Abstract

Objective: To describe acute toxicities of high-dose methotrexate (HD-MTX) and analyze factors associated with delayed methotrexate clearance in pediatric patients with osteosarcoma at the Vietnam National Children's Hospital (VNCH).

Methods: A retrospective descriptive study was conducted on 42 children aged 6-16 years diagnosed with osteosarcoma and treated with HD-MTX (12 g/m², maximum 20 g) from January 2018 to December 2023.

Results: The median age was 10 years; the male-to-female ratio was 1.1:1. A total of 427 MTX treatment courses were administered, with MTX levels available in 393 courses. The median MTX clearance time was 72 hours (range: 48-336 hours); MTX concentrations at 24, 48, and 72 hours were 3.9, 0.3, and 0.1 µmol/L, respectively. Timely clearance (≤72 hours) occurred in 280/393 courses (71.2%), while delayed MTX clearance (>72 hours) occurred in 113/393 courses (28.8%). MTX levels exceeded expected thresholds in 9.6% of courses; creatinine elevation occurred in 1.1%. Elevated SGOT and SGPT were observed in 65.8% and 79.0% of courses, respectively. Decreased neutrophil count, hemoglobin, and platelet count were observed in 38.5%, 63.1%, and 5.9% of courses, respectively. Age was significantly associated with delayed MTX clearance (OR = 1.297; 95% CI: 1.082-1.555; p = 0.005). Post-surgical MTX treatment showed a trend toward association but did not reach statistical significance (OR = 0.611; 95% CI: 0.368-1.105; p = 0.057).

Conclusion: HD-MTX in the treatment of pediatric osteosarcoma commonly causes hepatic and hematologic toxicities. Hematologic toxicities were mainly mild to moderate. Delayed MTX clearance occurred in 28.8% of treatment courses and was associated with older age.