克拉屈滨联合阿糖胞苷治疗儿童难治复发性朗格罕细胞组织细胞增生症疗效分析  

Cladribine and Cytarabine combinations in treatment of patients with refractory and recurrent Langerhans cell histiocytic

作　　者：马宏浩[1] 魏昂 张利平 廉红云[1] 崔蕾 杨颖[1] 王冬[1] 李理 杜俊烨 张莉[1] 王婵娟 赵云泽 赵晓曦 李志刚 张蕊[1] 王天有[1] MA Honghao;WEI Ang;ZHANG Liping;LIAN Hongyun;CUI Lei;YANG Ying;WANG Dong;LI Li;DU Junye;ZHANG Li;WANG Chanjuan;ZHAO Yunze;ZHAO Xiaoxi;LI Zhigang;ZHANG Rui;WANG Tianyou(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;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,100045 Beijing,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,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,北京100045 [2]北京市儿科研究所血液疾病研究室

出　　处：《中国小儿血液与肿瘤杂志》2024年第3期159-165,共7页Journal of China Pediatric Blood and Cancer

基　　金：国家自然科学基金项目(编号:82070202);首都卫生发展科研专项项目(编号:首发2020-2-2093、2020-2-1141);北京市医院管理中心儿科学科协同发展中心专项项目(编号:XTZD20180201);国家科技重大专项项目(编号:2017ZX09304029004);北京市卫生健康委员会改革与发展经费项目。

摘　　要：目的分析克拉屈滨(2-CDA)联合阿糖胞苷(Ara-c)治疗儿童难治复发性朗格罕细胞组织细胞增生症(LCH)的疗效以及毒副作用。方法回顾性分析2018年1月—2022年10月期间于首都医科大学附属北京儿童医院血液病中心确诊的难治复发性LCH患儿,均采用2-CDA联合Ara-C方案化疗。结果患儿共94例,男64例,女30例,中位年龄5.38(0.45-13.61)岁。多系统受累组共78例(82.9%),危险器官受累组共32例(34.0%)。初诊时61例检测了血浆BRAF^(V600E),阳性率49.18%,47例检测了组织BRAF^(V600E),阳性率78.72%。总体治疗反应率为85.1%,44.4%尿崩症好转,3年EFS为(76.7±3.4)%,2年累积进展或复发率为20.2%。骨髓抑制及消化道反应为最常见的不良反应(100%),无化疗相关死亡。发病年龄小(中位年龄<1.63岁)、加用二线药物时年龄偏小(中位年龄<1.82岁)、多系统受累、危险器官受累及BRAF^(V600E)突变的患儿更易出现复发和疾病进展(P=0.016,0.001,0.043和<0.001)。结论2-CDA联合Ara-C可作为难治复发性LCH的挽救二线方案,对LCH垂体受累改善显著。副作用主要是骨髓抑制及胃肠道反应,总体耐受程度好,安全性高,无化疗相关死亡。但远期复发率及缓解率尚需随访观察。Objective To investigate the efficacy and safety of Cladribine(2-CDA)combined with Cytarabine(Ara-C)as a salvage therapy for pediatric refractory/recurrent Langerhans cell histiocytosis(LCH).Methods A retrospective analysis was performed in children with R/R LCH,who accepted 2-CDA plus Ara-C treatment at hematology center,Beijing Children′s Hospital,from January 2018 to October 2022.Results A total of 94 patients were enrolled in this study,including 64 boys and 30 girls,with a median age of 5.38(0.45-13.61)years at diagnosis.There were 78 and 32 patients with multisystem,risk-organ involvement respectively.At diagnosis,circulating cell-free BRAF^(V600E)(cfBRAF^(V600E))was positive in 30 of 61 patients(49.18%).Gene mutations in biopsy tissue was detected positive in 37 of 47 patients(78.72%).The overall response rate was 85.1%.The median follow-up time was 4.60(1.71-7.08)years.The 3-year event free survival rate was 76.7%±3.4%and the 2-year cumulative rate of progression or reactivation was 20.2%.In 30 patients with pituitary involvement,90%of the pituitary MRI abnormal signals recovered,44.4%of the diabetes insipidus symptoms improved after second-line treatment.All the 94 patients had myelosuppression and gastrointestinal reactions during chemotherapy,which were mild to moderate.Multivariate Logistic regression analysis showed that risk organ involvement,was independently correlated with reactivation or disease progression after second-line treatment(P=0.027,OR=3.138,95%CI=1.141-8.633).The factors with poor prognosis was median age of onset less than 1.63 years,a younger age with the addition of second-line drugs(less than 1.82 years),multisystem involvement and risk organ involvementand BRAF^(V600E)mutation.Conclusions 2-CDA plus Ara-C treatment can be used as a salvage therapy with high efficiency and low reactivation rate in paediatric R/R LCH,and had a certain effect on pituitary involvement.The main side effects were mild to moderate myelosuppression and gastrointestinal reactions.The long-term reactiva

关 键 词：朗格罕细胞组织细胞增生症 难治 复发 克拉屈滨 阿糖胞苷 

分 类 号：R725.5[医药卫生—儿科]