Association between delayed methotrexate metabolism, coagulation function, and adverse reactions in patients with...

This 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.

A 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.

Significant 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.

Delayed 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.