Faculty Collaboration Database

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. J Clin Oncol 1998 Jan;16(1):246-54

Date

01/24/1998

Pubmed ID

9440749

DOI

10.1200/JCO.1998.16.1.246

Scopus ID

2-s2.0-0344333442 (requires institutional sign-in at Scopus site)   79 Citations

Abstract

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 I.V. 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 for 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.

Author List

Mahoney DH Jr, Shuster J, Nitschke R, Lauer SJ, Winick N, Steuber CP, Camitta B

Author

Bruce m. Camitta Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Oral
Antidotes
Antineoplastic Combined Chemotherapy Protocols
Burkitt Lymphoma
Child, Preschool
Female
Humans
Infusions, Intravenous
Leucovorin
Male
Mercaptopurine
Methotrexate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proportional Hazards Models
Remission Induction
Sex Factors
Treatment Failure