Children's Cancer Group CCG-1882 improved outcome for 1-21-year old with high risk acute lymphoblastic leukemia and Induction Day 8 marrow blasts ≥25% (slow early responders, SER) with longer and stronger post induction intensification (PII). This CCG-1961 explored alternative PII strategies. We report 10-year follow-up for patients with rapid early response (RER) and for the first time details our experience for SER patients. A total of 2057 patients were enrolled, and 1299 RER patients were randomized to 1 of 4 PII regimens: standard vs. augmented intensity and standard vs. increased length. At the end of interim maintenance, 447 SER patients were randomized to idarubicin/cyclophosphamide or weekly doxorubicin in the delayed intensification phases. The 10-year EFS for RER were 79.4 ± 2.4% and 70.9 ± 2.6% (hazard ratio = 0.65, 95% CI 0.52-0.82, p < 0.001) for augmented and standard strength PII; the 10-year OS rates were 87.2 ± 2.0% and 81.0 ± 2.2% (hazard ratio = 0.64, 95% CI 0.48-0.86, p = 0.003). Outcomes remain similar for standard and longer PII, and for SER patients assigned to idarubicin/cyclophosphamide and weekly doxorubicin. The EFS and OS advantage of augmented PII is sustained at 10 years for RER patients. Longer PII for RER patients and sequential idarubicin/cyclophosphamide for SER patients offered no advantage. CCG-1961 is the platform for subsequent COG studies.