Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia: Results of Children's Oncology Group trial P9906

Abstract

Background: The augmented BFM regimen improves outcome for children with NCI high acute lymphoblastic leukemia (ALL). Patient age, sex, and presenting white blood cell count (WBC) can be used to identify a subset of approximately 12% of children with B-precursor ALL that had a 5-year continuous complete remission (CCR) rate of only about 50% on earlier Pediatric Oncology Group (POG) trials. Procedures: Children's Oncology Group trial P9906 evaluated a modified augmented BFM regimen in 267 patients with particularly high risk B-precursor ALL. Minimal residual disease (MRD) was assessed in blood at day 8 and in marrow at day 29 of induction and correlated with outcome. Results: The 5-year CCR probability for patients in P9906 was significantly better than that observed for similar patients on POG trials 8602/9006 (62.2±3.7% vs. 50.6±2.4%; P=0.0007) but similar to POG 9406 (63.5±2.4%; P=0.81). Interim analysis showed poor central nervous system (CNS) control, especially in patients with initial WBC ≥100,000/microliter. Day 29 marrow MRD positive (≥0.01%) vs. negative patients had 5 year CCR rates of 37.1±7.4% vs. 72.6±4.3%; day 8 blood MRD positive vs. negative patients had 5 year CCR rates of 57.1±4.6% vs.83.6±6.3%. End induction marrow MRD predicted marrow but not CNS relapse. In multivariate analysis, day 29 MRD>0.01%, initial WBC≥100,000/μl, male gender, and day 8 blood MRD>0.01% were significant prognostic factors. Conclusions: Augmented BFM therapy improved outcome for children with higher risk ALL. Day 8 blood and day 29 marrow MRD were strong prognostic factors in these patients. © 2011 Wiley-Liss, Inc.