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 in pediatric patients undergoing CD19+CD22+ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia.
Infectious complications in pediatric patients undergoing CD19+CD22+ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia.
53 例患者发生 88 次感染。
CAR-T 细胞疗法可有效治疗复发/难治性急性 B 淋巴细胞白血病(R/R B-ALL),但患者易发生感染,这会显著损害长期生存和生活质量。本研究回顾分析本机构 79 例接受 CAR-T 治疗的儿童 R/R B-ALL 患者的感染并发症。共 53 例发生 88 次感染:9 例在淋巴细胞清除化疗期间发生 9 次感染;35 例在早期阶段(输注后第 0 至 30 天)发生 41 次感染;29 例在晚期阶段(输注后第 31 至 90 天)发生 38 次感染。31 次感染明确检出病原体,包括 23 种细菌、7 种病毒和 1 种真菌。4 例因感染入住重症监护病房,1 例死亡。单变量分析发现 10 项感染相关因素,包括肿瘤负荷、淋巴细胞清除化疗、中性粒细胞缺乏和淋巴细胞减少、细胞因子释放综合征(CRS)及免疫效应细胞相关神经毒性综合征(ICANS)等。多变量分析确认 3 级 CRS 是感染危险因素(风险比 2.41;95% 置信区间 1.08–5.36;P=0.031)。因此,积极降低 CRS 等级或可减少感染风险,改善患者长期生活质量。
Chimeric antigen receptor T-cell (CAR-T) therapy is effective in the treatment of relapsed/refractory acute B-lymphoblastic leukemia (R/R B-ALL); however, patients who receive CAR-T therapy are predisposed to infections, with considerable detrimental effects on long-term survival rates and the quality of life of patients. This study retrospectively analyzed infectious complications in 79 pediatric patients with R/R B-ALL treated with CAR-T cells at our institution. Overall, 53 patients developed 88 infections. Nine patients experienced nine infections during lymphodepletion chemotherapy, 35 experienced 41 infections during the early phase (days 0-+ 30 after infusion), and 29 experienced 38 infections during the late phase (day + 31-+ 90 after infusion). Pathogens were identified in 31 infections, including 23 bacteria, seven viruses, and one fungus. Four patients were admitted to the intensive care unit for infection and one died. In a univariate analysis, there were ten factors associated with infection, including tumor load, lymphodepleting chemotherapy, neutrophil deficiency and lymphocyte reduction, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), etc. In a multivariate analysis, CRS grade 3 was identified as a risk factor for infection (hazard ratio = 2.41, 95% confidence interval: 1.08-5.36, P = 0.031). Therefore, actively reducing the CRS grade may decrease the risk of infection and improve the long-term quality of life of these patients.
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