Patients who consented to the optional therapeutic window were randomized to receive upfront methotrexate over 4 or 24 hours. Four days after methotrexate treatment, remission induction therapy began with prednisone, vincristine, daunorubicin, and asparaginase (Table 1). Patients with ≥ 1% MRD on day 19 received three additional doses of asparaginase. Subsequent induction therapy consisted of cyclophosphamide, mercaptopurine and cytarabine. Upon hematopoietic recovery (between days 43 and 46), MRD was assessed, and consolidation therapy began (Table 1).