TY - JOUR
T1 - 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
T2 - A pediatric oncology group phase III trial
AU - Mahoney, Donald H.
AU - Shuster, Jonathan
AU - Nitschke, Ruprecht
AU - Lauer, Stephen J.
AU - Winick, Naomi
AU - Steuber, C. Philip
AU - Camitta, Bruce
PY - 1998/1
Y1 - 1998/1
N2 - Purpose: To determine whether early intensification with 12 courses of intravenous methotrexate and 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: Seven hundred nine patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction. Patients were randomized to receive intensification with either IVMTX 1,000 mg/m2 plus IVMP 1,000 mg/m2 (regimen A) or LDMTX 30 mg/m2 every 6 hours for six doses with IVMP 1,000 mg/m2 (regimen B). Twelve courses were 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 forty-nine were assigned to regimen A and 350 to regimen B. The estimated 4-year continuous complete remission (CCR) rate far patients treated 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, neurotoxicity, stomatitis, and hospitalizations were more frequent among patients treated on regimen A. Conclusion: Intensification with IVMTX/IVMP is more effective than LDMTX/IVMP for prevention of relapse in children with B-precursor ALL at lower risk for relapse.
AB - Purpose: To determine whether early intensification with 12 courses of intravenous methotrexate and 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: Seven hundred nine patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction. Patients were randomized to receive intensification with either IVMTX 1,000 mg/m2 plus IVMP 1,000 mg/m2 (regimen A) or LDMTX 30 mg/m2 every 6 hours for six doses with IVMP 1,000 mg/m2 (regimen B). Twelve courses were 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 forty-nine were assigned to regimen A and 350 to regimen B. The estimated 4-year continuous complete remission (CCR) rate far patients treated 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, neurotoxicity, stomatitis, and hospitalizations were more frequent among patients treated on regimen A. Conclusion: Intensification with IVMTX/IVMP is more effective than LDMTX/IVMP for prevention of relapse in children with B-precursor ALL at lower risk for relapse.
UR - http://www.scopus.com/inward/record.url?scp=0344333442&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344333442&partnerID=8YFLogxK
U2 - 10.1200/JCO.1998.16.1.246
DO - 10.1200/JCO.1998.16.1.246
M3 - Article
C2 - 9440749
AN - SCOPUS:0344333442
SN - 0732-183X
VL - 16
SP - 246
EP - 254
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 1
ER -