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CD19嵌合抗原受体T细胞治疗22例B细胞淋巴瘤的疗效与安全性

[Efficacy and safety of CD19 chimeric antigen receptor T cells for the treatment of 22 patients with B-cell lymphoma].

作者信息

Xiao X, Jiang Y Y, Cao Y Q, Li Q, Jin X, Meng J X, Sui T, Li Y M, Zhao M F

机构信息

Tianjin First Central Hospital, Tianjin 300192, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2019 Apr 14;40(4):276-280. doi: 10.3760/cma.j.issn.0253-2727.2019.04.003.

Abstract

To investigate the efficacy and safety of CD19 chimeric antigen receptor T (CAR-T) lymphocytes for the treatment of B cell lymphoma. A total of 22 patients with B-cell lymphoma from February 1, 2017 to July 1, 2018 were reviewed to evaluate the efficacy and adverse reactions of CD19 CAR-T. Of 22 patients with B-cell lymphoma received CD19 CAR-T cells, the median dose of CAR-T cells was 7.2 (2.0-12.0) ×10/kg. Nine of 12 cases of relapse refractory patients were overall response. Complete remission (CR) occurred in 2 of 12 patients, partial remission (PR) in 7 of 12 patients. The overall response in minor residual disease positive (MRD) group was 8 of 10 patients. CD19 CAR-T cells proliferated in vivo and were detectable in the blood of patients. The peak timepoints of CAR-T cells proliferated in the relapsed refractory and MRD positive groups were 12 (5-19) and 4.5 (1-12) days after treatment respectively, and among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55%-24.74%) and 4.02% (2.23%-28.60%) of T lymphocytes respectively. The MRD positive patients achieved sustained remissions during a median follow-up of 8 months (rang 3-18 months) . None of all the patients relapsed during a median follow-up time of 10 months (3-18 months) . However, 7 PR responders of the relapsed refractory patients maintained a good condition for 1.5-6.0 months. One patient bridged to hematopoietic stem cell transplantation, another one sustained remission for 12 months. Cytokine-release syndrome (CRS) occurred in 14 patients with grade 1-2 CRS in MRD positive group and grade 3 CRS in relapsed refractory group. CAR-T cell therapy not only played a role in the rescue treatment of relapsed and refractory patients, but also produced a surprising effect in the consolidation and maintenance of B-cell lymphoma. CD19 CAR-T cells might be more effective in the treatment of MRD positive B-cell lymphoma patients than in the refractory or relapsed cases. High response rate was observed with fewer adverse reactions.

摘要

探讨CD19嵌合抗原受体T(CAR-T)淋巴细胞治疗B细胞淋巴瘤的疗效和安全性。回顾性分析2017年2月1日至2018年7月1日期间共22例B细胞淋巴瘤患者,评估CD19 CAR-T的疗效及不良反应。22例接受CD19 CAR-T细胞治疗的B细胞淋巴瘤患者中,CAR-T细胞的中位剂量为7.2(2.0 - 12.0)×10/kg。12例复发难治患者中有9例获得总体缓解。12例患者中2例完全缓解(CR),7例部分缓解(PR)。微小残留病阳性(MRD)组10例患者中有8例获得总体缓解。CD19 CAR-T细胞在体内增殖,可在患者血液中检测到。复发难治组和MRD阳性组CAR-T细胞增殖的峰值时间点分别为治疗后12(5 - 19)天和4.5(1 - 12)天,在外周血细胞中,CAR-T细胞分别占T淋巴细胞的10.10%(3.55% - 24.74%)和4.02%(2.23% - 28.60%)。MRD阳性患者在中位随访8个月(范围3 - 18个月)期间实现持续缓解。所有患者在中位随访时间10个月(3 - 18个月)内均未复发。然而,12例复发难治患者中的7例PR反应者病情维持良好1.5 - 6.0个月。1例患者过渡到造血干细胞移植,另1例持续缓解12个月。14例患者发生细胞因子释放综合征(CRS),MRD阳性组为1 - 2级CRS,复发难治组为3级CRS。CAR-T细胞疗法不仅在复发难治患者的挽救治疗中发挥作用,而且在B细胞淋巴瘤的巩固和维持治疗中也产生了惊人的效果。CD19 CAR-T细胞治疗MRD阳性B细胞淋巴瘤患者可能比难治或复发患者更有效。观察到高反应率且不良反应较少。

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