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:Thrombotic microangiopathy following chimeric antigen receptor T-cell therapy.
Thrombotic microangiopathy following chimeric antigen receptor T-cell therapy.
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血栓性微血管病(TMA)以微血管病性溶血性贫血为特征,与多种疾病状态及造血干细胞移植相关。CAR-T 细胞疗法是一种利用基因修饰的自体T细胞的新型免疫治疗方法。CAR-T 疗法已被发现与血管内皮损伤相关,但CAR-T 与TMA之间的直接关联尚未见报道。病例报告:本文报道了两例CAR-T 治疗后发生TMA的病例。每例患者在CAR-T 输注后2-3个月出现肾脏损伤、血小板减少和溶血性贫血的临床证据。我们描述了这些病例的临床经过、管理和结局。讨论/结论:CAR-T 细胞治疗相关TMA(CAR-T TMA)似乎是一个与移植相关TMA(TA-TMA)具有重叠临床特征的独立疾病实体。基于我们的初步临床观察,我们讨论了最佳的临床诊断/分类标准、潜在的病理生理机制以及明显自限性病程的意义。随着CAR-T 细胞治疗在血液系统恶性肿瘤中的应用日益增多,有必要开展系统性研究以改善CAR-T TMA的管理。
INTRODUCTION: Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia and is associated with a variety of conditions and following hematopoietic stem cell transplantation. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel immunotherapeutic approach using genetically modified autologous T cells.
CAR-T therapy has been linked with injuries to vascular endothelium, but a direct association between CAR-T and TMA has not been reported. CASE REPORTS: Two cases of TMAs following CAR-T treatment are reported here. In each case, clinical evidence of kidney injury, thrombocytopenia, and hemolytic anemia became apparent 2 - 3 months following CAR-T infusion.
We describe the clinical course, management, and outcome of these experiences. DISCUSSION/CONCLUSION: CAR-T cell therapy-associated TMA (CAR-T TMA) appear to be an entity that shares overlapping clinical features with transplant-associated TMA (TA-TMA).
Based on our preliminary clinical observations, we discuss the best clinical diagnosis/classification criteria, underlying pathophysiology, and the implication of the apparently self-limiting course. With increasing use of CAR-T cell treatment in hematologic malignancies, systematic studies will be necessary to improve management of CAR-T TMA.
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