Genetic Randomization to Allogeneic Bone Marrow Transplant in First Remission Pediatric Acute Myeloid Leukemia Patients, Pediatric Oncology Group 9421 (Now Childrens Oncology Group).

The role of allogeneic bone marrow transplant (BMT) in pediatric patients (pts) with de novo AML in first complete remission remains controversial. One of the objectives of POG 9421, a phase 3 trial for children with newly diagnosed AML, was to compare the disease free survival between pts genetically randomized between allogeneic BMT and consolidation chemotherapy. All pts enrolled on POG 9421 were randomized to standard dose (SD) ara-C or high dose (HD) ara-C during course 1 of induction prior to knowing if there was an HLA matched (5/6 or 6/6) sibling that might be a potential marrow donor. The intent of the study was for pts who achieved a CR and had an HLA matched sibling and did not have Down syndrome (DS) to receive a BMT following the second course of induction. The protocol preparative regimen included TBI (1200 cGy at 150 cGy bid for 4 days) and high dose etoposide (60 mg/kg iv over 4 hours on day -3). GVHD prophylaxis utilized methotrexate and cyclosporine. Six hundred and fifty-four patients were registered on POG 9421, and 32 were ineligible due to wrong diagnosis or major protocol violation and 57 had DS. Five hundred and one of 560 evaluable pts achieved a CR and were eligible for transplant if a matched sibling donor was identified. 83/501 or 16.5% of the patients had a donor and proceeded to transplant and were eligible for evaluation. Of the 83 pts, 39 received SD ara-c for induction and 44 received HD ara-c for induction. The median times from registration to CR were 39.0 days and 33.0 days, and the median times from CR to transplant were 39.0 days and 46.5 days for SD and HD ara-c, respectively. Twenty-nine of 83 pts had post BMT events including 10 deaths from toxicity, 18 relapses, and 1 second malignancy. Of the 29 events, 6 deaths and 6 relapses occurred in the SD arm and 4 deaths, 12 relapses, and 1 secondary malignancy in the HD arm. The 3yr DFS of patients who received SD ara-c induction was 71.8 +/− 7.6%, and was not significantly different from that of HD ara-c induction (3-year DFS 63.3 +/− 8.2%, p=0.49). Seven deaths occurred within 100 days of transplant. The rates of patients off protocol therapy due to event in cytogenetic subgroups are as follows: 7/25 for patients with normal cytogenetics; 3/10 for patients with 11q23 abnormalities; 6/13 for patients with t(8;21), and 7/18 for patients with miscellaneous abnormalities; there were no events during the protocol therapy among the 6 patients with inv16. The 3-year DFS and 3-year overall survival for the 83 transplanted patients were 67.3 +/− 5.6% and 69.7 +/− 5.4%, respectively. The DFS for the transplanted patients was superior to consolidation chemotherapy (N=418, 3-year DFS=37.5+/− 2.7%, p<0.001). Five pts had GVHD, 2 with grade 3, 2 with grade 2, and 1 with grade 1. Conclusion: Patients were able to receive their transplants within the goal of 8 weeks of induction II. The outcome of BMT was superior to consolidation chemotherapy as has been reported by other groups. The ara-c schedule had no significant impact on the outcome. The reported low incidence of GVHD in this study prevents us from evaluating its impact on outcome.