Background: High-dose methotrexate is widely used in chemotherapy for malignant tumors. This study explores the correlation between methotrexate (MTX) and 7-hydroxy methotrexate (7-OHMTX) concentrations and indicators of liver and kidney function while evaluating the predictive value of MTX and 7-OHMTX levels for delayed elimination. Methods: The authors collected 372 blood samples from 107 leukemia or lymphoma patients (45 adults and 62 children) treated with high-dose methotrexate. The free and total concentrations of MTX and 7-OHMTX were measured 48, 72, or 96 hours after chemotherapy administration. SPSS 27 software was used to analyze the Spearman correlation between concentration and liver and kidney indicators. The nonparametric Mann–Whitney U test was used to compare the Normal and Delayed groups. Receiver operating characteristic curve analysis identified the threshold for delayed elimination. Results: The total 7-OHMTX concentration did not correlate with creatinine clearance (CCR) and creatinine (CR) in children. The free 7-OHMTX concentration showed a significant negative correlation with CCR ( P < 0.01) and a positive correlation with CR ( P < 0.01) in children and in subgroup A 2 (7–12 years). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly negatively correlated with both total and free 7-OHMTX/MTX concentrations in children ( P < 0.01). MTX and 7-OHMTX concentrations showed no correlation with CR, CCR, AST, or ALT in adult patients. Conclusions: Clinicians should closely monitor patients for signs of elimination delay when free 7-OHMTX concentrations exceed 0.081 μmol/L 48 hours or later. Incorporating free-concentration monitoring predicts hepatotoxicity and nephrotoxicity in children more accurately than total concentrations alone, facilitating timely clinical intervention and ensuring patient safety.
Gao et al. (Fri,) studied this question.