自体移植联合抗CD19 CAR-T治疗难治性弥漫大B细胞淋巴瘤的临床观察研究

蒋瑛; 刘慧霞; 朱骏; 赵初娴; 李肃; 陈鸿林; 王椿

doi:10.13201/j.issn.1004-2806.2021.11.005

自体移植联合抗CD19 CAR-T治疗难治性弥漫大B细胞淋巴瘤的临床观察研究

- 上海闸新中西医结合医院血液科(上海, 200435)

详细信息

通讯作者: 王椿,E-mail:wangchunsgh@126.com

中图分类号: R733.4

收稿日期: 2021-03-23

Clinical observation study of autologous hematopoietic stem cell transplantation followed by anti-CD19 CAR-T for refractory diffuse large B-cell lymphoma

- Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital, Shanghai, 200435, China

More Information

Corresponding author: WANG Chun, E-mail: wangchunsgh@126.com

Received Date: 23 March 2021

摘要

摘要: 目的：评估难治性弥漫大B细胞淋巴瘤（DLBCL）患者接受自体移植和靶向CD19的嵌合抗原受体T细胞（抗CD19 CAR-T）治疗后的疗效和安全性。方法：纳入7例疾病进展的难治性ⅣB期DLBCL患者进行自体移植，自体干细胞回输后第4天回输自体共刺激因子为4-1BB的抗CD19 CAR-T细胞2.0×10⁶/kg（1.0×10⁶/kg~2.6×10⁶/kg）。结果：中位随访时间186（112~326） d，最佳疗效为3例达完全缓解，4例达部分缓解，总体反应率达100%。其中巨块型的最佳疗效均为部分缓解。随访终点总生存率71.4%，其中巨块型者总生存率66%，非巨块型者总生存率75%。中性粒细胞植入时间17（14~26） d。CAR-T开始扩增的时间与中位粒细胞植入时间呈正相关（r=0.884，P=0.008）。巨块型患者中CAR-T峰值出现的时间较非巨块型者晚（r=0.864，P=0.012）。细胞因子释放综合征发生率28.6%（2/7），无严重细胞因子释放综合征发生。结论：自体移植联合抗CD19 CAR-T方案可作为难治性DLBCL拯救性治疗的方法。
- 自体造血干细胞移植 /
- CAR-T /
- 弥漫大B细胞淋巴瘤 /
- CD19 /
- 细胞因子释放综合征
Abstract: Objective: To evaluate the efficacy and safety of autologous transplantation followed by CD19-targeted chimeric antigen receptor T cells(anti-CD19 CAR-T) therapy for refractory diffuse large B-cell lymphoma(DLBCL).Methods: Seven DLBCL patients with stage ⅣB were enrolled in this study. All the patients showed disease progression after multi-line treatment. Patients underwent autologous transplantation and followed by 2.0×10⁶/kg(1.0×10⁶/kg-2.6×10⁶/kg) 4-1 BB anti-CD19 CAR-T cells on days +4.Results: The median follow-up time was 186(112-326) days. Three of 7 cases achieved a best response of complete remission; 4 cases achieved best response of partial remission. The overall response rate reached 100%. Among them, the best curative effect of patients with bulky tumor was partial remission. The overall survival rate was 71.4%, among which 66% in bulky lymphoma and 75% in non-bulky lymphoma. The engraftment time of neutrophils was 17(14-26) days. The time of CAR-T expansion was positively correlated with the median time of neutrophil engraftment(r=0.884, P=0.008). It took longer to reach the peak of CAR-T cell expansion in bulky patients than that in non-bulky patients(r=0.864, P=0.012). Two of 7 cases(28.6%) experienced CAR-T cell-induced cytokine-release syndrome, and no severe cytokine-release syndrome occurred.Conclusion: Autologous transplantation followed by anti-CD19 CAR-T may be a salvage treatment for refractory DLBCL.
- autologous hematopoietic stem cell transplantation /
- CAR-T /
- diffuse large B-cell lymphoma /
- CD19 /
- cytokine-release syndrome

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