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及时白细胞分离术可能影响高危 DLBCL 患者为 CAR-T 治疗采集淋巴细胞的“适应性”

英文原题:Timely Leukapheresis May Interfere with the "Fitness" of Lymphocytes Collected for CAR-T Treatment in High Risk DLBCL Patients.

查看英文原题

Timely Leukapheresis May Interfere with the "Fitness" of Lymphocytes Collected for CAR-T Treatment in High Risk DLBCL Patients.

PubMed 2022/10/27(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)-T细胞疗法的发展彻底改变了血液系统疾病的治疗。然而,约60%的患者在CAR-T 细胞治疗后复发,且尚未确定这一失败的明确原因。Bio-CAR-T BS研究(ClinicalTrials.gov:NCT05366569)的目的是加深我们对淋巴细胞采集的理解,以最大化CAR-T 细胞产品的质量。在入组的14例患者中,11例诊断为DLBCL,2例为PMBCL,1例为ALL。11例DLBCL患者中有5例符合“抢先”淋巴细胞单采的标准(处于第二次复发高风险),6例纳入标准治疗淋巴细胞单采组。既往自体干细胞移植(ASCT)和年龄在两组之间差异显著。在淋巴细胞单采时,“抢先”组患者的淋巴细胞更“健康”(更高的CD4+/CD8+比值;更高的na ve T细胞水平),与标准组相比,可能归因于ASCT的影响。

同时,年龄超过60岁也会导致更“耗竭”的淋巴细胞特征。总体而言,对复发高风险的DLBCL患者进行“抢先”Ly-单采似乎是可行的,并可能允许及时采集“健康”淋巴细胞用于CAR-T 细胞制造。

展开英文摘要原文

The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematological diseases.

However, approximately 60% of patients relapse after CAR-T cell therapy, and no clear cause for this failure has been identified. The objective of the Bio-CAR-T BS study (ClinicalTrials. gov: NCT05366569) is to improve our understanding of the lymphocyte harvest to maximize the quality of the CAR-T cell product. Of the 14 patients enrolled, 11 were diagnosed with DLBCL, 2 with PMBCL, and 1 with ALL. Five of 11 DLBCL patients met the criteria for "pre-emptive" Lymphocytes-apheresis (being at high risk of second relapse), and 6 were included in the standard-of-care Lymphocytes-apheresis group.

Previous autologous stem cell transplantation (ASCT) and age were significantly different between the two groups. At the time of Lymphocyte-apheresis, patients in the "pre-emptive" group had more "fit" lymphocytes (higher CD4+/CD8+ ratio; higher na ve T cells levels) compared with standard group, probably due to the impact of ASCT. At the same time, also being older than 60 years results in a more "exhausted" lymphocyte profile.

Overall, "pre-emptive" Ly-apheresis in DLBCL patients at high risk of relapse appears to be feasible and may allow the timely collection of "fit" lymphocytes for CAR-T cell manufacturing.

论文信息

作者
Farina M、Chiarini M、Almici C、Accorsi Buttini E、Zuccalà F、Piva S、Volonghi I、Poli L
单位
Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, 25123 Brescia, Italy.Italy
期刊
Cancers2022 Oct 27
原文标识
PubMed 36358694 · DOI 10.3390/cancers14215276