芦可替尼联合脂质体阿霉素、依托泊苷、甲泼尼龙和(或)培门冬酶对儿童复发/难治性噬血细胞综合征的疗效分析  

Ruxolitinib combined with liposomal doxorubicin,etoposide,methylprednisolone+/-PEG‑asparaginase in treatment of relapsed/refractory pediatric hemophagocytic lymphohistiocytosis

作　　者：魏昂 马宏浩[1] 张利平 廉红云[1] 杜俊烨 王冬[1] 崔蕾[2] 欧雯欣 赵云泽 赵晓曦[2] 张莉[1] 李志刚[2] 王天有[1] 张蕊[1] Wei Ang;Ma Honghao;Zhang Liping;Lian Hongyun;Du Junye;Wang Dong;Cui Lei;Ou Wenxin;Zhao Yunze;Zhao Xiaoxi;Zhang Li;Li Zhigang;Wang Tianyou;Zhang Rui(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;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]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市儿科研究所血液疾病研究室,北京100045

出　　处：《中华医学杂志》2022年第28期2167-2172,共6页National Medical Journal of China

基　　金：国家科技重大专项(2017ZX09304029001);北京市自然科学基金(7214226);北京市医院管理中心儿科学科协同发展中心专项(XTZD20180202)。

摘　　要：目的分析芦可替尼联合脂质体阿霉素、依托泊苷、甲泼尼龙和(或)培门冬酰胺酶(RU‑DEP+/-L)对儿童复发/难治性(R/R)噬血细胞综合征[噬血细胞性淋巴组织细胞增多症(HLH)]的疗效以及安全性。方法回顾性分析2018年1月至2019年12月期间于首都医科大学附属北京儿童医院血液病中心应用RU‑DEP+/-L治疗的R/R HLH患儿。结果共纳入16例患儿,男13例、女3例,诊断时年龄[M(Q_(1),Q_(3))]为1(1,2)岁。13例患儿诊断为EB病毒(EBV)‑HLH,2例为EBV诱发的原发性HLH,1例为不明原因HLH,其中3例EBV‑HLH同时合并巨细胞病毒(CMV)感染。一线治疗后,11例无反应,5例达到完全反应后再次复发。9例患儿采用了RU‑L‑DEP方案,7例患儿采用了RU‑DEP方案。RU‑DEP+/-L治疗总体反应率为10/16,完全反应率3/16,血浆EBV‑DNA阴转率为7/15。随访时间35.1(2.4,40.7)个月,9/16患儿存活。RU‑DEP+/-L治疗后获得反应衔接造血干细胞移植(HSCT)3年总生存率高于挽救治疗后无反应、未行HSCT患儿(P=0.048)。16例患儿中有9例出现不同程度的骨髓抑制,13例合并感染。结论RU‑DEP+/-L可作为挽救治疗药物用于儿童R/R HLH的二线方案,可有效控制部分患儿HLH活动,为后续HSCT提供机会。不良反应主要是骨髓抑制及并发感染,患儿耐受可。Objective To investigate the efficacy and safety of ruxolitinib,liposomal doxorubicin,etoposide,methylprednisolone+/-PEG‑asparaginase(RU‑DEP+/-L)in the treatment of relapsed/refractory(R/R)pediatric hemophagocytic lymphohistiocytosis(HLH).Methods The clinical data of R/R pediatric HLH,who accepted the RU‑DEP+/-L regimen at Beijing Children′s Hospital from January 2018 to December 2019 was retrospectively analyzed.Results A total of 16 patients were included in this study,including 13 males and 3 females,aged[M(Q_(1),Q_(3))]1(1,2)years at diagnosis.Thirteen patients were diagnosed with Epstein‑Barr virus(EBV)‑HLH,2 with EBV‑induced primary HLH,and 1 with unclear etiology,among which 3 patients were co‑infected with CMV.After the first‑line treatment,11 patients had no response,and 5 patients relapsed after complete response.Nine patients received the RU‑L‑DEP regimen,and 7 patients received the RU‑DEP regimen.The overall response rate and complete response of RU‑DEP+/-L treatment were 10/16 and 3/16,respectively.The negative conversion rate of plasma EBV‑DNA was 7/15.The median follow‑up time was 35.1(2.4,40.7)months,and 9/16 patients were survival.The 3‑year overall survival rate after RU‑DEP+/-L treatment in response and accepted hematopoietic stem cell transplantation(HSCT)was higher than that without response and did not receive HSCT(P=0.048).Among the 16 patients,9 had varying degrees of myelosuppression,and 13 had an infection.Conclusions RU‑DEP+/-L can be used as a salvage treatment in R/R pediatric HLH,which can provide a bridge to HSCT and play an important role in the control of HLH.The main adverse reactions are myelosuppression and infection,which can be tolerated.

关 键 词：噬血细胞综合征 儿童 复发 难治 预后 随访研究 

分 类 号：R725[医药卫生—儿科]