ArticleAmerican journal of translational research2025
Association between delayed methotrexate metabolism, coagulation function, and adverse reactions in patients with acute lymphoblastic leukemia receiving high-dose methotrexate treatment.
Article in American journal of translational research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Toxicity-Tailored Thresholds of Delayed Methotrexate Elimination in Non-Hodgkin Lymphoma: A Population-Based Approach to Therapy Optimization.European journal of drug metabolism and pharmacokinetics · 2026Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThis study aimed to identify the risk factors associated with delayed drug metabolism during high-dose methotrexate (HD-MTX) therapy and to analyze the relationship between delayed metabolism and post-treatment toxic adverse effects.
methodsA retrospective analysis was performed on 189 patients with acute lymphoblastic leukemia who received HD-MTX therapy at Xi'an Gaoxin Hospital between February 2018 and May 2023. Serum MTX concentrations were measured at 24, 48, and 72 hours after each HD-MTX administration (cycle), with a 48-hour concentration ≥ 1 μmol/L defining delayed metabolism on a per-cycle basis. Clinical characteristics and laboratory parameters were collected, and univariate and multivariate logistic regression analyses were conducted using SPSS version 27.00 and R version 4.3.3 to determine the risk factors for delayed metabolism. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of each significant factor.
resultsSignificant differences were observed between the delayed cycles (n = 105) and the non-delayed cycles (n = 450) across several clinical and laboratory variables, including age, body mass index (BMI), MTX dosage, activated partial thromboplastin time (APTT), and D-dimer (DD). Logistic regression analysis identified age, BMI, body surface area, MTX dosage, APTT, fibrinogen, DD, albumin, creatinine clearance rate, and phosphorus levels as independent risk factors for delayed metabolism. ROC curve analysis demonstrated that DD exhibited high predictive accuracy for delayed metabolism (area under the curve = 0.833). Moreover, delayed metabolism was significantly associated with a higher incidence of treatment-related toxicities, including mucosal injury, myelosuppression, renal impairment, and gastrointestinal reactions.
conclusionDelayed MTX metabolism is influenced by multiple clinical and biochemical factors, with DD emerging as a key predictor. Patients experiencing delayed metabolism are at greater risk for severe treatment-related toxicities. Clinicians should closely monitor these high-risk patients and consider timely preventive or corrective interventions to mitigate adverse outcomes.
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