贝林妥欧单抗治疗儿童急性B淋巴细胞白血病10例临床分析

Clinical analysis of Belintoumab in the treatment of 10 children with acute B-lymphoblastic leukemia

目的探讨贝林妥欧单抗治疗儿童急性B淋巴细胞白血病(B-ALL)的安全性及有效性。方法回顾性分析2021年9月至2022年5月郑州大学第一附属医院收治并使用贝林妥欧单抗治疗的10例CD_(19)+ B-ALL患儿的临床资料。结果 10例患儿中, 复发6例, 初始治疗持续微小残留病(MRD)阳性3例, 合并侵袭性念珠菌病1例。治疗前2例骨髓原幼细胞≥0.25, 1例骨髓原幼细胞0.05~<0.25。7例骨髓完全缓解(CR), 其中6例MRD阳性, 1例MRD阴性。贝林妥欧单抗治疗后骨髓CR率为66.7%(2/3), 总MRD转阴率88.9%(8/9), 仅MRD阳性患儿转阴率为100%(6/6)。应用贝林妥欧单抗后随访中位时间4.1(1.6~10.0)个月, 总生存(OS)率为70.0%(7/10), 8例MRD阴性患儿均接受了造血干细胞移植, OS率为75%(6/8), 存活患儿至随访结束均未复发。最常见的不良反应为发热(90%, 9/10)及中性粒细胞减少(90%, 9/10), 1例(10%, 1/10)出现神经系统毒性表现为癫痫发作(2级), 1例(10%, 1/10)出现细胞因子释放综合征(2级), 经对症处理后均未影响治疗。结论贝林妥欧单抗治疗儿童复发/难治性CD_(19)+ B-ALL安全有效, 骨髓CR仅MRD阳性的患儿转阴率更高。贝林妥欧单抗也可作为不能耐受化疗CD_(19)+ B-ALL患儿的桥接方案。

Objective To investigate the safety and efficacy of Belintoumab on the treatment of children with acute B-lymphoblastic leukemia(B-ALL).Methods The clinical data of 10 children with CD_(19)+B-ALL who were admitted to the Department of Pediatrics,the First Affiliated Hospital of Zhengzhou University from September 2021 to May 2022 and treated with Belintoumab were analyzed retrospectively.Results Among the 10 cases,there were 6 recurrent cases,3 cases with persistent minimal residual disease(MRD)positive after an initial treatment,and 1 case complicated with invasive candidiasis.Before treatment,bone marrow blasts≥0.25,and that ranged 0.05-<0.25 were detected in 2 cases and 1 case,respectively.Seven cases had a complete remission(CR)of bone marrow,6 of which were MRD positive and 1 case was MRD negative.After treatment with Belintoumab,the CR rate was 66.7%(2/3).The overall MRD negative rate was 88.9%(8/9),and the negative rate in previously MRD positive children was 100%(6/6).The median follow-up time was 4.1(1.6-10.0)months after the application of Belintoumab.The overall survival(OS)rate was 70.0%(7/10).Eight MRD negative children received hematopoietic stem cell transplantation,and the OS rate was 75%(6/8).Survived children did not relapse until the last follow-up visit.Fever(90%,9/10)was the most common adverse events,followed by neutropenia(90%,9/10).One case(10%,1/10)of neurotoxicity was seizures(grade 2)and one case(10%,1/10)suffered cytokine release syndrome(grade 2),which did not influence the therapeutic efficacy of Belintoumab after symptomatic treatment.Conclusions Belintoumab is safe and effective on the treatment of children with recurrent/refractory CD_(19)+B-ALL,and those with MRD positive who have achieved CR in bone marrow have a higher rate of turning negative.Belintoumab can also be used as a bridge scheme for CD_(19)+B-ALL children who cannot tolerate chemotherapy.