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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Mucormycosis after CD19 chimeric antigen receptor T-cell therapy: results of a US Food and Drug Administration adverse events reporting system analysis and a review of the literature.
Mucormycosis after CD19 chimeric antigen receptor T-cell therapy: results of a US Food and Drug Administration adverse events reporting system analysis and a review of the literature.
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嵌合抗原受体(CAR)T细胞疗法可使复发性B细胞恶性肿瘤获得持久缓解,但治疗相关免疫抑制导致非典型感染引起显著发病和死亡风险。毛霉病是一种侵袭性强且具有侵袭性的真菌感染,在血液系统恶性肿瘤患者中死亡风险为40-80%。在这篇大查房中,我们报告一例接受CAR-T 细胞疗法的54岁患者的毛霉病病例,通过联合积极外科清创、抗真菌药物治疗和逆转潜在危险因素,实现了对毛霉目的完整临床控制,但因广泛口面部手术导致显著并发症,影响患者言语和吞咽。为提供更广泛背景,我们将该病例与美国食品药品监督管理局不良事件报告数据库分析及文献综述一起呈现,以全面评估接受CAR-T 细胞疗法患者中毛霉病的临床负担。
我们讨论流行病学、临床特征、诊断工具以及当前的治疗和预防框架。我们进行该分析是为了促进CAR-T 细胞疗法专科医生和微生物学家对毛霉病提高警惕,并说明早期启动治疗以有效管理该病的重要性。通过针对最高风险患者的靶向监测和霉菌预防以及毛霉目特异性筛查检测,毛霉病的预防和早期诊断可能是改善接受CAR-T 细胞疗法患者结局的关键。
Chimeric antigen receptor (CAR) T-cell therapy leads to durable remissions in relapsed B-cell cancers, but treatment-associated immunocompromise leads to a substantial morbidity and mortality risk from atypical infection. Mucormycosis is an aggressive and invasive fungal infection with a mortality risk of 40-80% in patients with haematological malignancies.
In this Grand Round, we report a case of mucormycosis in a 54-year-old patient undergoing CAR T-cell therapy who reached complete clinical control of Mucorales with combined aggressive surgical debridement, antifungal pharmacotherapy, and reversal of underlying risk factors, but with substantial morbidity from extensive oro-facial surgery affecting the patient's speech and swallowing.
For broader context, we present our case alongside an US Food and Drugs Administration adverse events reporting database analysis and a review of the literature to fully evaluate the clinical burden of mucormycosis in patients treated with CAR T-cell therapy.
We discuss epidemiology, clinical features, diagnostic tools, and current frameworks for treatment and prophylaxis.
We did this analysis to promote increased vigilance for mucormycosis among physicians specialising in CAR T-cell therapy and microbiologists and to illustrate the importance of early initiation of therapy to effectively manage this condition. Mucormycosis prevention and early diagnosis, through targeted surveillance and mould prevention in patients at highest risk and Mucorales-specific screening assays, is likely to be key to improving outcomes in patients treated with CAR T-cell therapy.
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