소아 급성림프모구백혈병 및 비호지킨림프종 환자에서 고용량 methotrexate 투여 후 배설지연

Background: High doses of methotrexate (MTX) are often used in various chemotherapy protocols to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) in children, but its delayed elimination increases the occurrence of adverse events, such as bone marrow suppression. The aim of this study was to investigate the elimination of MTX at 24 and 48 hours. Methods: We retrospectively analyzed electronic medical records of ALL or NHL pediatric patients who received 5 g/m2 MTX infusion over 24 hours (between June, 2012 and July, 2018) at the Yonsei University Health System, Korea. The delayed elimination of MTX concentrations was assessed with 100 or 150 μM MTX at 24 hours, and 2 or 5 μM at 48 hours. Results: Among the 85 MTX cycles administered, 23 cycles were classified in delayed elimination group, and 62 cycles showed normal elimination. At 24 hours, the delayed elimination group with MTX concentration > 100 μM showed higher percentage than group with MTX concentration < 100 μM (45.8% vs. 19.7%, p = 0.015). However, no differences were observed at 150 μM MTX (p = 0.66). At 48 hours, the delayed elimination was higher than the normal elimination at both concentration baselines (p < 0.001 at 2 μM, p = 0.024 at 5 μM). Conclusions: MTX concentrations greater than 100 μM show high probability of delayed elimination at 24 hours. When MTX levels are above normal, leucovorin and hydration regimens should be continued to prevent delayed elimination.