Objective: To observe the efficacy of chimeric antigen receptor T cell (CAR-T) in the treatment of children with refractory/recurrent B acute lymphocytic leukemia (B-ALL).
Methods: Thirty-two patients with r/r B-ALL were treated by CAR-T, the recurrence and death respectively were the end point events to evaluate the efficacy and safety of CAR-T.
Results: The median age of the patients was 7.5 (2-17.5) years old; 40 times CAR-T were received in all patients and the median number of CAR-T was 0.9×107/kg; efficacy evaluation showed that 2 cases died before the first evaluation. Thirty patients showed that 3, 6, and 9-moth RFS was (96.3±3.6)%, (81.4±8.6)% and (65.3±12.5)%, respectively, while 3, 6, and 9-month OS was all 100%, and 12, 24-month OS was (94.7±5.1)% and (76±12.8)%. BM blasts≥36% before reinfusion and ferritin peak≥2 500 ng/ml within two weeks of CAR-T cell reinfusion were associated with recurrence. Adverse reactions mainly included cytokine release syndrome (CRS) and CART-cell-related encephalopathy syndrome (CRES), CRS appeared in 26 patients within a week of CAR-T cell reinfusion. CRES reaction was detected in 12 patients. Eighteen patients received intravenous drip of tocilizumab, among them, 12 combined with glucocorticoid. CRS and CRES reactions were relieved within one week after treatment. Hormone dosage was related to the duration of remission in patients, and the cumulative dose of methylprednisolone≥8 mg/kg showed a poor prognosis.
Conclusion: CAR-T is a safe and effective treatment for r/r B-ALL, most CRS and CRES reactions are reversible. BM blasts ≥36% before reinfusion and cumulative dose of methylprednisolone ≥8 mg/kg after reinfusion both affect the therapeutic effect. Ferritin≥2 500 ng/ml within two weeks after reinfusion is related to disease recurrence and is an independent prognostic risk factor.
题目: 嵌合抗原受体T细胞治疗儿童难治/复发急性B淋巴细胞白血病的疗效.
目的: 观察嵌合抗原受体（CAR）T细胞治疗儿童难治/复发急性B淋巴细胞白血病（r/r B-ALL）的疗效及不良反应.
方法: 回顾性分析32例r/r B-ALL患儿行CAR-T细胞治疗的临床资料，分别以复发、死亡为终点事件，评估CAR-T细胞治疗r/r B-ALL的疗效及安全性.
结果: 2017年7月至2020年1月，共32例r/r B-ALL患儿接受CAR-T细胞治疗，中位年龄7.5（2-17.5）岁。32例患儿共回输CAR-T细胞40次，回输中位CAR-T细胞总量0.9×107/kg（患儿体重）。结果显示，2例患儿在评估前死亡，其余30例患儿3、6、9个月RFS分别为（96.3±3.6）%、（81.4±8.6）%和（65.3±12.5）%；3、6、9个月OS均为100%，12个月OS（94.7±5.1）%，24个月OS（76±12.8）%。回输前骨髓肿瘤负荷≥36%、CAR-T细胞回输2周内铁蛋白峰值≥2 500 ng/ml与复发相关。不良反应主要为细胞因子释放综合征（CRS）和CAR-T治疗相关脑病综合征（CRES），26例在CAR-T细胞回输1周内出现CRS反应，12例出现CRES反应。18例给予托珠单抗静滴，其中12例联合糖皮质激素，CRS反应及CRES反应经治疗后大多1周内缓解。激素使用剂量与患儿持续缓解时间相关，甲泼尼龙累积剂量≥8 mg/kg预后不佳.
结论: CAR-T细胞治疗儿童r/r B-ALL有效且安全，CRS及CRES反应经治疗后均可缓解；回输前骨髓肿瘤负荷≥36%、回输后甲泼尼龙累积剂量≥8 mg/kg预后不佳；回输后两周内铁蛋白峰值≥2 500 ng/ml与疾病复发相关，且为独立预后危险因素.
Keywords: child; chimeric antigen receptor T cell; refractory/recurrent B acute lymphocytic leukemia.