Faculty Collaboration Database

Intermediate-dose intravenous methotrexate and mercaptopurine therapy for non-T, non-B acute lymphocytic leukemia of childhood: a Pediatric Oncology Group study. J Clin Oncol 1989 Oct;7(10):1539-44

Date

10/01/1989

Pubmed ID

2778483

DOI

10.1200/JCO.1989.7.10.1539

Scopus ID

2-s2.0-0024343162 (requires institutional sign-in at Scopus site)   86 Citations

Abstract

Methotrexate (MTX) and mercaptopurine (MP) are the mainstays of continuation therapy for acute lymphocytic leukemia (ALL). These drugs are stored in tissues as active metabolites. Relapse in ALL might reflect failure to achieve adequate intracellular drug levels. Assured (parenteral) delivery of higher doses of MTX and MP should maximize tissue levels of these drugs by overcoming individual variations in absorption, metabolism, clearance, and compliance. Fifty-nine children with ALL at lower risk of relapse received 12 intensive MTX/MP courses immediately after 4 weeks of standard vincristine, prednisone, and asparaginase induction. Each 2-week intensive course included: MTX, 200 mg/m2 intravenous (IV) push then 800 mg/m2 IV over 24 hours on day 1; MP, 200 mg/m2 IV push then 800 mg/m2 IV over 8 hours on day 2; MTX, 20 mg/m2 intramuscularly on day 8; and MP, 50 mg/m2 orally daily on days 8 to 14. After the 6 months of intensive therapy, continuation therapy was weekly MTX/MP (as on days 8 to 14) for 1 or 2 years. Age-based MTX was given intrathecally (IT) for CNS prophylaxis. All patients entered remission. Three patients relapsed: bone marrow (at 24 and 37 months), and bone marrow and CNS (at 34 months). There were no isolated CNS relapses or deaths in remission. Event-free survival at 4 years is 94% (SE, 7%) by Kaplan-Meier analysis. Toxicities (infection, mucositis) occurred in less than 10% of intensive MTX/MP courses. However, a child with Down's syndrome withdrew after three courses because of recurrent severe mucositis. Further studies of this regimen are in progress.

Author List

Camitta B, Leventhal B, Lauer S, Shuster JJ, Adair S, Casper J, Civin C, Graham M, Mahoney D, Munoz L

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

Antineoplastic Combined Chemotherapy Protocols
Child
Child, Preschool
Female
Follow-Up Studies
Humans
Infant
Infusions, Intravenous
Male
Mercaptopurine
Methotrexate
Neoplasm Recurrence, Local
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Remission Induction
Seizures