Double-delayed intensification improves event-free survival for children with intermediate-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group.

Addition of a delayed-intensification (DI) phase after standard induction/consolidation therapy was previously shown to improve outcome for patients younger than 10 years of age with intermediate-risk acute lymphoblastic leukemia (ALL). The current trial randomized 1204 patients to regimens containing a single DI phase (405 patients), 2 DI phases (DDI) (402 patients), or a single DI phase in conjunction with increased vincristine and prednisone pulses during maintenance (DIVPI) (397 patients). Estimates of event-free survival (EFS) and survival at 6 years are 79% ± 1% and 89% ± 1%, respectively. EFS was improved on DDI compared with either DI (log-rank P  = .04; Kaplan-Meier [KM] P  = .04; relative risk [RR] = 1.38) or DIVPI (log-rank P  = .04; KM P  = .01; RR = 1.39).There was no difference in EFS for the DI and DIVPI regimens (log-rank P  = .96; KM P  = .75). Survival estimates at 6 years were 87% (SD = 2%) for DI; 91% (SD = 2%) for DDI; and 90% (SD = 2%) for DIVPI ( P  = .17). Significant univariate risk factors for the overall cohort included poor day-7 marrow response, black race, and age of at least 5 years. These data demonstrate that DDI improves EFS of patients younger than 10 years of age with intermediate-risk ALL.