Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
J Chemother. 2020 Sep;32(5):251-259. doi: 10.1080/1120009X.2020.1764280. Epub 2020 May 20.
Whether plasma MTX concentrations and MTHFR C677T and A1298C polymorphisms could be used as a predictor of occurrence of MTX-related toxicities in Korean paediatric patients with acute lymphoblastic leukaemia (ALL) were assessed. HD-MTX related toxicities, MTHFR polymorphisms and MTX plasma concentrations following 337 HD-MTX cycles to 117 children with ALL on maintenance therapy were analyzed. A significantly higher frequency of hyperbilirubinemia ( = 0.0443) and renal toxicity ( = 0.0107) were associated with high MTX concentrations by Fisher's exact test. Moreover, high MTX concentrations at 24 h, 48, and 72 h were significantly associated with increased frequency of vomiting ( < 0.05) and hyperbilirubinemia ( < 0.05) by Mann-Whitney U test. There was a significantly higher frequency of mucositis in patients with the MTHFR 677 TT genotype ( = 0.0273) and a significantly higher frequency of MTX dose reduction in patients with the 677 TT genotype ( = 0.0217), compared to the CC/CT genotype. Independently, plasma MTX concentrations and MTHFR C677T genotype could be useful markers for tailoring MTX dosing and monitoring adverse effects in childhood ALL HD-MTX therapy in Korean patients.
评估了血浆 MTX 浓度和 MTHFR C677T 和 A1298C 多态性是否可用于预测韩国儿童急性淋巴细胞白血病（ALL）患者接受大剂量甲氨蝶呤（HD-MTX）治疗时发生 MTX 相关毒性的情况。对 117 例接受维持治疗的 ALL 患儿进行了 337 次 HD-MTX 周期的 HD-MTX 相关毒性、MTHFR 多态性和 MTX 血浆浓度分析。Fisher 确切检验显示，高 MTX 浓度与高胆红素血症（=0.0443）和肾毒性（=0.0107）的发生率显著相关。此外，24 小时、48 小时和 72 小时 MTX 浓度较高与呕吐（<0.05）和高胆红素血症（<0.05）的发生率增加显著相关，通过 Mann-Whitney U 检验。MTHFR 677 TT 基因型患者的黏膜炎发生率明显更高（=0.0273），677 TT 基因型患者的 MTX 剂量减少发生率明显更高（=0.0217），与 CC/CT 基因型相比。独立地，血浆 MTX 浓度和 MTHFR C677T 基因型可能是韩国儿童 ALL HD-MTX 治疗中调整 MTX 剂量和监测不良反应的有用标志物。
