原发性免疫缺陷病患儿脐带血干细胞移植后巨细胞病毒感染危险因素及预后分析  

Analysis of risk factors and prognosis of cytomegalovirus infection post umbilical cord blood stem cell transplantation in children with primary immunodeficiency diseases

作　　者：韦忠玲 钱晓文 王苹 江文晋 王宏胜 沈晨 王文婕[2] 侯佳[2] 王玉环 黄瑛 王晓川[2] 翟晓文 Wei Zhongling;Qian Xiaowen;Wang Ping;Jiang Wenjin;Wang Hongsheng;Shen Chen;Wang Wenjie;Hou Jia;Wang Yuhuan;Huang Ying;Wang Xiaochuan;Zhai Xiaowen(Department of Hematology,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China;Department of Immunology,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China;Department of Gastroenterology,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China)

机构地区：[1]国家儿童医学中心,复旦大学附属儿科医院血液科,上海201102 [2]国家儿童医学中心,复旦大学附属儿科医院免疫科,上海201102 [3]国家儿童医学中心,复旦大学附属儿科医院消化科,上海201102

出　　处：《中华儿科杂志》2022年第10期1019-1025,共7页Chinese Journal of Pediatrics

基　　金：上海市科委重大项目(21Y31900302)。

摘　　要：目的探讨原发性免疫缺陷病(PID)患儿脐带血干细胞移植(UCBT)后发生巨细胞病毒(CMV)感染的危险因素及其对预后的影响。方法回顾性研究。收集2015年1月至2020年6月在复旦大学附属儿科医院接受UCBT的143例PID患儿的临床资料。UCBT后100 d内患儿每周进行1~2次血浆CMV-DNA检测, 根据结果分为CMV感染组与未感染组, 分析UCBT后100 d内CMV感染的发生率及危险因素。比较移植1个月后CMV感染患儿与未感染患儿在移植后1个月时的外周血中淋巴细胞亚群绝对计数、比例及免疫球蛋白水平的差异。组间比较采用非参数秩和检验或χ^(2)检验。采用Kaplan-Meier生存分析法比较CMV感染对预后的影响。结果 143例患儿中男113例、女30例, 移植时年龄为14(8, 27)月龄。原发病以慢性肉芽肿病(49例)、极早发型炎症性肠病(43例)及重症联合免疫缺陷病(29例)为主。CMV感染率为21.7%(31/143), 感染的时间为移植后44(31, 49)d。复发性CMV感染率为4.2%(6/143), 复发性CMV感染与非复发性CMV感染组间首次CMV-DNA的拷贝及治疗过程中的CMV-DNA拷贝峰值间差异均无统计学意义[32.8(18.3, 63.1)×10^(6)比22.5(13.2, 31.9)×10^(6)拷贝/L, Z=-0.95, P=0.340;35.2(20.2, 54.6)×10^(6)比28.4(24.1, 53.5)×10^(6)拷贝/L, Z=-0.10, P=0.920]。难治性CMV感染率为4.9%(7/143), 难治性CMV感染与非难治性CMV感染组间首次CMV-DNA的拷贝及治疗过程中的CMV-DNA拷贝峰值间差异均无统计学意义[21.8(13.1, 32.2)×10^(6)比25.9(14.2, 12.2)×10^(6)拷贝/L, Z=-1.04, P=0.299;47.7(27.9, 77.6)×10^(6)比27.7(19.7, 51.8)×10^(6)拷贝/L, Z=-1.49, P=0.137]。CMV感染组中减低强度预处理方案(RIC)的使用率、移植前受者CMV抗体阳性率、移植后Ⅱ~Ⅳ级急性移植物抗宿主病(aGVHD)发生率均明显高于未感染组[45.2%(14/31)比25.0%(28/112), 100%(31/31)比78.6%(88/112), 64.5%(20/31)比26.8%(30/112), χ^(2)=4.76、7.98、15.20, 均P<0.05]。本组患儿随访31.6(13.2, 45.9)个Objective To investigate the risk factors and outcomes of cytomegalovirus(CMV)infection post umbilical cord blood stem cell transplantation(UCBT)in children with primary immunodeficiency diseases(PID).Methods Clinical data of 143 PID children who received UCBT in the Children′s Hospital of Fudan University from January 2015 to June 2020 were collected retrospectively.CMV-DNA in the plasma was surveilled once or twice a week within 100 days post-UCBT.According to the CMV-DNA test results,children were divided into the CMV-infected group and the CMV-uninfected group.The incidence and risk factors of CMV infection were analyzed.At 1-month post-UCBT,the absolute lymphocyte count,ratio of lymphocyte subsets and immunoglobulin levels were compared between those whose CMV infection developed 1-month later post-UCBT and those not.Mann-Whitney U test and chi-squared test were used for comparision between groups.Kaplan-Meier survival analysis was used to analyze the impact of CMV infection on survival.Results Among 143 patients,there were 113 males and 30 females,with a age of 14(8,27)months at UCBT.Chronic granulomatosis disease(n=49),very-early-onset inflammatory bowel disease(n=43)and severe combined immunodefiency(n=29)were the three main kinds of PID.The rate of CMV infection was 21.7%(31/143),and the time of infection occurring was 44(31,49)days post-UCBT.The incidence of recurrent CMV infection was 4.2%(6/143)and refractory CMV infection was 4.9%(7/143).There was no significant difference in the first time CMV-DNA copy and peak CMV-DNA copy during treatment between the recurrent CMV infection group and the non-recurrent CMV infection group(32.8(18.3,63.1)×10^(6)vs.22.5(13.2,31.9)×10^(6) copies/L,Z=-0.95,P=0.340;35.2(20.2,54.6)×10^(6) vs.28.4(24.1,53.5)×106copies/L,Z=-0.10,P=0.920),so were those between the refractory CMV infection group and non-refractory CMV infection group(21.8(13.1,32.2)×10^(6) vs.25.9(14.2,12.2)×10^(6)copies/L,Z=-1.04,P=0.299;47.7(27.9,77.6)×10^(6) vs.27.7(19.7,51.8)×10^(6)copies/L,Z=-

关 键 词：巨细胞病毒 免疫缺陷综合征 脐血干细胞移植 儿童 

分 类 号：R725.9[医药卫生—儿科]