G. A. Radzhabova, T. T. Valiev, Yu. E. Ryabukhina, M. I. Savelyeva, S. P. Abdullaev, O. D. Gurieva, P. A. Zeynalova
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引用次数: 0
摘要
背景。在治疗高级别侵袭性非霍奇金淋巴瘤和急性淋巴细胞白血病方面取得的一项重大进展是将大剂量(1000-5000 毫克/平方米)甲氨蝶呤纳入治疗方案。这种方法大大提高了长期存活率,但也存在毒性,需要支持性治疗。研究发现了预测毒性的因素,包括参与甲氨蝶呤代谢(MTHFR)或转运(SLCO1B1)的基因。对甲氨蝶呤代谢的分析发现了更多负责消除这种药物的基因,从而可以更有效地预防和治疗甲氨蝶呤相关毒性。研究在治疗小儿急性淋巴细胞白血病和非霍奇金淋巴瘤的过程中,参与甲氨蝶呤代谢和相关毒性的酶的基因多态性。对2001年至2024年期间Pubmed、Scopus、Web of Science、Frontiers和Google Scholar等专业医学数据库中的数据进行了分析。大剂量甲氨蝶呤相关毒性的主要预测因素是MTHFR、SLCO1B1和ARID5B的基因多态性。尽管文献中提供的数据相互矛盾,但在大剂量甲氨蝶呤治疗期间考虑检测多态性以及时采取支持性治疗并预防重大毒性是非常重要的。
Genetic polymorphisms as predictors of methotrexate toxicity: literature review
Background. A significant advancement in the treatment of high-grade aggressive non-Hodgkin’s lymphomas and acute lymphoblastic leukemia is the inclusion of high-dose (1000–5000 mg/m2) methotrexate in the treatment protocol. This approach has significantly increased the long-term survival rate, but it has been associated with toxicity, requiring supportive care. Factors that predict toxicity were identified, including genes involved in the metabolism (MTHFR) or transport (SLCO1B1) of methotrexate. The analysis of methotrexate metabolism has identified additional genes responsible for the elimination of this drug, allowing for more effective prevention and treatment of methotrexate-associated toxicity.Aim. To study the genetic polymorphisms of enzymes involved in the methotrexate metabolism and associated toxicity in the treatment of pediatric acute lymphoblastic leukemia and non-Hodgkin’s lymphomas.Materials and methods. Data were analyzed in specialized medical databases such as Pubmed, Scopus, Web of Science, Frontiers, and Google Scholar from 2001 to 2024.Results. The main predictors of high-dose methotrexate-associated toxicity are gene polymorphisms in MTHFR, SLCO1B1, ARID5B.Conclusion. Despite the contradictory data presented in the literature, it is important to consider the detection of polymorphisms during high-dose methotrexate treatment in order to administer timely supportive care and prevent significant toxicity.