INTERMEDIATE-DOSE INTRAVENOUS METHOTREXATE WITH INTRAVENOUS MERCAPTOPURINE IS SUPERIOR TO REPETITIVE LOW-DOSE ORAL METHOTREXATE WITH INTRAVENOUS MERCAPTOPURINE FOR CHILDREN WITH LOWER-RISK B-LINEAGE ACUTE LYMPHOBLASTIC-LEUKEMIA - A PEDIATRIC-ONCOLOGY-GROUP PHASE-III TRIAL

Purpose: To determine whether early intensification with 12 courses of intravenous methotrexate Find intravenous mercaptopurine (IVMTX/IVMP) is superior to 12 courses of repetitive, low-dose oral MTX with IV MP (LDMTX/IVMP) for prevention of relapse in children with lower-risk B- lineage acute lymphoblastic leukemia (ALL). Patients and Methods: Seve n hundred nine patients were entered onto the study Vincristine, predn isone, and asparaginase were used for remission induction, patients we re randomized to receive intensification with either IVMTX 1,000 mg/m( 2) plus IVMP 1,000 mg/m(2) (regimen A) or LDMTX 30 mg/m(2) every 6 hou rs for six doses with IVMP 1,000 mg/m(2) (regimen B), Twelve courses w ere administered at 2-week intervals, Triple intrathecal therapy (TIT) was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and TIT every 12 weeks for 2 years. Results: Six hundred ninety-nine (99%) patients achieved remission. Three hundred f orty-nine were assigned to regimen A and 350 to regimen B. The estimat ed 4-year continuous complete remission (CCR) rate for patients treate d with regimen A is 80.3% (SE = 2.9%) and with regimen B is 75.9% (SE = 3.1%). By log-rank analysis, regimen A demonstrated superior CCR (P = .013. Transient neutropenia/thrombocytopenia, bacterial sepsis, neur otoxicity, stomatitis, and hospitalizations were more frequent among p atients treated on regiment A. Conclusion: Intensification with IVMTX/ IVMP is more effective than LDMTX/IVMP for prevention of relapse in ch ildren with B-precursor ALL at lower risk for relapse. (C) 1998 by Ame rican Society of Clinical Oncology.