March 3, 2026

Influence of methylene tetrahydrofolate reductase polymorphisms and coadministration of antimetabolites on toxicity after high dose methotrexate

Key Points

Toxicity after high-dose methotrexate is heavily influenced by antimetabolite coadministration, increasing risks for multiple adverse effects.
High-intensity co-treatment substantially raises the odds of haematological toxicity and complications, with significant odds ratios reported.
Retrospective analysis of 656 HDMTX courses reveals substantial links between 6MP dosage alterations and toxicity outcomes in pediatric ALL.
Findings highlight that 6MP dose adjustments could potentially mitigate treatment-related toxicity in patients undergoing HDMTX.

Abstract

BACKGROUND AND OBJECTIVE: Through interruption of maintenance treatment with 6-mercaptopurine (6MP), toxicity after high-dose methotrexate (HDMTX) may compromise the efficiency of the treatment of children with acute lymphocytic leukaemia (ALL). We investigated the influence of polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene and coadministration of antimetabolites on post-HDMTX toxicity. METHODS: Toxicity was retrospectively analysed after 656 HDMTX courses administered to 88 paediatric ALL patients at a single treatment centre. RESULTS: High-dose methotrexate with high-intensity co-treatment (6MP 75 mg/m(2)/d + MTX 20 mg/m(2)/wk) was found associated with increased odds of haematological toxicity (OR's: 3.47-7.88; P's: Udgivelsesdato: 2008/11

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Influence of methylene tetrahydrofolate reductase polymorphisms and coadministration of antimetabolites on toxicity after high dose methotrexate

Key Points

Abstract

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