{"title":"l -天冬酰胺酶治疗儿童急性淋巴细胞白血病的疗效和毒性","authors":"D. S. Smirnova, T. T. Valiev","doi":"10.24287/1726-1708-2023-22-3-192-198","DOIUrl":null,"url":null,"abstract":"L-asparaginase, an enzyme used as an anticancer drug, was one of the first drugs included in the treatment protocols for acute lymphoblastic leukemia. It has become widely used when an important metabolic feature of leukemia cells – their high demand for asparagine to maintain viability – was discovered. Three L-asparaginase preparations are currently used in clinical practice: native E. coli asparaginase, pegylated E. coli asparaginase (PEG-asparaginase), and native E. chrysanthemi-derived asparaginase, which have different half-lives, immunogenic profiles, and the spectrum and frequency of toxic effects. One of the main factors limiting the use of L-asparaginase is its high immunogenicity which can cause acute allergic reactions and the phenomenon of silent inactivation. The development of the immune response leads to an accelerated asparaginase clearance and a shortening of its half-life. To monitor the effectiveness of therapy with L-asparaginase, therapeutic drug monitoring of serum asparaginase activity can be used. When choosing management strategies for patients experiencing acute hypersensitivity reactions to L-asparaginase, the following factors should be taken into consideration: the severity of reaction, the number of previous exposures to L-asparaginase and serum asparaginase activity. The use of PEG-asparaginase is the best first-line treatment strategy for children acute lymphoblastic leukemia, its advantages include a significant reduction in the risk of developing acute allergic reactions, higher therapeutic efficacy and, as a result, improved treatment outcomes.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"2014 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The efficacy and toxicity of L-asparaginase in the treatment of acute lymphoblastic leukemia in children\",\"authors\":\"D. S. Smirnova, T. T. Valiev\",\"doi\":\"10.24287/1726-1708-2023-22-3-192-198\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"L-asparaginase, an enzyme used as an anticancer drug, was one of the first drugs included in the treatment protocols for acute lymphoblastic leukemia. It has become widely used when an important metabolic feature of leukemia cells – their high demand for asparagine to maintain viability – was discovered. Three L-asparaginase preparations are currently used in clinical practice: native E. coli asparaginase, pegylated E. coli asparaginase (PEG-asparaginase), and native E. chrysanthemi-derived asparaginase, which have different half-lives, immunogenic profiles, and the spectrum and frequency of toxic effects. One of the main factors limiting the use of L-asparaginase is its high immunogenicity which can cause acute allergic reactions and the phenomenon of silent inactivation. The development of the immune response leads to an accelerated asparaginase clearance and a shortening of its half-life. To monitor the effectiveness of therapy with L-asparaginase, therapeutic drug monitoring of serum asparaginase activity can be used. When choosing management strategies for patients experiencing acute hypersensitivity reactions to L-asparaginase, the following factors should be taken into consideration: the severity of reaction, the number of previous exposures to L-asparaginase and serum asparaginase activity. The use of PEG-asparaginase is the best first-line treatment strategy for children acute lymphoblastic leukemia, its advantages include a significant reduction in the risk of developing acute allergic reactions, higher therapeutic efficacy and, as a result, improved treatment outcomes.\",\"PeriodicalId\":38370,\"journal\":{\"name\":\"Pediatric Hematology/Oncology and Immunopathology\",\"volume\":\"2014 1\",\"pages\":\"0\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Hematology/Oncology and Immunopathology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.24287/1726-1708-2023-22-3-192-198\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Hematology/Oncology and Immunopathology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.24287/1726-1708-2023-22-3-192-198","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
摘要
l -天冬酰胺酶是一种用作抗癌药物的酶,是急性淋巴细胞白血病治疗方案中首批纳入的药物之一。当白血病细胞的一个重要代谢特征——它们对天冬酰胺的高需求来维持生存能力——被发现后,它被广泛应用。目前临床应用的l -天冬酰胺酶制剂有三种:天然大肠杆菌天冬酰胺酶、聚乙二醇化大肠杆菌天冬酰胺酶(peg -天冬酰胺酶)和天然菊花源天冬酰胺酶,它们具有不同的半衰期、免疫原性特征以及毒性作用的谱和频率。限制l -天冬酰胺酶使用的主要因素之一是其免疫原性高,可引起急性过敏反应和沉默失活现象。免疫反应的发展导致天冬酰胺酶的加速清除和缩短其半衰期。为了监测l -天冬酰胺酶治疗的有效性,可以使用治疗药物监测血清天冬酰胺酶活性。在对l -天冬酰胺酶急性超敏反应患者选择治疗策略时,应考虑以下因素:反应的严重程度、既往l -天冬酰胺酶暴露次数和血清天冬酰胺酶活性。使用peg -天冬酰胺酶是儿童急性淋巴细胞白血病的最佳一线治疗策略,其优点包括显著降低急性过敏反应的发生风险,提高治疗效果,从而改善治疗效果。
The efficacy and toxicity of L-asparaginase in the treatment of acute lymphoblastic leukemia in children
L-asparaginase, an enzyme used as an anticancer drug, was one of the first drugs included in the treatment protocols for acute lymphoblastic leukemia. It has become widely used when an important metabolic feature of leukemia cells – their high demand for asparagine to maintain viability – was discovered. Three L-asparaginase preparations are currently used in clinical practice: native E. coli asparaginase, pegylated E. coli asparaginase (PEG-asparaginase), and native E. chrysanthemi-derived asparaginase, which have different half-lives, immunogenic profiles, and the spectrum and frequency of toxic effects. One of the main factors limiting the use of L-asparaginase is its high immunogenicity which can cause acute allergic reactions and the phenomenon of silent inactivation. The development of the immune response leads to an accelerated asparaginase clearance and a shortening of its half-life. To monitor the effectiveness of therapy with L-asparaginase, therapeutic drug monitoring of serum asparaginase activity can be used. When choosing management strategies for patients experiencing acute hypersensitivity reactions to L-asparaginase, the following factors should be taken into consideration: the severity of reaction, the number of previous exposures to L-asparaginase and serum asparaginase activity. The use of PEG-asparaginase is the best first-line treatment strategy for children acute lymphoblastic leukemia, its advantages include a significant reduction in the risk of developing acute allergic reactions, higher therapeutic efficacy and, as a result, improved treatment outcomes.