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 hypersensit ivity to DNA cross-linking agents, In this report we describe the resu lts of allogeneic unrelated donor bone marrow transplantation in seven FA patients, using a low-dose cyclophosphamide (40 mg/kg) and TBI (40 0-450 cGy) conditioning regimen. Two patients had bone marrow failure with normal chromosomes and no dysplasia prior to transplant. The rema ining five had clonal chromosomal abnormalities. One patient had refra ctory anemia with excess blasts in transformation and two had early AM L with 20 and 25% blasts, respectively. Two patients died early (befor e day 28) without hematological evidence of engraftment, one of veno-o cclusive disease and one of infection (fungal). Four of the remaining five patients achieved sustained engraftment after the first marrow in fusion; one patient had secondary graft failure requiring repeat marro w infusion but subsequently achieved engraftment. Of five evaluable pa tients, three had mild (grades I-II) acute GVHD and two had grade IV G VHD, which was fatal in both cases. Two of three evaluable surviving p atients have chronic GVHD controlled with immunosuppression. Three pat ients survive 9 months to 3 years post-unrelated donor BMT: two who ha d early leukemia and one with severe aplasia at the time of transplant . These data indicate that unrelated donor BMT can be performed succes sfully in FA patients using cyclophosphamide 40 mg/kg and TBI 400 to 4 50 cGy, even after evolution to early leukemia. However, significant p roblems with both GVHD and engraftment remain. Future studies will eva luate the role of T cell depletion in improving the results of unrelat ed donor marrow transplantation in FA patients.