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Influence of plasma methotrexate level and MTHFR genotype in Korean paediatric patients with acute lymphoblastic leukaemia.
Journal of Chemotherapy ( IF 1.9 ) Pub Date : 2020-05-20 , DOI: 10.1080/1120009x.2020.1764280
Hyojin Chae 1, 2 , Myungshin Kim 1, 2 , Sun Hee Choi 3 , Seong-Koo Kim 3 , Jae-Wook Lee 3 , Nack-Gyun Chung 3 , Bin Cho 3 , Yonggoo Kim 1, 2
Affiliation  

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 (P = 0.0443) and renal toxicity (P = 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 (P < 0.05) and hyperbilirubinemia (P < 0.05) by Mann-Whitney U test. There was a significantly higher frequency of mucositis in patients with the MTHFR 677 TT genotype (P = 0.0273) and a significantly higher frequency of MTX dose reduction in patients with the 677 TT genotype (P = 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.



中文翻译:

血浆甲氨蝶呤水平和MTHFR基因型对韩国小儿急性淋巴细胞白血病的影响。

评估了韩国小儿急性淋巴细胞白血病(ALL)患者血浆MTX浓度以及MTHFR C677T和A1298C多态性是否可作为MTX相关毒性发生的预测指标。分析了对117例ALL维持治疗的儿童进行337个HD-MTX循环后的HD-MTX相关毒性,MTHFR多态性和MTX血浆浓度。 通过Fisher精确检验,高胆红素血症(P  = 0.0443)和肾毒性(P = 0.0107)的发生频率显着高于高MTX浓度。此外,在24、48和72小时的高MTX浓度与呕吐频率(P  <0.05)和高胆红素血症(P <0.05)通过Mann-Whitney U检验。 与CC / CT基因型相比,MTHFR 677 TT基因型患者的粘膜炎发生率显着更高(P  = 0.0273),而677 TT基因型患者的MTX降低剂量的频率显着更高(P = 0.0217)。 。独立地,血浆MTX浓度和MTHFR C677T基因型可能是用于调整MTX剂量和监测韩国患者童年ALL HD-MTX治疗不良反应的有用标志物。

更新日期:2020-05-20
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