探讨贝林妥欧单抗治疗儿童复发/难治CD19⁺急性B淋巴细胞白血病(R/R CD19⁺ B-ALL)的疗效及安全性。

选择2021年3月至2022年7月郑州大学附属儿童医院收治的使用贝林妥欧单抗方案治疗的6例R/R CD19⁺ B-ALL患儿(患儿1~6)为研究对象。评估其使用贝林妥欧单抗治疗的疗效、安全性和主要结局指标，包括骨髓细胞形态学检查、微小残留白血病(MRD)、融合基因，贝林妥欧单抗治疗相关不良反应等。本研究遵循的程序符合郑州大学附属儿童医院伦理委员会制定的伦理学标准，得到该委员会批准(伦审号：2021-H-K43)，所有患儿的治疗方案均取得患儿监护人的知情同意。

对患儿1~6采用贝林妥欧单抗治疗的疗效、安全性和主要结局指标如下。①多重巢式聚合酶链反应(PCR)检测骨髓细胞检查融合基因结果：患儿1~6中，共检测到4种常见融合基因表达，包括患儿1、2、6的E2A-PBX1基因和患儿4的TEL-AML基因、患儿5的MLL-AF10基因、患儿3的BCR/ABL。②疗效：治疗前，3例(患儿1、2、6)患儿骨髓细胞形态学缓解，骨髓MRD及融合基因阳性，治疗后，2例(患儿1、2)骨髓MRD及融合基因均转阴，1例(患儿6)均未缓解；治疗前，1例(患儿3)患儿骨髓细胞形态学缓解、MRD<0.01%及融合基因呈阳性，治疗后，融合基因转阴；治疗前，1例(患儿4)骨髓细胞形态学缓解、MRD呈阳性及融合基因呈阴性，治疗后，MRD转阴；治疗前，1例(患儿5)骨髓细胞形态未缓解、MRD及融合基因呈阳性，治疗后，均有下降但未达到完全缓解(CR)。③治疗安全性：患儿1~6患儿在贝林妥欧单抗输注后3 d内均出现发热，考虑为1~2级细胞因释放综合征(CRS)。其中2例(患儿4、5)减低剂量后发热消退；1例(患儿4)在输注第3天出现发热未进行剂量调整时，出现发热抽搐，停药后抽搐停止，体温恢复正常。

贝林妥欧单抗对儿童R/R CD19⁺ B-ALL有效，尤其是对于骨髓形态缓解、骨髓MRD呈阳性的患儿疗效更显著，为后续桥接异基因造血干细胞移植(allo-HSCT)提供机会。该治疗的主要不良反应为发热，但是减低剂量后发热可缓解，未监测到药物导致的严重不良反应。

To observe the efficacy and safety of blinatumomabin in the treatment of children with relapsed/refarctory CD19-positive B-cell acute lymphoblastic leukaemia (R/R CD19⁺ B-ALL).

The clinical data of children with R/R CD19⁺ B-ALL treated with blinatumomabin in Children′s Hospital Affiliated to Zhengzhou University from March 2021 to July 2022 were retrospectively analyzed, and the efficacy and safety of blinatumomabin were evaluated. Main outcome endpoints included bone marrow morphology, minimal residual disease (MRD), fusion gene, and adverse reaction. The procedure followed in this study was in accordance with the regulations of the Ethics Committee of Children′s Hospital Affiliated to Zhengzhou University, and was reviewed and approved by the Ethics Committee (Approval No. 2021-H-K43). All the treatment schemes for children have obtained the informed consent of their guardians.

①Four common fusion genes were detected in 6 children, including E2A-PBX1 (3 cases), TEL-AML (1 case), MLL-AF10 (1 case), and BCR/ABL (1 case). ②Before treatment, 3 cases (Patient 1, 2, 6)had morphological bone marrow remission, and were flow cytometry minimal residual disease (MRD) and fusion gene positive, including 2 cases (Patient 1, 2) with MRD and fusion gene turned negative, and 1 case (Patient 6) with no remission after treatment. Before the treatment, 1 case (Patient 3) had morphological bone marrow remission, MRD<0.01%, and fusion gene positive, and after the treatment, fusion gene turned negative. Before treatment, there was 1 case (Patient 4) of morphological bone marrow remission, positive MRD and fusion gene negative, and after treatment, MRD turned negative. Before treatment, 1 case (Patient 5) had no remission for bone marrow morphology and was positive for MRD and fusion gene, which all decreased after treatment but did not achieve complete remission (CR). ③Regarding the safety analysis, all 6 children had fever during the first three days of treatment, which was considered to be Grade 1-2 cytokine release syndrome (CRS). Of these, 2 cases (Patient 4, 5) had fever resolved after dose reduction; 1 case (Patient 5) had fever on the third day of treatment without dose adjustment, and then developed fever convulsions, which resolved after drug withdrawal; the body temperature of 3 febrile children with the fever duration of 1-3 days returned to normal after symptomatic management.

Children with R/R CD19⁺ B-ALL often developed a fever during the initial treatment of blinatumomab, which was considered to be Grade 1-2 CRS. According to the condition of children, the fever was relieved by dose reduction. In addition, blinatumomab is quite effective for children who had morphological bone marrow remission and were MRD positive.