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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.