儿童朗格汉斯细胞组织细胞增生症临床特征与BRAF V600E基因突变的相关性分析  

A retrospective analysis on Langerhans cell histiocytosis and the association between BRAF V600E mutation status and clinical features in children

作　　者：冯楚础 黎阳[1] 彭晓敏[1] 熊稀霖[1] 翁文骏[1] 邬萍萍 Feng Chuchu;Li Yang;Peng Xiaomin;Xiong Xilin;Weng Wenjun;Wu Pingping(Department of Pediatric Hematology/Oncology,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,China)

机构地区：[1]中山大学孙逸仙纪念医院儿科血液/肿瘤专科,广州510120

出　　处：《中华实用儿科临床杂志》2021年第11期848-852,共5页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的总结儿童朗格汉斯细胞组织细胞增生症(LCH)的临床特征,分析BRAF V600E基因突变与LCH的相关性。方法回顾性分析中山大学孙逸仙纪念医院儿科肿瘤专科2013年4月至2019年12月收治的60例LCH患儿的临床特征,其中有39例患儿完善BRAF V600E基因检测,分别采用实时定量聚合酶链反应(qRT-PCR)及高通量测序方法检测病灶活检组织及骨髓液/外周血BRAF V600E基因突变,分析BRAF V600E基因突变与LCH的相关性。结果1.临床特点:60例患儿年龄(4.08±0.45)岁;男43例,女17例;年龄≤2岁、危险器官(RO+)、中枢神经系统(CNS)危险部位受累患儿主要集中于多系统累及(MS)组(P<0.05)。2.初始诱导治疗疗效影响因素:60例患儿,评估治疗有效28例(41.7%),无效32例(53.3%);控制治疗方案分层因素的影响后,年龄≤2岁(OR=4.944,95%CI:1.601~15.275,P=0.005)、MS(OR=6.855,95%CI:2.077~22.622,P=0.002)是初始治疗疗效不佳的危险因素;对于JLSG-02治疗方案患儿,RO+是初始治疗疗效不佳的危险因素(OR=8.250,95%CI:1.617~42.090,P=0.005);而在CCHG-LCH-2019治疗方案患儿中,RO+对初始治疗疗效无影响。3.BRAF V600E基因突变情况:病灶活检组织的BRAF V600E基因阳性率为70.3%(26/39例),BRAF V600E基因突变阳性与初始治疗疗效、发病年龄、性别、MS、RO+等临床特征无相关性,但MS、CNS危险部位受累患儿BRAF V600E阳性率较同因素阴性者高,分别为76.0%(19例)比57.1%(8例)和74.1%(20例)比58.3%(7例);8例患儿完善骨髓液BRAF V600E基因检测,3例阳性,其中2例MS、1例多发骨侵犯;5例患儿完善外周血BRAF V600E基因检测,1例阳性,为MS伴肝脾器官受累。结论年龄≤2岁、MS、RO+的LCH患儿初始治疗反应差,临床上需采取积极的治疗方案;病灶BRAF V600E基因突变发生率高,提示LCH是一种克隆性疾病;LCH患儿中BRAF V600E基因突变与MS、CNS危险部位受累存在较大的相关性,部分患儿存在骨髓/外周血BRAF V600E突变阳性,提示该�Objective To investigate the clinical features of patients with Langerhans cell histiocytosis(LCH),and analyze the association between BRAF V600E mutation status and clinical features.Methods A retrospective analysis was carried out for the clinical data of 60 patients with LCH at the Department of Pediatric Oncology,Sun Yat-sen Memorial Hospital between April 2013 and December 2019.Among them,39 patients undertook BRAF V600E mutation testing,which in paraffin-embedded tissue samples were detected by quantitative real-time PCR(qRT-PCR),and in peripheral blood and/or bone marrow were tested by high-throughput sequencing,for analyzing the correlation between BRAF V600E mutation and clinical characteristics of LCH.Results(1)Clinical characteristics:the age of 60 LCH patients was(4.08±0.45)years,with 43 male cases and 17 female cases.Patients at young age(≤2 years)and with risk organ(RO+)and central nervous system(CNS)risk lesions involvement were concentrated in the multisystem involvement(MS)group(P<0.05).(2)Therapeutic response after induction therapy:the response to induction therapy was achieved in 28 of 60 treated patients(41.7%)and 32(53.3%)did not.After excluding stratification factors of treatment regimen,MS(OR=6.855,95%CI:2.077-22.622,P=0.002)and the age≤2 years(OR=4.944;95%CI:1.601-15.275;P=0.005)were risk factors in poor chemotherapy response.RO+(OR=8.250,95%CI:1.617-42.090,P=0.005)was a significant risk factor for a poor chemotherapy response in JLSG-02 treatment group.Differently,RO+had no dramatic effect on chemotherapy response in CCHG-LCH-2019 treatment group.(3)BRAF V600E mutation:39 patients were determined BRAF V600E status,with the positive rate of BRAF V600E mutation in paraffin-embedded tissue samples reaching 70.3%(26 cases).BRAF V600E mutation was not associated with early treatment response,age,sex,MS and RO+(P>0.05).However,the positive rate of BRAF V600E in children with MS and CNS risk lesions was higher than the controls,with 76.0%(19 cases)vs.57.1%(8 cases)and 74.1%(20 cases)vs.58.

关 键 词：朗格汉斯细胞组织细胞增生症 BRAF V600E基因 危险因素 儿童 

分 类 号：R725.9[医药卫生—儿科]