Intensification with intermediate-dose intravenous methotrexate is effective therapy for children with lower-risk B-precursor acute lymphoblastic leukemia: A Pediatric Oncology Group study. J Clin Oncol 2000 Mar;18(6):1285-94
Date
03/15/2000Pubmed ID
10715299DOI
10.1200/JCO.2000.18.6.1285Scopus ID
2-s2.0-0342445410 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
PURPOSE: To determine whether early intensification with 12 courses of intravenous (IV) methotrexate (MTX) and IV mercaptopurine (MP) is superior to 12 courses of IV MTX alone for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL).
PATIENTS AND METHODS: Six hundred fifty-one eligible patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction therapy. Patients were randomized to receive intensification with IV MTX 1,000 mg/m(2) plus IV MP 1,000 mg/m(2) (regimen A) or IV MTX 1,000 mg/m(2) alone (regimen C). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and triple intrathecal therapy every 12 weeks for 2 years.
RESULTS: Six hundred forty-five patients (99.1%) achieved remission. Three hundred twenty-five were assigned to regimen A and 320 to regimen C. The estimated 4-year overall continuous complete remission for patients treated with regimen A is 82.1% (SE = 2.4%) and for regimen C is 82.2% (SE = 2.6%; P =.5). No significant difference in overall outcome was shown by sex or race. Serious grade 3/4 neurotoxicity, principally characterized by seizures, was observed in 7.6% of patients treated with either regimen.
CONCLUSION: Intensification with 12 courses of IV MTX is an effective therapy for prevention of relapse in children with B-precursor ALL who are at lower risk for relapse but may be associated with an increased risk for neurotoxicity. Prolonged infusions of MP combined with IV MTX did not provide apparent advantage.
Author List
Mahoney DH Jr, Shuster JJ, Nitschke R, Lauer S, Steuber CP, Camitta BMESH terms used to index this publication - Major topics in bold
Antimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy Protocols
Child
Child, Preschool
Drug Administration Schedule
Female
Humans
Infant
Infusions, Intravenous
Male
Mercaptopurine
Methotrexate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proportional Hazards Models
Survival Analysis
