Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma
Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma
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DOI：
10.1097/01.mph.0000198269.61948.90
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发表时间：
2006-02-01
影响因子：
1.2
通讯作者：
Kosaki, K
中科院分区：
文献类型：
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作者：
Shimasaki, N;Mori, T;Kosaki, K
作者研究了高剂量蛋氨酸诱导的毒性是否根据亚甲基四氢叶酸还原酶（MTHFR）或还原叶酸载体1（RFC 1）遗传多态性的存在而不同。作者研究了15名患有急性淋巴细胞白血病或淋巴细胞淋巴瘤的儿童，他们使用包括大剂量甲氨蝶呤（3.0 g/m2）的方案进行治疗，总共43个疗程。回顾性评价甲氨蝶呤诱导的毒性和血浆甲氨蝶呤浓度。血液学毒性是最常见的毒性，出现在87%的患者中。在一个子集的患者（47%），肝转氨酶水平升高显示出反复发展的趋势。甲氨蝶呤输注后48小时的高血浆甲氨蝶呤浓度与甲氨蝶呤诱导的毒性（粘膜炎除外）无显著相关性。广义估计方程分析显示，在高剂量甲氨蝶呤治疗期间呕吐在RFC 1 80 G> A多态性具有大量G等位基因的患者中更明显。对于不同的MTHFR 677 C> T或RFC 1 80 G> A多态性，未观察到其他毒性的发展或血浆甲氨蝶呤浓度的显著差异。这项研究表明，但并没有证明，RFC 1 80 G> A多态性可能有助于个体间的差异，对高剂量甲氨蝶呤的反应。
The authors investigated whether high-dose methotrexate-induced toxicity differed according to the presence of methylenetetrahydrofolate reductase (MTHFR) or reduced folate carrier 1 (RFC1) genetic polymorphism. The authors studied 15 children with acute lymphoblastic leukemia or lymphoblastic lymphoma who were treated using protocols that included high-dose methotrexate (3.0 g/m(2)), for an overall total of 43 courses. Methotrexate-induced toxicities and the plasma methotrexate concentrations were evaluated retrospectively. Hematologic toxicity was the most frequently observed toxicity, appearing in 87% of the patients. In a subset of patients (47%), elevation of liver transaminase levels showed a repeated tendency to develop. High plasma methotrexate concentrations at 48 hours after the methotrexate infusion were not significantly related to methotrexate-induced toxicities except for mucositis. A generalized estimating equation analysis revealed that vomiting during the high-dose methotrexate treatment was more pronounced in patients who had a larger number of G alleles at the RFC1 80G > A polymorphism. No significant differences in the development of other toxicities or in the plasma methotrexate concentrations were observed for the different MTHFR 677C > T or RFC1 80G > A polymorphisms. This study suggests but does not prove that the RFC1 80G > A polymorphism may contribute to interindividual variability in responses to high-dose methotrexate.