BONE-MARROW TRANSPLANTATION IN PEDIATRIC-PATIENTS WITH SEVERE APLASTIC-ANEMIA - CYCLOPHOSPHAMIDE AND ANTI-THYMOCYTE GLOBULIN CONDITIONING FOLLOWED BY RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATINGFACTOR

Purpose: Graft rejection remains a serious problem in patients transpl anted for severe aplastic anemia. Although additional immunosuppressio n with irradiation may decrease graft failure, significant sequelae ma y 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 accel erate myeloid recovery, GM-CSF was used posttransplant. Patients and M ethods: Twelve patients, with a median age of 3 years underwent BMT fr om HLA identical sibling (n = 11) or syngeneic (n = 1) donors. Conditi oning was cyclophosphamide 50 mg/kg x 4 days and anti-thymocyte globul in 30 mg/kg x 3 days. GM-CSF was administered at 10 mu g/kg until a ne utrophil 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, 50 0/mu l, and 1,000/mu l were 12, 13, and 15 days, respectively. Acute G VHD of less than or equal to grade II occurred in four patients; one p atient had grade III. This has resolved in all but one. Conclusion: Th e nonradiation conditioning regimen of cyclophosphamide/ATG appears to achieve durable engraftment in transfused children with matched sibli ng donors. GM-CSF may accelerate myeloid recovery without exacerbating GVHD, but its contribution to allogeneic transplant required further study.