Risk factors for high‐dose methotrexate associated toxicities in patients with primary central nervous system lymphoma

WHAT IS KNOWN AND OBJECTIVE: Methotrexate (MTX) is an antimetabolic antitumor drug with high individual differences and may lead to severe toxicities in a considerable number of patients. This study aimed to explore the factors influencing major adverse events in patients with primary central nervous system lymphoma treated with high-dose MTX (HD-MTX), which could be useful in clinical practice. METHODS: between January 2015 and December 2016 were enrolled in this study. We assessed the association between clinical characteristics, MTX pharmacokinetics, MTX delayed elimination, and adverse events, including hepatotoxicity, acute kidney injury (AKI), and myelosuppression. RESULTS AND DISCUSSION: ; OR = 0.808, 95% CI 0.711-0.917, p = 0.001, respectively). Patient's age, eGFR before MTX infusion, and co-administration of vindesine had a significant effect on AKI (OR = 0.960, 95% CI 0.935-0.986, p = 0.003; OR = 1.009, 95% CI 1.001-1.017, p = 0.034; OR = 5.463, 95% CI 1.793-16.646, p = 0.003, respectively). LDH and Co-administration of vindesine had a significant effect on myelosuppression (OR = 0.985, 95% CI 0.972-0.998, p = 0.025; OR = 3.070, 95% CI 1.032-9.133, p = 0.044). WHAT IS NEW AND CONCLUSION: Our study demonstrated that co-administration of VDS, eGFR before MTX infusion, and the baseline index of laboratory examinations including ALT, WBC, LDH may be useful biomarkers for predicting MTX-induced toxicities.