CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Infections following chimeric antigen receptor T cell therapy: 2018-2022.
Infections following chimeric antigen receptor T cell therapy: 2018-2022.
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COVID-19 和艰难梭菌感染是 CAR-T 细胞治疗后最常见的感染。大多数感染发生在最初 100 天内。在 CRS/ICANS 患者中,经验性抗生素使用和艰难梭菌感染很常见,且无记录的细菌感染,因此为这一人群的抗菌药物管理提供了极好的机会。
嵌合抗原受体(CAR)T细胞疗法是治疗复发/难治性血液系统恶性肿瘤的一种新兴治疗方式。CAR-T 细胞疗法后的感染并发症尚未明确。
这是一项对2018年4月至2022年12月期间在底特律Karmanos癌症中心接受CAR-T 细胞治疗的患者数据的回顾性分析。患者数据收集至其最后一次已知的诊所或住院随访就诊。感染事件定义为任何微生物学证实或临床记录在案的感染。
76例患者接受了FDA批准的CAR-T 细胞产品治疗。33例患者(43.4%)至少发生过一次感染事件。在中位随访184(96-340)天期间,共发生61次感染事件。感染发生的中位时间为59(22-209)天。细菌感染和病毒感染分别占感染事件的42.6%和41%。COVID-19是最常见的感染性并发症(14.8%)。时间-事件分析显示,大多数感染发生在前100天内。在未证实细菌感染的情况下,因细胞因子释放综合征/免疫效应细胞相关神经毒性综合征(CRS/ICANS)而经验性使用抗生素的患者占85.7%。艰难梭菌占所有感染事件的11.5%。6例艰难梭菌感染患者中有5例患有CRS/ICANS并接受了抗生素治疗。
Chimeric antigen receptor (CAR) T-cell therapy is an emerging therapeutic modality for relapsed and refractory hematological malignancies. Infectious complications following CAR T-cell therapy are not well defined.
This is a retrospective analysis of data on patients who received CAR T-cell therapy between April 2018 and December 2022 at the Karmanos Cancer Center, Detroit. Patients' data were collected up to their last known clinic or inpatient follow-up visit. An infectious episode was defined as any microbiologically proven or clinically documented infection.
Seventy-six patients received therapy with FDA-approved CAR T-cell products. Thirty-three patients (43.4%) had at least one infectious episode. There were 61 infectious episodes during a median follow-up of 184 (96-340) days. Median duration for the onset of infection was 59 (22-209) days. Bacterial and viral infections occurred in 42.6% and 41% of the infectious episodes, respectively. COVID-19 was the most common infectious complication (14.8%). Time-to-event analysis showed that most infections occurred within the first 100 days. Empirical antibiotic use during Cytokine Release Syndrome/Immune effector Cell-Associated Neurotoxicity Syndrome (CRS/ICANS) in the absence of documented bacterial infection was reported in 85.7% of patients. Clostridioides difficile accounted for 11.5% of all infectious episodes. Five of six patients with C. difficile infection had CRS/ICANS and received antibiotics.
COVID-19 and C. difficile infection were the most common infections following CAR T-cell therapy. Most infections occurred within the first 100 days. Empiric antibiotic use and C. difficile infection were common in patients with CRS/ICANS, in the absence of documented bacterial infection, thus providing an excellent opportunity for antimicrobial stewardship in this population.
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