Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide

Marrow-ablative chemo-radiotherapy followed by hematopoietic stem cell resc ue from an allogeneic source improves outcomes for children with high-risk acute leukemia. The first effective pre-transplant preparative regimens con sisted of high-dose cyclophosphamide (CY) and total body irradiation (TBI), Subsequent attempts have been made to improve leukemia-free survival, by a dding other chemotherapy agents to these agents. In previous clinical studi es of total body irradiation, etoposide, cyclophosphamide (TBI-VP-16-Cy) in adult allogeneic bone marrow transplantation, there has been a high incide nce of severe regimen-related toxicity, In this study, we investigated the safety and efficacy of this combination in 41 children who received TBI (12 -14 Gy), VP-16 (30 mg/kg), and CY (60 mg/kg x 2) and then either matched si bling or alternative donor transplants for acute leukemia. There was only o ne case of fatal regimen-related toxicity. The estimated 3-year event-free survival for patients with early or intermediate stage disease was 68% (53- 88%), The estimated event-free survival of patients with advanced disease w as 17% (5-59%), TBI-VP16-CY is safe in pediatric transplantation, and it ha s good efficacy for transplant recipients with less advanced disease.