Shortening Infusion Time for High-Dose Methotrexate Alters Antileukemic Effects: A Randomized Prospective Clinical Trial
- 1 May 2011
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 29 (13), 1771-1778
- https://doi.org/10.1200/jco.2010.32.5340
Abstract
Purpose To determine whether shortening the infusion duration of high-dose methotrexate (HDMTX; 1 g/m2) affects the in vivo accumulation of active methotrexate polyglutamates (MTXPG1-7) in leukemia cells and whether this differs among major acute lymphoblastic leukemia (ALL) subtypes. Methods From June 2000 through October 2007, 356 children with ALL were randomly assigned to receive initial single-agent treatment with HDMTX (1 g/m2) as either a 24-hour infusion or a 4-hour infusion at two pediatric hospitals in the United States. The primary outcome measures were the accumulation of MTXPG1-7 in leukemia cells and the antileukemic effects (eg, inhibition of de novo purine synthesis in bone marrow ALL cells, and decrease in circulating ALL cells). Results The 24-hour infusion resulted in significantly higher amounts of MTXPG1-7 in bone marrow leukemia cells (median: 1,695 v 1,150 pmol/109 cells, P = .0059), and better antileukemic effects. The 24-hour infusion had the greatest effect on MTXPG1-7 accumulati...This publication has 40 references indexed in Scilit:
- Modeling Mechanisms of In Vivo Variability in Methotrexate Accumulation and Folate Pathway Inhibition in Acute Lymphoblastic Leukemia CellsPLoS Computational Biology, 2010
- Treating Childhood Acute Lymphoblastic Leukemia without Cranial IrradiationNew England Journal of Medicine, 2009
- Acquired variation outweighs inherited variation in whole genome analysis of methotrexate polyglutamate accumulation in leukemiaBlood, 2009
- Impact of the Methotrexate Administration Dose on the Need for Intrathecal Treatment in Children and Adolescents With Anaplastic Large-Cell Lymphoma: Results of a Randomized Trial of the EICNHL GroupJournal of Clinical Oncology, 2009
- In Vivo Response to Methotrexate Forecasts Outcome of Acute Lymphoblastic Leukemia and Has a Distinct Gene Expression ProfilePLoS Medicine, 2008
- Antimetabolite therapy for lesser-risk B-lineage acute lymphoblastic leukemia of childhood: a report from Children's Oncology Group Study P9201Blood, 2007
- Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trialThe Lancet, 2007
- Prospective analysis of TEL/AML1-positive patients treated on Dana-Farber Cancer Institute Consortium Protocol 95-01Blood, 2006
- Acute lymphoblastic leukemia with TEL-AML1 fusion has lower expression of genes involved in purine metabolism and lower de novo purine synthesisBlood, 2004
- A Proportional Hazards Model for the Subdistribution of a Competing RiskJournal of the American Statistical Association, 1999