贝林妥欧单抗治疗儿童难治/复发前体B细胞急性淋巴细胞白血病的临床分析  

Clinical analysis of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia

作　　者：解姣 刘素香[1] 刘雨秋 张玉迪 吴茜桐 何海龙[1] 肖佩芳[1] 王易[1] 胡绍燕[1] 卢俊[1] Xie Jiao;Liu Suxiang;Liu Yuqiu;Zhang Yudi;Wu Xitong;He Hailong;Xiao Peifang;Wang Yi;Hu Shaoyan;Lu Jun(Department of Hematology,Children′s Hospital Affiliated to Soochow University,Suzhou 215000,China)

机构地区：[1]苏州大学附属儿童医院血液科,苏州215000

出　　处：《中华实用儿科临床杂志》2023年第9期707-712,共6页Chinese Journal of Applied Clinical Pediatrics

基　　金：江苏省卫生计生委医学科研课题(ZD2021006)。

摘　　要：目的评价贝林妥欧单抗治疗儿童难治/复发前体B细胞急性淋巴细胞白血病(R/R BCP-ALL)的临床疗效及安全性。方法采用回顾性研究的方法对2021年8月至2022年6月苏州大学附属儿童医院血液科使用贝林妥欧单抗治疗的R/R BCP-ALL患儿的临床资料进行分析。根据入院时患儿的体重分为<45 kg组和≥45 kg组,2组患儿分别接受不同剂量贝林妥欧单抗治疗,在15 d左右评估患儿骨髓缓解情况,同时监测治疗期间的临床指标及不良反应。采用两独立样本秩和检验比较组间差异,分类变量使用Fisher′s检验。结果16例R/R BCP-ALL患儿中,12例(75%)在14 d左右骨髓达完全缓解(CR)且微小残留病灶(MRD)转阴,其中骨髓原幼细胞比例≥0.5的9例患儿中有5例达到CR,<0.5有7/7例达到CR,达CR患儿的白细胞介素6(IL-6)峰值显著高于未达CR者(Z=2.50,P=0.012)。12例在第15天左右骨髓评估达CR,3例未达CR的在第28天评估仍未缓解,疗效预测准确度为93.8%(15/16)。不良反应包括发热、中性粒细胞减少、血钾降低、肝功能异常、血钙减低、水肿、皮疹、高血压、心肌损害、腹痛和低血压、细胞因子释放综合征(均为1级),无神经毒性的发生,且无一例因治疗发生死亡。结论贝林妥欧单抗治疗儿童R/R BCP-ALL缓解率高,尤其在低肿瘤负荷中疗效更为显著;不良反应小且可控;第15天是患儿疗效评估的最佳时机;较高的IL-6峰值可作为预测疗效的指标之一。Objective To evaluate the clinical efficacy and safety of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia(R/R BCP-ALL)in children.Methods Clinical data of children with R/R BCP-ALL treated with Blinatumomab in the Department of Hematology,Children′s Hospital of Soochow University,from August 2021 to June 2022 were retrospectively analyzed.Children were divided into<45 kg group and≥45 kg group according to their weight at admission.They were treated with different dosages of Blinatumomab,and bone marrow remission was assessed at about 15 days.Clinical indicators and adverse events during the treatment period were recorded.The rank sum test of two independent samples were used to compare the differences between groups.The Fisher′s test was used for comparing categorical variables.Results Among the 16 children with R/R BCP-ALL,12 cases(75%)achieved complete response(CR)and minimal residual lesion(MRD)turned negative at about 14 days.Among them,5 out of 9 children with bone marrow primitive naive cell ratio≥0.5 achieved CR,and 7/7 children with bone marrow primitive naive cell ratio<0.5 achieved CR.The peak value of interleukin-6(IL-6)in children with CR was significantly higher than those without CR(Z=2.50,P=0.012).Twelve cases achieved CR on bone marrow assessment around day 15,and 3 cases who did not achieve CR remained in remission on day 28,with an efficacy prediction accuracy of 93.8%(15/16).Adverse events included fever,neutropenia,hypokalemia,abnormal liver function,hypocalcemia,edema,rash,hypertension,myocardial damage,abdominal pain,hypotension,and cytokine release syndrome,which were all grade 1.Neurotoxicity and death were not reported.Conclusions The remission rate of R/R BCP-ALL in children treated with Blinatumomab was high,especially in patients with a low tumor load.The toxicity and adverse events of Blinatumomab treatment are minor and controllable.Day 15 is the optimal time point to evaluate the efficacy of Blinatumomab on children with

关 键 词：贝林妥欧单抗 儿童 急性淋巴细胞白血病 难治 复发 

分 类 号：R733.71[医药卫生—肿瘤]