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供体来源的 CAR-T 疗法与供体淋巴细胞输注相比,可提高异基因移植后复发 B-ALL 的生存率。

Donor-derived CAR-T therapy improves the survival of relapsed B-ALL after allogeneic transplantation compared with donor lymphocyte infusion.

机构信息

Department of Hematology, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Guangzhou, Guangdong, China.

Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China.

出版信息

Hum Cell. 2023 Sep;36(5):1716-1728. doi: 10.1007/s13577-023-00934-2. Epub 2023 Jul 7.

DOI:10.1007/s13577-023-00934-2
PMID:37418233
Abstract

Chimeric antigen receptor (CAR)-T cell therapy revolutionized treatment for various hematologic malignances. However, limited studies were reported to compare the efficacy and safety of CAR-T and donor lymphocyte infusion (DLI) for patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after hematopoietic stem cell transplantation (HSCT) comprehensively. We conducted a single-center, retrospective comparative study that consisted of 12 patients who were treated with DLI (control group) and 12 patients treated with donor-derived CD19 CAR-T cells (experimental group, 6 patients also received CD22 or CD123 CAR-T cells sequentially) with 3 overlaps. The event-free survival (EFS) of patients in experimental group was superior to that of the control group: 516 days versus 98 days (p = 0.0415). Compared with 7 of 12 patients treated with DLI suffered grades III-IV acute graft versus host disease (aGVHD), one grade III aGVHD developed in patients treated with CAR-T therapy. No significant difference in the incidence of infection was identified between these two groups. Most patients in the experimental group had only mild cytokine release syndrome and none developed neurotoxicity. The univariate analysis of patients in the experiment group revealed that earlier CAR-T therapy for post-transplantation relapse was associated with better EFS. There was no significant difference in EFS between patients treated with dual-target CAR-T with those with single CD19 CAR-T. In this study, our data supported that donor-derived CAR-T therapy is a safe and potentially effective treatment for relapsed B-ALL after HSCT and may be superior to DLI.

摘要

嵌合抗原受体 (CAR)-T 细胞疗法彻底改变了各种血液恶性肿瘤的治疗方法。然而,关于 CAR-T 与供者淋巴细胞输注(DLI)治疗造血干细胞移植(HSCT)后复发 B 细胞急性淋巴细胞白血病(B-ALL)患者的疗效和安全性,仅有有限的研究进行了报道。我们进行了一项单中心、回顾性对比研究,共纳入 12 例接受 DLI(对照组)和 12 例接受供体来源 CD19 CAR-T 细胞治疗(实验组,6 例患者还先后接受 CD22 或 CD123 CAR-T 细胞治疗)的患者,其中 3 例重叠。实验组患者的无事件生存(EFS)优于对照组:516 天与 98 天(p=0.0415)。与 12 例接受 DLI 治疗的患者中 7 例发生 III-IV 级急性移植物抗宿主病(aGVHD)相比,接受 CAR-T 治疗的患者仅发生 1 例 III 级 aGVHD。两组间感染发生率无显著差异。实验组大多数患者仅发生轻微细胞因子释放综合征,无一例发生神经毒性。实验组患者的单因素分析显示,移植后复发后早期进行 CAR-T 治疗与更好的 EFS 相关。接受双靶点 CAR-T 治疗与接受单靶点 CD19 CAR-T 治疗的患者在 EFS 方面无显著差异。在这项研究中,我们的数据支持供体来源的 CAR-T 治疗是 HSCT 后复发 B-ALL 的一种安全且潜在有效的治疗方法,可能优于 DLI。

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Donor-derived and off-the-shelf allogeneic anti-CD19 CAR T-cell therapy for R/R ALL and NHL: A systematic review and meta-analysis.供体来源和现成的同种异体抗 CD19 CAR T 细胞疗法治疗 R/R ALL 和 NHL:系统评价和荟萃分析。
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