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:Cardiotoxic Effects Following CAR-T Cell Therapy: A Literature Review.
Cardiotoxic Effects Following CAR-T Cell Therapy: A Literature Review.
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本文综述了关于CAR-T 细胞心脏毒性发生率、临床表现及危险因素的现有文献。
CAR-T 疗法自2017年获FDA批准以来,已成为治疗血液系统恶性肿瘤的突破性疗法。然而,CAR-T 疗法与一些副作用相关,中心脏毒性是显著关注点之一。迄今为止,关于CAR-T 心脏毒性的研究仅有少数几项,样本量有限,且研究结果异质性较大,难以得出普遍适用的结论。通过超声心动图、EKG和血液生物标志物测量,CAR-T 疗法与急性和亚急性心脏毒性的显著风险相关。细胞因子释放综合征(CRS)2级或以上的患者更可能出现心脏毒性。最常见的心脏事件包括需要升压药或血管加压药支持的 hypotension、心动过速、心力衰竭/失代偿、心房颤动、新发或加重的心肌病、心律失常、心肌炎、心脏骤停和心血管死亡。最常见的超声心动图变化为收缩功能障碍和舒张功能障碍,以及超声心动图异常发现。成人与儿童患者的研究结果存在差异。治疗后一年以上的长期影响在很大程度上仍未知,需要进行长期随访研究。
PURPOSE OF REVIEW: This paper reviewed the current literature on incidence, clinical manifestations, and risk factors of Chimeric Antigen Receptor T-cell (CAR-T) cardiotoxicity. RECENT FINDINGS: CAR-T therapy has emerged as a groundbreaking treatment for hematological malignancies since FDA approval in 2017. CAR-T therapy is however associated with a few side effects, among which cardiotoxicity is of significant concern. There were only a few studies on CAR-T cardiotoxicity published to date with limited sample sizes, and their findings were heterogeneous. It was difficult to reach generalizable conclusions. CAR-T therapy was associated with significant risks for acute and subacute cardiotoxicity, as measured by echocardiograms, EKG, and blood biomarkers.
Patients with cytokine release syndrome (CRS) grade 2 or higher were more likely to exhibit cardiotoxicity. The most prevalent cardiac events included hypotension-requiring inotropic or vasopressor support, tachycardia, heart failure/decompensation, atrial fibrillation, new or worsening cardiomyopathy, arrhythmia, myocarditis, cardiac arrest, and cardiovascular death.
The most prevalent echocardiographic changes were systolic dysfunction and diastolic dysfunction, and abnormal echocardiogram findings. There were differences in findings between adult and pediatric patients. The long-term effects beyond a year post treatment remain largely unknown and long-term follow-up studies are warranted.
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