决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Infectious Complications Following CD30 Chimeric Antigen Receptor T-Cell Therapy in Adults.
复发/难治性淋巴瘤患者接受 CD19.CAR T 细胞治疗后的临床定义感染发生率在 CAR-T 细胞治疗后的第一年为 60-90%,并且是非复发死亡最常见的原因。
背景:感染日益被认为是CAR-T治疗常见并发症。复发/难治淋巴瘤接受CD19 CAR-T后首年临床感染率为60%至90%,且是非复发死亡最常见原因;其他靶点后的感染风险了解较少。本文首次报告霍奇金淋巴瘤和外周T细胞淋巴瘤患者接受CD30 CAR-T后的感染情况。研究者推测,由于CD30仅在部分活化T/B细胞表达,其感染发生率和严重程度会低于CD19 CAR-T。回顾单中心2016至2021年64例CD30 CAR-T患者,并与同期50例CD19 CAR-T患者比较输注后一年感染。两组微生物学确诊感染率均为36%。CD19组感染严重程度较高且细菌感染更多;CD30组较常见1级呼吸道病毒感染。结果为新型CD30 CAR-T产品提供感染类型和严重程度比较基准;仍需更大队列验证,并可为CD30 CAR-T抗菌预防指南提供参考。
UNLABELLED: Infections are increasingly recognized as a common complication of chimeric antigen receptor (CAR) T-cell therapy. The incidence of clinically-defined infection after CD19.CAR T-cell therapy for relapsed/refractory lymphoma ranges from 60-90% in the first year after CAR T-cell therapy and is the most common cause for non-relapse mortality. However, infectious risk after CAR T-cell therapy targeting other malignancies is not well understood. Herein, we report for the first time, infectious complications after CD30.CAR T-cell treatment for patients with Hodgkin's lymphoma and peripheral T-cell lymphoma. Since CD30 is only expressed on a subset of activated T and B-cells, we hypothesized that CD30.CAR T-cell patients would have reduced incidence and severity of infections after infusion compared to CD19.CAR T-cell patients. We retrospectively evaluated all 64 patients who received CD30.CAR T-cells at a single institution between 2016-2021, and assessed infections within one year after cell infusion, comparing these data to a contemporary cohort of 50 patients who received CD19.CAR T-cells at the same institution between 2018-2021. 23 CD30.CAR T-cell patients (36%) and 18 CD19.CAR T-cell patients (36%) developed a microbiologically confirmed infection. Infection severity and bacterial infections were higher in the CD19.CAR T-cell group compared to CD30.CAR T-cell recipients who more commonly had grade 1 respiratory viral infections. Our data reflect expected outcomes for severity and infection type in CD19.CAR T-cell patients and provide a benchmark for comparison with the novel CD30.CAR T-cell product. Although our findings require replication in a larger cohort, they have implications for antimicrobial prophylaxis guidelines after CD30.CAR T-cell therapy. KEY POINTS: 1) The incidence of infections within the first year after CD30.CAR T-cell therapy was equivalent to that following CD19.CAR T-cell therapy2) Viral infections were more common after CD30.CAR T-cell therapy but bacterial infections predominated after CD19.CAR T-cell therapy.
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