Department of Clinical Laboratory, First Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
J BUON. 2021 Jan-Feb;26(1):159-165.
To explore the efficacy of chimeric antigen receptor (CAR)-T cell therapy in children with relapsed or refractory acute B-lymphocytic leukemia (B-ALL) and the influencing factors for their prognosis.
A retrospective analysis was performed on the clinical data of 46 children with relapsed or refractory B-ALL, who were admitted to and treated in our hospital from January 2015 to October 2017, and the remission and post-infusion adverse reactions were observed in all the patients. Besides, the survival of the patients was followed up and recorded, and the influencing factors for the prognosis were identified by univariate and multivariate Cox regression analyses.
Bone marrows were routinely monitored after infusion of CAR-T cells. It was found that 35 children patients achieved morphologic complete remission, had a lower level of minimal residual disease (MRD) than that before treatment and exhibited a response rate of 76.1%, of whom there were 33 cases of MRD-negative remission. Different degrees of cytokine release syndrome (CRS) occurred in 41 out of 46 children, consisting of 37 (80.4%) cases of grade I-II CRS and 4 (8.7%) cases of grade III-IV CRS. The concentrations of serum interleukin (IL)-6, interferon-γ (IFN-γ), ferritin and C-reactive protein (CRP) obviously rose during CRS, and their peak values in the patients with grade III-IV CRS were notably higher than those in grade I-II CRS patients (p<0.001). At the end of follow-up, the median follow-up time was 28.2 months, and the 3-year overall survival (OS) and event-free survival (EFS) rates were 28.3% and 13.0%, respectively. The results also showed that tumor burden ≥5% prior to CAR-T cell therapy [hazard ratio (HR) =3.496, 95% confidence interval (CI) =1.448-9.891, p=0.014] and non-combination with hematopoietic stem cell transplant (HSCT) therapy (HR =0.890, 95% CI =0.543-0.904, p=0.025) were independent risk factors for the prognosis of the patients.
Anti-cluster of classification (CD) 19 CAR-T cell therapy is safe and efficacious against relapsed or refractory B-ALL in children. Reducing the tumor burden before infusion of CAR-T cells and combined with HSCT after infusion are independent factors for improving the prognosis of the patients.
探讨嵌合抗原受体（CAR）-T 细胞疗法治疗复发/难治性急性 B 淋巴细胞白血病（B-ALL）的疗效及影响预后的因素。
回顾性分析 2015 年 1 月至 2017 年 10 月在我院接受治疗的 46 例复发/难治性 B-ALL 患儿的临床资料，观察所有患儿的缓解情况及输注后不良反应，随访并记录患儿生存情况，采用单因素和多因素 Cox 回归分析影响预后的因素。
CAR-T 细胞输注后常规监测骨髓，发现 35 例患儿获得形态学完全缓解，微小残留病（MRD）水平低于治疗前，缓解率为 76.1%，其中 33 例 MRD 阴性缓解。46 例患儿中，41 例出现不同程度的细胞因子释放综合征（CRS），其中 37 例（80.4%）为Ⅰ-Ⅱ级 CRS，4 例（8.7%）为Ⅲ-Ⅳ级 CRS。CRS 时血清白细胞介素（IL）-6、干扰素-γ（IFN-γ）、铁蛋白和 C 反应蛋白（CRP）浓度明显升高，其中Ⅲ-Ⅳ级 CRS 患儿的峰值明显高于Ⅰ-Ⅱ级 CRS 患儿（p<0.001）。随访结束时，中位随访时间为 28.2 个月，患儿 3 年总生存率（OS）和无事件生存率（EFS）分别为 28.3%和 13.0%。结果还显示，CAR-T 细胞治疗前肿瘤负荷≥5%[风险比（HR）=3.496，95%置信区间（CI）=1.448-9.891，p=0.014]和未联合造血干细胞移植（HSCT）治疗（HR=0.890，95%CI=0.543-0.904，p=0.025）是影响患儿预后的独立危险因素。
抗 CD19 CAR-T 细胞疗法治疗儿童复发/难治性 B-ALL 安全有效，输注前降低肿瘤负荷，输注后联合 HSCT 是改善患儿预后的独立因素。
