Predictors Associated with Delayed Methotrexate Clearance among Patients with Haematological Malignancies

Abstract

Introduction: High dose methotrexate is commonly utilised in haematological malignancies; however, the prevalence of delayed clearance is not well-defined. The study aimed to determine the prevalence of delayed clearance of methotrexate, to analyse correlation between rate of methotrexate infusions and its concentrations, and to identify the predictors associated with delayed clearance. Method: A crosssectional study was conducted among adult patients with haematological malignancies who received high-dose methotrexate. Spearman’s correlation was utilised to analyse correlation between the rates of methotrexate infusions with its concentrations at 48 and 72 hours. Multiple logistic regression was used to identify factors associated with delayed clearance. Results: A total of 63 patients with 159 methotrexate infusions were included, with a mean age of 42.2 years (±18.06) and a median body mass index of 23.36 kg/m2 (19.91-26.14). Delayed methotrexate clearance was observed in 29 (46%) patients, which affected 41 (25.6%) methotrexate infusions. A poor negative correlation was found between the rate of methotrexate infusion and 48-hour concentration (r=-0.206, p=0.009). Older age (odds ratio (OR) 1.06, 95% confidence interval (CI) 1.03-1.10, p3000 mg/m2 (OR 3.33, 95% CI 6.45-120.88, p<0.001) were identified as the predictors of delayed methotrexate clearance. Conclusion: Almost half of the patients experienced delayed methotrexate clearance. A slower rate of infusion was found to correlate with higher 48-hour concentrations. Older age and higher doses of methotrexate were identified as predictors for delayed clearance. Prospective study is needed with larger sample size to ensure generalisability of the outcomes.

Keywords

• methotrexate
• delayed clearance
• pharmacokinetics
• haematology
• leukaemia