ArticleCancer medicine2024
Clinical Risk Factors for High-Dose Methotrexate-Induced Oral Mucositis Following Individualized Dosing.
Article in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Vortioxetine mitigates methotrexate-induced oral mucosa injury via sirtuin 1 pathway and intrinsic apoptosis signaling.BMC oral health · 2026Article
- Unveiling the risk: A comprehensive analysis of drug-induced aphthous ulcers using real-world data from FAERS.Medicine · 2026Article
- Grade 4 Mucositis Secondary to Methotrexate Use in a Pediatric Patient With Stage IV Burkitt Lymphoma: A Case Report.Cureus · 2025Article
- Mechanisms of Total Glucosides of Paeony in Alleviating Methotrexate-Induced Liver Injury.Drug design, development and therapy · 2025Article
- Consensus on managing delayed methotrexate elimination in high-dose therapy: insights from the Middle East.Frontiers in oncology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
backgroundOral mucositis affects about 20% of children undergoing high-dose methotrexate (HDMTX) for acute lymphoblastic leukemia (ALL), despite existing management strategies. Personalized HDMTX dosing, adjusted by pharmacokinetics and leukemia risk, has reduced mucositis incidence, but variations still occur with similar 24-h methotrexate levels.
methodsThis retrospective study investigated risk factors for oral mucositis under individualized methotrexate protocols. Data from patients with ≥ Grade 2 oral mucositis (CTCAE v4.0) were analyzed from the St. Jude Children's Research Hospital total 16 trial. A 1:1 case-control matching method considered age, sex, risk classification, immunophenotype, and methotrexate course. McNemar's, Bowker's symmetry, and Wilcoxon signed-rank tests were used for statistical analyses. Risk factors for recurrent mucositis were identified in a case-only analysis.
resultsThe study found significant associations between methotrexate-induced mucositis and new-onset skin rashes (p = 0.0027), fever (p = 0.0016), neutropenic fever (p = 0.0008), lower absolute neutrophil count (p < 0.0001), acute kidney injury (AKI) (p = 0.0164), delayed methotrexate clearance (p = 0.0133), and higher 42-h methotrexate levels (p = 0.0179). In the standard/high-risk group, mercaptopurine dose was also linked to mucositis (p = 0.0495). Multivariable analysis showed that skin rashes (OR 6.5, p = 0.0016), fever (OR 2.8, p = 0.009), and neutropenia (OR 2.3, p = 0.0106) were independent risk factors for mucositis. Female sex (OR 7.12, p = 0.015) and AKI (OR 3.819, p = 0.037) were associated with recurrent mucositis.
conclusionsFever, skin rashes, AKI, delayed methotrexate clearance, and higher 42-h methotrexate levels were key risk factors for HDMTX-induced oral mucositis. Skin rashes, fever, and neutropenia were independent predictors, while female sex and AKI were linked to recurrent mucositis.
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