贝林妥欧单抗治疗儿童B细胞型急性淋巴细胞白血病的安全性及疗效  

The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children

作　　者：李晓兰 赵贝贝 万扬 安文彬 刘芳 刘立鹏 王书春 戚本泉 刘天峰 刘晓明 阮敏 张丽 邹尧 陈晓娟 陈玉梅 郭晔 竺晓凡 杨文钰 Li Xiaolan;Zhao Beibei;Wan Yang;An Wenbin;Liu Fang;Liu Lipeng;Wang Shuchun;Qi Benquan;Liu Tianfeng;Liu Xiaoming;Ruan Min;Zhang Li;Zou Yao;Chen Xiaojuan;Chen Yumei;Guo Ye;Zhu Xiaofan;Yang Wenyu(Paediatric Haematology and Oncology Centre,State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin Institutes of Health Science,Tianjin 300020,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所)儿童血液与肿瘤诊疗中心,血液与健康全国重点实验室,国家血液系统疾病临床医学研究中心,细胞生态海河实验室,天津医学健康研究院,天津300020

出　　处：《中华医学杂志》2024年第27期2563-2567,共5页National Medical Journal of China

基　　金：中国医学科学院医学与健康科技创新工程(2023-I2M-C&T-B-106)

摘　　要：探讨贝林妥欧单抗在儿童CD19阳性(CD19+)B细胞型急性淋巴细胞白血病(B-ALL)的安全性及疗效。回顾性纳入中国医学科学院血液病医院自2021年8月至2023年10月接受贝林妥欧单抗治疗的B-ALL患儿,根据疾病状态将患儿分为难治/复发(RR)组、微小残留病清除(MC)组及化疗不耐受(IC)组。收集患儿的临床资料,评估药物不良反应、治疗疗效及患儿的生存情况。共纳入35例患儿,男20例,女15例,年龄0.6~16.4(9.9±4.2)岁;其中RR组10例,MC组20例,IC组5例。共完成56周期输注,其中完成1、2、3、4周期输注的患儿分别有24、5、2、4例;第1~4周期输注的中位时间[M(Q_(1),Q_(3))]分别为14(14,28)d、28(28,28)d、28(28,28)d和28(26,28)d。关于不良反应,1~2级细胞因子释放综合征(CRS)的发生率为57.1%(32/56),其中1级CRS占84.4%(27/32);免疫效应细胞相关神经毒性综合征(ICANS)发生率(4级)1.8%(1/56)。RR组中6例患儿治疗有效,微小残留病(MRD)均转阴,治疗前MRD水平均<20%,其中3例患儿在贝林妥欧单抗停药14~42 d后MRD再次转阳;4例患儿治疗无效,治疗前MRD均>20%。MC组治疗前MRD阳性者均转阴。IC组治疗前后MRD均为阴性。RR组治疗有效的患儿中位随访时间为5.7(3.8,9.4)个月,1年生存率及无事件生存率分别为40.0%±21.9%和33.3%±19.2%。MC组及IC组患儿中位随访时间分别为6.7(5.2,12.5)个月和7.1(5.1,7.6)个月,无事件生存率均为100%。贝林妥欧单抗在部分RR、MRD清除和化疗不耐受情况下应用的安全性及疗效良好。To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive(CD19+)B-cell acute lymphoblastic leukemia(B-ALL)in children.A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology&Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023.Based on their disease status,the patients were divided into refractory/relapsed(RR)group,minimal residual disease clearance(MC)group,and chemotherapy intolerance(IC)group.Clinical data of the children were collected to evaluate the adverse drug reactions,therapeutic efficacy and survival of the children.In total,35 patients were included,with 20 males and 15 females,aged from 0.6 to 16.4(9.9±4.2)years old.There were 10 cases in the RR group,20 cases in the MC group and 5 cases in the IC group.A total of 56 cycles of infusion were completed,with one cycle in 24 cases,two cycles in 5 cases,three cycles in 2 cases and four cycles in 4 cases.The median infusion time[M(Q_(1),Q_(3))]from the first to the fourth cycle was 14(14,28)days,28(28,28)days,28(28,28)days and 28(26,28)days,respectively.In terms of adverse reactions,the incidence of grade 1-2 cytokine release syndrome(CRS)was 57.1%(32/56),with grade 1 CRS accounting for 84.4%(27/32).The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS)(grade 4)was 1.8%(1/56).In the RR group,6 cases were treated effectively,and minimal residual disease(MRD)turned negative,before treatment,MRD levels were all less than 20%.Among them,3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab.Four cases were treated ineffectively,with MRD>20%before treatment.All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment.The median follow-up time of RR group was 5.7(3.8,9.4)months,and 1 year median survival rate and event-free survival rate were 40.0%±21.9%and 33.3%±19.2%,respective

关 键 词：白血病 幼淋巴细胞 B细胞 免疫治疗 治疗结果 儿童 

分 类 号：R733.71[医药卫生—肿瘤]