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Shortening Infusion Time for High-Dose Methotrexate Alters Antileukemic Effects: A Randomized Prospective Clinical Trial
- Source :
- Mikkelsen, T S, Sparreboom, A, Cheng, C, Zhou, Y, Boyett, J M, Raimondi, S C, Panetta, J C, Bowman, W P, Sandlund, J T, Pui, C-H, Relling, M V & Evans, W E 2011, ' Shortening infusion time for high-dose methotrexate alters antileukemic effects : a randomized prospective clinical trial ', Journal of Clinical Oncology, vol. 29, no. 13, pp. 1771-8 . https://doi.org/10.1200/JCO.2010.32.5340
- Publication Year :
- 2011
- Publisher :
- American Society of Clinical Oncology (ASCO), 2011.
-
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 accumulation in hyperdiploid ALL (median: 3,919 v 2,417 pmol/109 cells, P = .0038); T-cell ALL exhibited smaller differences in MTXPG1-7 but greater antileukemic effects with the longer infusion (median decrease in leukemia cells: 88.4% v 51.8%, P = .0075). In contrast, infusion duration had no significant impact on MTXPG1-7 accumulation or antileukemic effects in ALL with the t(12;21)/(ETV6-RUNX1) chromosomal translocation. Conclusion Shortening the infusion time of HDMTX reduces accumulation of active methotrexate in leukemia cells and decreases antileukemic effects, with differing consequences among major ALL subtypes.
- Subjects :
- Antimetabolites, Antineoplastic
Cancer Research
Randomization
Adolescent
medicine.drug_class
Pharmacology
Antimetabolite
Drug Administration Schedule
law.invention
chemistry.chemical_compound
Randomized controlled trial
In vivo
law
hemic and lymphatic diseases
Humans
Medicine
business.industry
Infant
Precursor Cell Lymphoblastic Leukemia-Lymphoma
medicine.disease
Clinical trial
Leukemia
Methotrexate
Polyglutamic Acid
Oncology
chemistry
Purines
Child, Preschool
Antifolate
business
medicine.drug
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....a1426839fe315c602c80aafc98eaf0aa