Bone marrow transplantation in pediatric patients with severe aplastic anemia: Cyclophosphamide and anti-thymocyte globulin conditioning followed by recombinant human granulocyte-macrophage colony stimulating factor

Purpose: Graft rejection remains a serious problem in patients transplanted for severe aplastic anemia. Although additional immunosuppression with irradiation may decrease graft failure, significant sequelae may ensue. We evaluated a nonirradiation containing conditioning regimen for children with severe aplastic anemia with matched sibling donors utilizing cyclophosphamide and anti-thymocyte globulin (ATG). To accelerate myeloid recovery, GM-CSF was used posttransplant. Patients and Methods: Twelve patients, with a median age of 3 years underwent BMT from HLA identical sibling (n = 11) or syngeneic (n = 1) donors. Conditioning was cyclophosphamide 50 mg/kg x 4 days and anti-thymocyte globulin 30 mg/kg x 3 days. GM-CSF was administered at 10 mu g/kg until a neutrophil count of 1,000 was achieved. Cyclosporine alone was used for graft-versus-host disease prophylaxis. Results: All patients achieved durable engraftment at follow-up of 5-51 + months, with the exception of the identical twin. Median lime to neutrophil counts > 200/mu l, 500/mu l, and 1,000/mu l were 12, 13, and 15 days, respectively. Acute GVHD of less than or equal to grade II occurred in four patients; one patient had grade III. This has resolved in all but one. Conclusion: The nonradiation conditioning regimen of cyclophosphamide/ATG appears to achieve durable engraftment in transfused children with matched sibling donors. GM-CSF may accelerate myeloid recovery without exacerbating GVHD, but its contribution to allogeneic transplant required further study.