达拉菲尼一线治疗婴幼儿多系统受累朗格罕细胞组织细胞增生症的疗效分析  

Efficacy of Dabrafenib as first-line therapy in infants with multisystem Langerhans cell histiocytosis

作　　者：王冬[1] 张利平 马宏浩[1] 赵云泽 廉红云[1] 崔蕾[2] 李志刚[2] 王天有[1] 张蕊[1] WANG Dong;ZHANG Liping;MA Honghao;ZHAO Yunze;LIAN Hongyun;CUI Lei;LI Zhigang;WANG Tianyou;ZHANG Rui(Hematology Center,Beijing Key Laboratory of Pediatric Hematology OncologyBeijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China;Hematologic Disease Laboratory,Beijing Pediatric Research Institute,Hematology Center,Beijing Key Laboratory of Pediatric Hematology Oncology,National Key Discipline of Pediatrics(Capital Medical University),Key Laboratory of Major Disease in Children,Ministry of Education,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China)

机构地区：[1]国家儿童医学中心,首都医科大学附属北京儿童医院血液病中心,北京100045 [2]国家儿童医学中心,首都医科大学儿童血液病与肿瘤分子分型北京市重点实验室,儿科学国家重点学科,儿科重大疾病研究教育部重点实验室,北京市儿科研究所血液疾病研究室,北京100045

出　　处：《中国小儿血液与肿瘤杂志》2024年第4期256-260,共5页Journal of China Pediatric Blood and Cancer

基　　金：国家自然科学基金项目(编号:82070202,82141119);北京市自然科学基金项目(编号:7232058,7242053);首都卫生发展科研专项项目(编号:首发2020-2-2093,2022-2-1141)。

摘　　要：目的探讨达拉菲尼作为一线用药治疗婴幼儿多系统受累BRAF^(V600E)基因突变阳性朗格罕细胞组织细胞增生症(LCH)的临床疗效。方法回顾性分析2020年1月-2022年12月北京儿童医院确诊的11例多系统受累BRAF^(V600E)基因突变阳性LCH患儿的临床资料,分析达拉菲尼的有效率、不良反应及复发率。结果11例LCH患儿中,男6例,女5例,诊断中位年龄10.5(2.0-20.8)个月,达拉菲尼治疗中位时间23(14-36)个月,治疗有效率100%,危险器官受累均完全恢复,3/4例患儿垂体受累恢复。中位随访时间38.2(14-51.8)个月,除1例失访外,另10例患儿均存活。6例停药患儿中4例复发(2例再次应用达拉菲尼仍有效),3年无事件生存率71.4%(95%CI:35.9-91.8)。用药期间4例患儿出现皮疹,1例出现心肌损害,对症治疗后均好转。结论达拉菲尼作为BRAF^(V600E)阳性的多系统受累LCH婴幼儿一线治疗有效率高、副作用小,但停药后复发率高,为实现长期缓解,需要进一步探索延长达拉菲尼疗程或桥接化疗等治疗手段。Objective To explore the clinical efficacy and safety of dabrafenib as first-line therapy in multisystem infants LCH with BRAF^(V600E)-mutation.Methods The clinical data of 11 infants with multisystem LCH with BRAF^(V600E)-mutation in Beijing Children′s Hospital from January 2020 to December 2022 was retrospectively analyzed,including the effective rate,adverse reactions and recurrence rate.Results Six males and 5 females were included in this study.The median age of diagnosis was 10.5 months(range,2.0-20.8months).The median time on dabrafenib was 23 months(range,14-36 months).The response rate was 100%.After treatment,the involvements of risk organs were completely recovered,3/4 children with pituitary involvement recovered.The median follow-up time was 38.2 months(range,14-51.8 months).All the other 10 patients were alive except for one child who was lost to follow-up.Among the 6 children who finished treatment completely,four cases relapsed.The 3-year event-free survival rate was 71.4%(95%confidence interval:35.9-91.8).During the treatment of dabrafenib,skin rash occurred in 4 cases and myocardial damage occurred in one case,all symptoms were improved after symptomatic treatment.Conclusions Multisystem infant LCH with BRAF^(V600E)-mutation had a high response rate when treated with frontline dabrafenib,and the drug-related side effects were tolerable.However,the recurrence rate was high.To achieve long-term remission,prolonged course of dabrafenib or subsequent chemotherapy need to be further explored.

关 键 词：婴幼儿 朗格罕细胞组织细胞增生症 多系统受累 达拉菲尼 

分 类 号：R725[医药卫生—儿科]