The relationship between urine output and time to methotrexate clearance in pediatric leukemia patients receiving high-dose methotrexate therapy

High-dose methotrexate (HD-MTX) is a cornerstone of pediatric acute lymphoblastic leukemia (ALL) treatment but poses a risk for delayed clearance and associated toxicities. While hydration is standard to enhance methotrexate (MTX) excretion, the relationship between urine output (UO) and time to MTX clearance remains underexplored. We conducted a retrospective study of pediatric ALL patients treated with HD-MTX at Chang Gung Memorial Hospital between August 2023 and February 2025. Patients were stratified into higher (H-UO) and lower urine output (L-UO) groups using a 5.0 mL/kg/hr cutoff. Clinical outcomes including time to MTX normalization, delayed MTX clearance, hospitalization duration, and use of adjunctive diuretics were analyzed. Thirty-nine patients were included. The H-UO group showed significantly faster MTX clearance (2.0 vs. 4.0 days, P = 0.0035), lower incidence of delayed clearance (18.2% vs. 70.6%, P = 0.0025), and shorter hospital stays (5.0 vs. 7.0 days, P = 0.019). Diuretic use was higher in the L-UO group, primarily as a reactive measure. No significant difference in MTX-related major toxicities was observed. Higher UO is associated with more efficient time to MTX clearance and shorter hospitalization in pediatric ALL patients receiving HD-MTX. Prospective studies are warranted to optimize supportive care protocols.