摘要
目的:分析BRAF V600E抑制剂(包括维罗非尼和达拉非尼)在小儿朗格罕斯组织细胞增生症(LCH)临床治疗中的疗效和安全性。方法:分析我院小儿LCH病例,并检索2011—2018年国内外期刊应用BRAF V600E抑制剂治疗小儿LCH的病例报道,对患者基本资料、BRAF V600E抑制剂的疗效和安全性等数据进行统计分析。结果:我院患儿诊断为多系统高危险度LCH,予改良LCH-Ⅲ方案治疗效果不佳;在检测到BRAF V600E(1799T> A)基因突变后,予达拉非尼治疗,病情得以控制,BRAF V600E基因突变转阴,患儿耐受性较好。对检索到的病例进行分析,5例应用BRAF V600E抑制剂治疗的小儿LCH个案病例中,3例患儿应用达拉非尼治疗6～12周后获得分子生物学完全缓解,且主要临床表现得到完全缓解,并未观察到达拉非尼相关的不良反应发生。2例患儿应用维罗非尼治疗,其中1例共治疗18个月,另1例治疗5个月,均获得分子生物学完全缓解,且主要临床表现得到完全缓解,但1例出现高血压、眉毛稀疏和皮肤干燥等不良反应,另1例出现皮疹。结论:对于BRAF V600E突变的多系统性LCH患儿,可尝试应用达拉非尼或维罗非尼治疗,但应加强监护。
Objective:To analyze the efficacy and safety of BRAF V600 E inhibitors(including vemurafenib and dabrafenib)in the treatment of pediatric Langerhans cell histiocytosis(LCH).Methods:The case of pediatric LCH in our hospital were analyzed and pediatric LCH cases treated with BRAF V600 E inhibitors from 2011 to 2018 were searched.The basic data of these cases and the data of the efficacy and safety of BRAF V600 E inhibitors were analyzed.Results:For one case in our hospital,the child was diagnosed as multi-system high-risk LCH,and was treated with modified LCH-Ⅲregimen,but the regimen was ineffective.After detecting the mutation of BRAF V600 E(1799 T>A),he was treated with dabrafenib.In the end,the disease was controlled,and BRAF V600 E mutation turned negative.Luckily,the child was able to tolerate the therapy with dabrafenib.Totally 5 cases of pediatric LCH treated with BRAF V600 E inhibitors were analyzed.3 cases had complete molecular response after 6 to 12 weeks of treatment with dabrafenib and the main clinical manifestations were complete remission without occurrence of adverse reactions associated with dabrafenib.2 cases were treated with vemurafenib.Among them,one was treated for 18 months and the other one was treated for 5 months.All of them achieved complete molecularresponse and the main clinical manifestations were completely relieved.However,1 patient developed hypertension,eyebrows sparse and dry skin,and the other case had rash.Conclusion:For multi-system high-risk pediatric LCH with BRAF V600 E mutation,treatment with dabrafenib or vemurafenib may be attempted,but should strengthen to monitor its toxicity and safety.
作者
闫美玲
张萌
黄琳
贾月萍
张弋
冯婉玉
YAN Mei-ling;ZHANG Meng;HUANG Lin;JIA Yue-ping;ZHANG Yi;FENG Wan-yu(Department of Pharmacy,Tianjin First Center Hospital,Tianjin 300192,China;Department of Pharmacy,Peking University People's Hospital,Beijing 100044,China;Pediatric Department,Peking University People's Hospital,Beijing 100044,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2019年第7期886-890,共5页
Chinese Journal of New Drugs
基金
天津市卫计委科技基金资助项目(2015KY09)
