking agents. In this report we describe the results of allogeneic unrelated donor bone marrow transplantation in seven FA patients, using a low-dose cyclophosphamide (40 mg/kg) and TBI (400-450 cGy) conditioning regimen. Two patients had bone marrow failure with normal chromosomes and no dysplasia prior to transplant. The remaining five had clonal chromosomal abnormalities. One patient had refractory anemia with excess blasts in transformation and two had early AML with 20 and 25% blasts, respectively. Two patients died early (before day 28) without hematological evidence of engraftment, one of veno-occlusive disease and one of infection (fungal). Four of the remaining five patients achieved sustained engraftment after the first marrow infusion; one patient had secondary graft failure requiring repeat marrow infusion but subsequently achieved engraftment. Of five evaluable patients, three had mild (grades I-II) acute GVHD and two had grade IV GVHD, which was fatal in both cases. Two of three evaluable surviving patients have chronic GVHD controlled with immunosuppression. Three patients survive 9 months to 3 years post-unrelated donor BMT: two who had early leukemia and one with severe aplasia at the time of transplant. These data indicate that unrelated donor BMT can be performed successfully in FA patients using cyclophosphamide 40 mg/kg and TBI 400 to 450 cGy, even after evolution to early leukemia. However, significant problems with both GVHD and engraftment remain. Future studies will evaluate the role of T cell depletion in improving the results of unrelated donor marrow transplantation in FA patients.