Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2011
Shortening infusion time for high-dose methotrexate alters antileukemic effects: a randomized prospective clinical trial.
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- Association of GATA3 Polymorphisms With Minimal Residual Disease and Relapse Risk in Childhood Acute Lymphoblastic Leukemia.Journal of the National Cancer Institute · 2021Trial
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- Trial
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- Effect of high-dose methotrexate infusion duration on 48-hour drug levels and toxicity in children with acute lymphoblastic leukaemia: a quality-of-care study.Cancer chemotherapy and pharmacology · 2026Observational
- Neurotoxic effects of the chemotherapeutic drug "methotrexate": a literature review.Annals of medicine and surgery (2012) · 2025Review
- Cellular pharmacokinetic of methotrexate and its modulation by folylpolyglutamate synthetase and γ-glutamyl hydrolase in tumor cells.PloS one · 2024Article
- The Rate of Infusion Represents an Important Aspect of Administering Anticancer Agents.Risk management and healthcare policy · 2023Review
- Early clinical indicators of acute kidney injury caused by administering high-dose methotrexate therapy to juvenile pigs.Frontiers in nephrology · 2023Article
- Studies on the intracellular accumulation process of methotrexate and its correlation with the key protein using an LC-MS/MS method: a novel way to realize prospective individualized medication.Analytical and bioanalytical chemistry · 2021Article
- New insights into methotrexate accumulation in leukemia cellsMolecular & cellular oncology · 2021Article
- Pharmacogenomics of intracellular methotrexate polyglutamates in patients' leukemia cells in vivo.The Journal of clinical investigation · 2020Article
- Glutamic Acid Increased Methotrexate Polyglutamation and Cytotoxicity in a CCRF-SB Acute Lymphoblastic Leukemia Cell Line.Medicina (Kaunas, Lithuania) · 2019Article
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- Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia.The pharmacogenomics journal · 2015Article
- Survival of Mexican Children with Acute Lymphoblastic Leukaemia under Treatment with the Protocol from the Dana-Farber Cancer Institute 00-01.BioMed research international · 2015Article
- High-dose methotrexate in Egyptian pediatric acute lymphoblastic leukemia: the impact of ABCG2 C421A genetic polymorphism on plasma levels, what is next?Journal of cancer research and clinical oncology · 2014Article
- Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014Article
- Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments.Cancer chemotherapy and pharmacology · 2013Article
- A 50-year journey to cure childhood acute lymphoblastic leukemia.Seminars in hematology · 2013Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeTo determine whether shortening the infusion duration of high-dose methotrexate (HDMTX; 1 g/m(2)) affects the in vivo accumulation of active methotrexate polyglutamates (MTXPG(1-7)) in leukemia cells and whether this differs among major acute lymphoblastic leukemia (ALL) subtypes.
methodsFrom June 2000 through October 2007, 356 children with ALL were randomly assigned to receive initial single-agent treatment with HDMTX (1 g/m(2)) 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 MTXPG(1-7) 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).
resultsThe 24-hour infusion resulted in significantly higher amounts of MTXPG(1-7) in bone marrow leukemia cells (median: 1,695 v 1,150 pmol/10(9) cells, P = .0059), and better antileukemic effects. The 24-hour infusion had the greatest effect on MTXPG(1-7) accumulation in hyperdiploid ALL (median: 3,919 v 2,417 pmol/10(9) cells, P = .0038); T-cell ALL exhibited smaller differences in MTXPG(1-7) 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 MTXPG(1-7) accumulation or antileukemic effects in ALL with the t(12;21)/(ETV6-RUNX1) chromosomal translocation.
conclusionShortening the infusion time of HDMTX reduces accumulation of active methotrexate in leukemia cells and decreases antileukemic effects, with differing consequences among major ALL subtypes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.