Allogeneic bone marrow transplantation for fourteen patients with severe aplastic anemia

Background: Bone marrow transplantation (BMT) is the best curative approach for younger patients with severe aplastic anemia (SAA). Major obstacles to success of allogeneic BMT include graft-versus-host disease (GVHD), graft rejection and treatment related toxicities. Experience with 14 SAA patients who received BMT is reported here. Methods: From December 1986 to May 1995, 14 patients with SAA were treated with BMT; 13 were allogeneic, and 1 was syngeneic. There were nine males and five females whose average age was 24.7 years (range 15-36 years). The median pretransplant disease duration was 93 days (range 7-610 days). Five patients were nontransfused before BMT. The pre-transplant conditioning regimen consisted of 200 mg/kg cyclophosphamide (CY) intravenously, divided over four consecutive days, followed by 300 cGy total-body irradiation (TBI) on the day before BMT. Two untransfused, one transfused patient and one syngeneic transplant received CY only as preconditioning. For GVHD prophylaxis, the 13 patients were given a combination of cyclosporine and a short course of methotrexate. Results: Of the 14 patients 11 were still alive 10 to 90 months later, with functional engraftment; the median survival of 39 months. There were three deaths including one with primary graft failure with intracranial hemorrhage, and two with delayed graft rejection and sepsis. The patient who received syngeneic BMT developed late graft failure six months post-transplant, but was successfully treated with a second BMT. Acute GVHD occurred among 5 of the 13 engrafted patients, only one of whom was Grade III clinically. Chronic GVHD was observed in 2 out of 10 evaluable patients. Conclusions: The combination of CY and TBI is an effective, well-tolerated conditioning regimen for BMT in patients with SAA. The acute GVHD rate was low in our patients receiving cyclosporine. BMT is the treatment-of-choice for patients under the age of 40 with SAA, for those with human leucocyte antigen (HLA)-identical siblings or an identical twin and particularly for those patients who have not received transfusion.