化疗和(或)造血干细胞移植后儿童乙型病毒性肝炎疫苗再接种有效性及安全性研究  

Efficacy and safety of hepatitis B re-vaccination in children after completion of chemotherapy and(or)hematopoietic stem cell transplantation

作　　者：袁晴 周芬 张桦 曹清 陈文娟 费怡[3] 罗长缨[1] 高怡瑾[1] Yuan Qing;Zhou Fen;Zhang Hua;Cao Qing;Chen Wenjuan;Fei Yi;Luo Changying;Gao Yijin(Department of Hematology/Oncology,Shanghai Children′s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 20027,China;Department of Infectious Disease,Shanghai Children′s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 0017,China;Center for Diseases Control and Prevention of Pudong New District,Shanghai 20016,China)

机构地区：[1]上海交通大学医学院附属上海儿童医学中心血液/肿瘤科,200127 [2]上海交通大学医学院附属上海儿童医学中心感染科,200127 [3]上海市浦东新区疾病预防控制中心,200136

出　　处：《中华儿科杂志》2020年第10期802-806,共5页Chinese Journal of Pediatrics

摘　　要：目的评估接受化疗和(或)造血干细胞移植(HSCT)后患儿血清乙型病毒性肝炎(乙肝)表面抗体(HBsAb)水平及乙肝疫苗再接种的有效性和安全性。方法前瞻性研究。以2017年3月至2019年7月于上海儿童医学中心疫苗接种门诊就诊的完成化疗和(或)HSCT后患儿239例为研究对象,根据基础疾病分为白血病组(85例)、淋巴瘤组(30例)、实体瘤组(49例)和非恶性血液病组(75例)。根据基础疾病治疗方式分为化疗组(126例)、HSCT组(89例)和化疗+HSCT组(24例)。测定其治疗前后患儿血清HBsAb水平;对部分HBsAb阴性患儿进行3剂乙肝疫苗再接种,监测接种后疫苗相关不良反应,并于完成接种后1个月测定血清HBsAb水平。HBsAb滴度<10 U/L为阴性,≥10 U/L为阳性。采用χ²检验或Fisher精确检验比较组间HBsAb转阴率差异,并通过Logistic回归探讨HBsAb转阴的危险因素。结果入组239例患儿中男143例、女96例。化疗和(或)HSCT前,179例(74.9%)HBsAb阳性,60例(25.1%)HBsAb阴性;化疗和(或)HSCT结束后,具有乙肝保护性抗体的179例患儿中,133例(74.3%)HBsAb转为阴性;单因素分析显示不同基础疾病(χ^²=10.211,P=0.015)、治疗方式(χ^²=14.899,P<0.01)和治疗前HBsAb水平(χ^²=32.117,P<0.01)组患儿治疗后HBsAb转阴率差异有统计学意义。多因素Logistic回归分析发现,接受HSCT治疗[以化疗组为参照,比值比(OR)=2.999,95%可信区间(CI)1.276~7.050,P=0.012]和治疗前HBsAb低于328.2 U/L(以治疗前HBsAb≥328.2 U/L为参照,OR=6.397,95%CI3.159~12.954,P<0.01)是HBsAb转阴的危险因素。48例血清HBsAb阴性且接受乙肝疫苗再接种患儿中,47例(97.9%)HBsAb滴度转为阳性,且无严重不良反应发生。结论化疗和(或)HSCT治疗后,大部分患儿完全丧失对乙肝的保护性体液免疫。对其进行再接种可取得较高的转阳率,且具有较好的安全性,值得在此类人群中推广。Objective To assess the anti-hepatitis B surface antibody(HBsAb)titers in children after completion of chemotherapy and(or)hematopoietic stem cell transplantation(HSCT),evaluate the efficacy and safety of the current hepatitis B re-vaccination schedule.Methods A total of 239 children who completed their chemotherapy and(or)HSCT and visited the vaccination clinic of Shanghai Children′s Medical Center from March 2017 to July 2019 were enrolled in this study.According to the previous diseases,patients were divided into leukemia group(85 cases),lymphoma group(30 cases),solid tumor group(49 cases)and non-malignant hematological disease group(75 cases).According to the treatment of previous diseases,the patients were divided into chemotherapy group(126 cases),HSCT group(89 cases)and chemotherapy plus HSCT group(24 cases).HBsAb titers were assessed both at the time of diagnosis and after completion of treatment and some children who were HBsAb seronegative were re-vaccinated with 3 doses of hepatitis B vaccine,the vaccine-related adverse reactions were monitored.HBsAb titers were measured again one month after the completion of inoculation.HBsAb titers were defined as negative at levels<10 U/L and positive at≥10 U/L.Chi-square test or Fisher exact test was used to compare the difference of negative conversion rate of hepatitis B antibody between groups,and Logistic regression was used to explore the risk factors of hepatitis B antibody negative conversion.Results Among 239 patients,there were 143 males and 96 females.At the time of diagnosis,179 patients(74.9%)were HBsAb seropositive and 60 patients(25.1%)were HBsAb seronegative.After completion of chemotherapy and(or)HSCT,133 of 179 children with HBsAb seropositive(74.3%)at diagnosis became HBsAb seronegative.Univariate analysis showed significant differences at the negative conversion rates of HBsAb between different disease groups(χ^²=10.211,P=0.015),different treatments groups(χ^²=14.899,P<0.01)and different HBsAb titers groups before treatment(χ^²=32.117,

关 键 词：儿童 造血干细胞移植 肝炎 乙型 血清学免疫 

分 类 号：R725.1[医药卫生—儿科] R186[医药卫生—临床医学]