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成人和儿童癌症患者中 CAR-T 细胞治疗相关心脏毒性:临床评价

英文原题:Chimeric antigen receptor-T cell therapy-related cardiotoxicity in adults and children cancer patients: A clinical appraisal.

查看英文原题

Chimeric antigen receptor-T cell therapy-related cardiotoxicity in adults and children cancer patients: A clinical appraisal.

PubMed 2023/02/21(内容时间) Front Cardiovasc Med Q2 · IF 3(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

CAR-T(CAR-T)细胞疗法是一种创新免疫治疗方法,用于晚期和难治性肿瘤血液系统恶性肿瘤患者。输注表面表达嵌合受体的工程化 T 细胞可引发针对肿瘤细胞的免疫反应。然而,临床试验和观察性研究显示,CAR-T 输注会引起一系列不良事件,从轻微影响到危及生命的器官特异性并发症不等。特别是 CAR-T 相关心血管毒性已成为新兴不良事件类别,与患者发病率和死亡率升高相关。相关机制仍在研究中,但细胞因子释放综合征(CRS)中观察到的异常炎症活化似乎发挥关键作用。成人和儿童中最常报告的心脏事件包括低血压、心律失常和左心室收缩功能障碍,有时伴有明显心力衰竭。因此,亟需了解心脏毒性的病理生理基础及其发生相关风险因素,以确定最脆弱、需要密切心脏监测和长期随访的患者。本文旨在重点介绍 CAR-T 相关心血管并发症并阐明其发病机制,同时讨论监测策略、心脏毒性管理方案及这一快速发展领域的未来研究方向。

展开英文摘要原文

Chimeric antigen receptor-T (CAR-T) cells therapies represent an innovative immunological treatment for patients suffering from advanced and refractory onco-hematological malignancies. The infusion of engineered T-cells, exposing chimeric receptors on the cell surface, leads to an immune response against the tumor cells.

However, data from clinical trials and observational studies showed the occurrence of a constellation of adverse events related to CAR-T cells infusion, ranging from mild effects to life-threatening organ-specific complications. In particular, CAR-T cell-related cardiovascular toxicities represent an emerging group of adverse events observed in these patients, correlated with increased morbidity and mortality.

Mechanisms involved are still under investigation, although the aberrant inflammatory activation observed in cytokine release syndrome (CRS) seems to play a pivotal role. The most frequently reported cardiac events, observed both in adults and in the pediatric population, are represented by hypotension, arrhythmias and left ventricular systolic dysfunction, sometimes associated with overt heart failure.

Therefore, there is an increasing need to understand the pathophysiological basis of cardiotoxicity and risk factors related to its development, in order to identify most vulnerable patients requiring a close cardiological monitoring and long-term follow-up. This review aims at highlighting CAR-T cell-related cardiovascular complications and clarifying the pathogenetic mechanisms coming at play.

Moreover, we will shed light on surveillance strategies and cardiotoxicity management protocols, as well as on future research perspectives in this expanding field.

论文信息

作者
Camilli M、Maggio L、Tinti L、Lamendola P、Lanza GA、Crea F、Lombardo A
单位
Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy.Italy
文献类型
综述
期刊
Frontiers in cardiovascular medicine2023
原文标识
PubMed 36895831 · DOI 10.3389/fcvm.2023.1090103