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:Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies.
Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies.
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嵌合抗原受体(CAR)T细胞疗法已彻底改变了血液系统恶性肿瘤的治疗格局。然而,该疗法常并发免疫效应细胞相关血液毒性(ICAHT),这是一种可能危及生命的不良事件,包括中性粒细胞减少、贫血和血小板减少。这些血细胞减少症增加了严重感染、输血依赖和住院时间延长的风险,对发病率和非复发死亡率有重大影响。本综述阐述了ICAHT的发生率、机制和危险因素,重点介绍了疾病负荷、患者免疫状态与CAR-T 细胞产品特征之间复杂的相互作用。基于中性粒细胞减少的深度和持续时间建立的标准化分级系统,改善了ICAHT的分类,并实现了更一致的风险分层。本文讨论了当前的预防和治疗策略,从生长因子的使用到对难治性病例进行造血干细胞支持,强调采用个体化方法来减轻严重和持续性血液毒性。这些管理策略凸显了需要有针对性的干预措施来预防ICAHT,同时不影响CAR-T 细胞的疗效。随着CAR-T 细胞疗法扩展到新的适应症,优化ICAHT管理可以改善患者预后、降低医疗资源利用并提高治疗的可及性。
Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for hematologic malignancies.
However, it is frequently complicated by immune effector cell-associated hematotoxicity (ICAHT), a potentially life-threatening adverse event encompassing neutropenia, anemia, and thrombocytopenia. These cytopenias elevate the risk of severe infections, transfusion dependence, and prolonged hospital stays, contributing substantially to morbidity and non-relapse mortality. This review delineates the incidence, mechanisms, and risk factors for ICAHT, highlighting the complex interplay between disease burden, a patient's immune status, and features of the CAR T-cell products.
Standardized grading systems, based on the depth and duration of neutropenia, have improved the classification of ICAHT and enabled more consistent risk stratification. Current prophylactic and therapeutic strategies, ranging from growth factor administration to hematopoietic stem cell boosts for refractory cases, are discussed, emphasizing tailored approaches to mitigate severe and prolonged hematotoxicity.
These management strategies highlight the need for targeted interventions to prevent ICAHT without compromising the efficacy of the CAR T cells. As CAR T-cell therapy broadens to new indications, optimized ICAHT management could enhance patients' outcomes, reduce healthcare utilization, and increase therapy accessibility.
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