Improved Survival Following HLA-Matched Related Marrow Transplantation in Pediatric Patients with Severe Aplastic Anemia: (A 39-Year Retrospective Analysis)

Allogeneic marrow transplantation offers curative therapy for pediatric patients with severe aplastic anemia. Over the past 4 decades, significant improvements in the long term outcome of patients treated with allogeneic marrow grafts have resulted from progress in the prevention and treatment of graft rejection and graft-versus-host disease (GVHD). Here we report the outcome of 149 pediatric patients, ages 2-19 years who received HLA-matched related marrow grafts for treatment of severe aplastic anemia between 1971 and 2009. Patients were divided into 3 groups, reflecting changes in conditioning and GVHD prophylaxis regimens that occurred over time. Group 1 consisted of 100 patients who were conditioned with Cyclophosphamide (CY; 200 mg/kg) followed by “long” (102 days) Methotrexate (MTX) for GVHD prevention. Group 2 consisted of 19 patients who received CY followed by “short” (days 1, 3, 6, and 11) MTX and cyclosporine (CSP; through day 180). Group 3 consisted of 30 patients who were conditioned with CY and horse antithymocyte globulin (ATG) followed by MTX and CSP for GVHD prevention. The risk of mortality was significantly different between the 3 groups (p < 0.0001). With a median follow up of 25.2 (range, 0.3-37) years, the 5-year survival estimates were 66% for group 1, 95% for group 2, and 100% for group 3. There was a suggestion that the risk of rejection was different between the 3 groups (p = 0.06) and the 3-year estimates of graft rejection were 22%, 32%, and 12%, respectively. The estimated probabilities of grades III-IV acute GVHD were 15% for group 1, 0% for group 2, and 3% for group 3. The 2-year estimates of chronic GVHD were 21%, 21%, and 7%, respectively. In summary, advances in conditioning and GVHD prophylaxis regimens as well as supportive care during the past 39 years have led to improved outcomes for pediatric patients with severe aplastic anemia. These results strongly support the use of allogeneic marrow transplantation for newly diagnosed pediatric patients with severe aplastic anemia who have an HLA-matched related donor. Allogeneic marrow transplantation offers curative therapy for pediatric patients with severe aplastic anemia. Over the past 4 decades, significant improvements in the long term outcome of patients treated with allogeneic marrow grafts have resulted from progress in the prevention and treatment of graft rejection and graft-versus-host disease (GVHD). Here we report the outcome of 149 pediatric patients, ages 2-19 years who received HLA-matched related marrow grafts for treatment of severe aplastic anemia between 1971 and 2009. Patients were divided into 3 groups, reflecting changes in conditioning and GVHD prophylaxis regimens that occurred over time. Group 1 consisted of 100 patients who were conditioned with Cyclophosphamide (CY; 200 mg/kg) followed by “long” (102 days) Methotrexate (MTX) for GVHD prevention. Group 2 consisted of 19 patients who received CY followed by “short” (days 1, 3, 6, and 11) MTX and cyclosporine (CSP; through day 180). Group 3 consisted of 30 patients who were conditioned with CY and horse antithymocyte globulin (ATG) followed by MTX and CSP for GVHD prevention. The risk of mortality was significantly different between the 3 groups (p < 0.0001). With a median follow up of 25.2 (range, 0.3-37) years, the 5-year survival estimates were 66% for group 1, 95% for group 2, and 100% for group 3. There was a suggestion that the risk of rejection was different between the 3 groups (p = 0.06) and the 3-year estimates of graft rejection were 22%, 32%, and 12%, respectively. The estimated probabilities of grades III-IV acute GVHD were 15% for group 1, 0% for group 2, and 3% for group 3. The 2-year estimates of chronic GVHD were 21%, 21%, and 7%, respectively. In summary, advances in conditioning and GVHD prophylaxis regimens as well as supportive care during the past 39 years have led to improved outcomes for pediatric patients with severe aplastic anemia. These results strongly support the use of allogeneic marrow transplantation for newly diagnosed pediatric patients with severe aplastic anemia who have an HLA-matched related donor.