Doses during continuation therapy were as follows: MP (mercaptopurine), 75 mg/m²/d; MTX (methotrexate), 40 mg/m²/wk; VP (etoposide), 300 mg/m²/wk; cyclo (cyclophosphamide), 300 mg/m²/wk; AraC (cytarabine), 300 mg/m²/wk; Pred (prednisone), 40 mg/m²/d; asparaginase (Elspar; Merck, West Point, PA), 10 000 IU/m²/wk; and dex (dexamethasone), 8 mg/m²/d. Patients at higher risk to develop central nervous system relapse received additional doses of intrathecal therapy along with cranial irradiation at 1800 cGy in 12 fractions over 2.5 weeks beginning at week 56; those with central nervous system leukemia at diagnosis received 2400 cGy in 16 fractions over 3 weeks beginning at week 56. Continuation therapy consisted of repeated 8-week cycles of the drugs listed above for a total of 120 weeks, except that (1) in both protocols, the HDMTX was replaced by MTX at 40 mg/m² after week 55; (2) in the intermediate/high-risk arm of Total XIIIA, reinduction therapy was given at week 32–38, and asparaginase was omitted after reinduction; and (3) in both arms of Total XIIIB, reinduction therapy was given at weeks 16 to 21.