Risk factors for delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia and lymphoma.

Abstract

High-dose methotrexate (HD-MTX) therapy is widely used in patients with acute lymphoblastic leukemia (ALL) and lymphoma. However, some patients experience delayed MTX elimination, which requires treatment suspension or dose reduction to avoid organ damage. This single-center retrospective analysis reviewed the clinical data of 88 children with ALL or non-Hodgkin lymphoma who received a total of 269 courses of HD-MTX therapy between April 2008 and April 2019. HD-MTX was defined as MTX administration at 2.0, 3.0, or 5.0g/m2 over a 24-h period, and delayed MTX elimination was defined as a serum MTX concentration ≥ 1.0µmol/L at 48h after the start of HD-MTX. Clinical factors were compared between courses with and without delayed MTX elimination. MTX elimination was delayed in 21 of the 269 courses (7.8%). Multivariate analysis showed that first HD-MTX course (OR 4.04), lower urine volume per BSA on the first day of HD-MTX administration (< 2,675mL/m2, OR 5.10), higher total bilirubin (> 0.5mg/dL, OR 5.11), lower eGFR (< 136mL/min/1.73m2, OR 3.90), higher dose of MTX(> 3.0g/m2, OR 10.8), and lower urine volume per BSA on the next day of starting HD-MTX (< 2,107mL/m2, OR 3.43) were independent risk factors for delayed MTX elimination.