应用西罗莫司安全有效治疗并发血细胞减少的儿童自身免疫性淋巴细胞增生综合征——单中心、回顾性队列研究  

Effective and safe treatment of sirolimus in the childhood autoimmune lymphoproliferative syndrome with hemocytopenia-a single center,retrospective cohort study

作　　者：谷昊[1] 陈振萍[1] 马洁[1] 马静瑶[1] 傅玲玲[1] 张蕊[1] 王天有[1] 吴润晖[1] GU Han;CHEN Zhenping;MA Jie;MA Jingyao;FU Lingling;ZHANG Rui;WANG Tianyou;WU Runhui(Hematology Center,Beijing Key Laboratory of Pediatric Hematology Oncology,National Key Discipline of Pediatrics,Capital Medical University,Key Laboratory of Major Diseases in Children,Ministry of Education,Beijing Childrens Hospital,Capital Medical University,National Center for Childrens Health,Bejing,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

出　　处：《临床血液学杂志》2021年第7期477-482,共6页Journal of Clinical Hematology

基　　金：国家自然科学基金课题(No:81970111);国家科技重大专项资助(No:2017ZX09304029001);北京市自然科学基金课题(No:7192064);北京市医院管理中心儿科学科协同发展中心“儿科专项”(No:XTZD20180205)。

摘　　要：目的:自身免疫性淋巴细胞增生综合征(ALPS)是一种常在幼年发病、并发免疫性血细胞减少而需要药物控制的遗传性免疫缺陷病。而糖皮质激素作为传统治疗药物将影响处于生长发育的患儿。西罗莫司通过精准抑制mTOR通路、诱导T细胞凋亡而成为治疗的新选择,但尚缺乏其安全性和有效性数据。本文旨在通过总结我中心伴发免疫性血细胞减少的ALPS患儿西罗莫司用药数据,为该药在ALPS患儿的应用提供数据。方法:单中心、回顾性队列研究,收集自2016年至今在我中心确诊并应用西罗莫司治疗超过1年的12例并发免疫性血细胞减少的ALPS患儿,对治疗的有效性和安全性进行评价。结果:12例患儿中位年龄3.5(110)岁,中位病程10个月(1个月3年)。12例(100%)均存在免疫性血小板减少:其中7例(58.33%)累及全血细胞,4例(33.33%)累及两系血细胞,1例(8.33%)仅累及免疫性血小板减少。12例(100%)存在中度以上脾肿大(3例达Ⅲ度),11例(91.67%)伴淋巴结肿大。疗效方面:(1)疗程3个月时,12例(100%)血细胞减少缓解,9例(75.00%)达完全缓解;10例(83.33%)淋巴组织增殖缓解,3例(25.00%)达完全缓解。(2)疗程12个月时,12例(100%)血细胞减少缓解,11例(91.67%)达完全缓解;12例(100%)淋巴组织增殖缓解,8例(66.67%)达完全缓解。(3)患儿血细胞减少先于淋巴增殖缓解:血细胞减少中位达完全缓解时间3周(150周)。(4)缓解相关因素:ALPS-FAS及ALPS-FASLG突变患儿于3个月评估点均达血常规及淋巴增殖缓解,时间早于其余ALPS患儿。应用3个月、6个月达完全缓解者病初双阴性T细胞比例明显增高。安全性方面:1例患儿服药期间谷丙转氨酶升高,2例口腔溃疡,尚无患儿因服药继发感染。结论:西罗莫司治疗儿童期并发血细胞减少的ALPS起效快、缓解率高:疗程1年时血细胞减少及淋巴增殖总有效率高达100%(血细胞减少完全缓解率91.67%、淋巴增殖完全缓解Objective: Autoimmune lymphoproliferative syndrome(ALPS) usually presents in childhood with fever, nonmalignant splenomegaly and lymphadenopathy along with cytopenia. Glucocorticoids, as a traditional therapeutic application of ALPS, will affect the growth of children. Sirolimus has become a new treatment option which accurately inhibit the mTOR pathway and induce T cell apoptosis, but its safety and effectiveness data in pediatrics still need to be investigated. This article aims to provide safety and effectiveness data for the application of sirolimus in the childhood ALPS with hemocytopenia in our center. Methods: This study was a single-center, retrospective cohort study, collected from 2016 to present, 12 pediatric ALPS with immune cytopenia diagnosed and treated with sirolimus for more than 1 year. The data of effectiveness and safety was evaluated. Results: The median age of the 12 children was 3.5(1-10) years old, and the median course of disease was 10 months(1 month to 3 years). Twelve cases(100%) all had immune thrombocytopenia: 7 cases(58.33%) had pancytopenia, 4 cases(33.33%) involved two lines hemocytopenia, and 1 case(8.33%) only had immune thrombocytopenia. Twelve cases(100%) had moderate or higher splenomegaly(3 cases reached degree Ⅲ), and 11 cases(91.67%) had lymphadenopathy. Efficacy:(1)After 3 months of treatment, 12 cases(100%) achieved remission of cytopenia, and 9 cases(75.00%) achieved complete remission. Ten cases(83.33%) achieved remission of lymphoid tissue proliferation, and 3 cases(25.00%) achieved complete remission.(2)At 12 months of treatment, 12 cases(100%) achieved remission of cytopenia, and 11 cases(91.67%) achieved complete remission. Twelve cases(100%) achieved remission of lymphoid tissue proliferation, and 8 cases(66.67%) achieved complete remission.(3)The median time to complete remission of hemacytopenia was 3 weeks(1-50 weeks), which was shorter than that of lymphatic proliferation.(4)Relation factors: All the children with ALPS-FAS and ALPS-FASLG mutations achieved h

关 键 词：自身免疫性淋巴细胞增生综合征 西罗莫司 儿童 

分 类 号：R557.4[医药卫生—血液循环系统疾病]