Li Qing, Mu Juan, Yuan Jijun, Yang Zhenxing, Wang Jia, Deng Qi
Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, People's Republic of China.
Medical Department, Shanghai Genbase Biotechnology Co., Ltd, Shanghai 201203, People's Republic of China.
Onco Targets Ther. 2020 Nov 9;13:11471-11484. doi: 10.2147/OTT.S277146. eCollection 2020.
To investigate the donor chimerism changes and curative effects associated with the use of autologous anti-CD19 chimeric antigen receptor (CAR) T cells with B-cell acute lymphoblastic leukemia (B-ALL) presenting with a low donor chimerism level and relapse after allogeneic hematopoietic stem cell transplant (allo-HSCT).
Nine patients with B-ALL showing low donor chimerism level and relapse after allo-HSCT were enrolled. Patients 1-3 received CD19 CAR-T cell therapy using cells derived from autologous peripheral blood mononuclear cells (PBMCs) (comprising a mixture of patient and original donor cells) as their donors could not provide PBMCs. Samples from the other six patients (Patients A-F) were investigated only in vitro. The changes in the degree of donor chimerism, function of the CD19 CAR-T cells and T cells in all nine patients were analyzed in vitro. The therapeutic effects and adverse events (AEs) were also evaluated in Patients 1-3.
The CAR-T cells and T cells in all nine patients showed complete donor chimerism restoration following a 12-day culture period in vitro. These CD19 CAR-T cells demonstrated strong cytotoxicity towards Nalm 6 cells in vitro except in patients 3 and D. In the latter patients, the absolute numbers of all subsets, especially the CD8 + T-cell absolute numbers in peripheral blood were very low. Patients 3 and D showed relatively short durations from transplant to recurrence and received chemotherapy after relapse. In the patients receiving CD19 CAR-T cell therapy, the most commonly observed AE was grade 1 to 2 cytokine release syndrome. None of the cases showed acute graft-versus-host disease during treatment. Patients 1 and 2 achieved complete response with complete restoration of donor chimerism. Patient 3, who received the same CD19 CAR-T cell therapy, did not respond to this therapy.
CD19 CAR-T cells derived from patients relapsed after allo-HSCT with a low level of donor chimerism were effective for salvage therapy and could restore to complete donor chimerism after 12 days' culture in vitro.
Humanized CD19 CAR-T cell therapy for relapse or refractory B-cell lymphoma or acute B lymphocytic leukemia, ChiCTR1800019622, Registered 24 November 2018, http://www.chictr.org.cn/index.aspx.
探讨自体抗CD19嵌合抗原受体（CAR）T细胞用于供体嵌合水平低且异基因造血干细胞移植（allo-HSCT）后复发的B细胞急性淋巴细胞白血病（B-ALL）患者时的供体嵌合变化及疗效。
纳入9例allo-HSCT后供体嵌合水平低且复发的B-ALL患者。1-3号患者因供体无法提供外周血单个核细胞（PBMC），故使用源自自体PBMC（包含患者和原始供体细胞的混合物）的细胞接受CD19 CAR-T细胞治疗。其他6例患者（A-F号患者）的样本仅进行体外研究。对所有9例患者体外分析供体嵌合程度变化、CD19 CAR-T细胞和T细胞功能。对1-3号患者评估治疗效果及不良事件（AE）。
所有9例患者的CAR-T细胞和T细胞在体外培养12天后均显示供体嵌合完全恢复。这些CD19 CAR-T细胞除3号患者和D号患者外，在体外对Nalm 6细胞均表现出强细胞毒性。在这两名患者中，所有亚群的绝对数量，尤其是外周血中CD8 + T细胞的绝对数量非常低。3号患者和D号患者从移植到复发的时间相对较短，复发后接受了化疗。在接受CD19 CAR-T细胞治疗的患者中，最常观察到的AE为1-2级细胞因子释放综合征。治疗期间无一例出现急性移植物抗宿主病。1号和2号患者实现完全缓解，供体嵌合完全恢复。接受相同CD19 CAR-T细胞治疗的3号患者对此治疗无反应。
源自allo-HSCT后复发且供体嵌合水平低的患者的CD19 CAR-T细胞对挽救治疗有效，体外培养12天后可恢复至完全供体嵌合。
人源化CD19 CAR-T细胞治疗复发或难治性B细胞淋巴瘤或急性B淋巴细胞白血病，ChiCTR1800019622，2018年11月24日注册，http://www.chictr.org.cn/index.aspx 。
