- Protocol M: Patients receive oral mercaptopurine once daily on days 1-56 and high-dose methotrexate IV continuously over 24 hours, and methotrexate IT on days 8, 22, 36, and 50. Patients also receive leucovorin calcium IV 42, 48, and 54 hours after the start of high-dose methotrexate infusion. Patients are then stratified according to stage of disease (I or II vs III or IV). Patients with stage I or II disease proceed directly to maintenance therapy 2 weeks after completion of protocol M. Patients with stage III or IV disease proceed to the re-induction phase 2 weeks after completion of protocol M.