Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2023 May 8;14:1141779. doi: 10.3389/fimmu.2023.1141779. eCollection 2023.
Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable effects in treating various hematological malignancies. However, hematotoxicity, specifically neutropenia, thrombocytopenia, and anemia, poses a serious threat to patient prognosis and remains a less focused adverse effect of CAR-T therapy. The mechanism underlying lasting or recurring late-phase hematotoxicity, long after the influence of lymphodepletion therapy and cytokine release syndrome (CRS), remains elusive. In this review, we summarize the current clinical studies on CAR-T late hematotoxicity to clarify its definition, incidence, characteristics, risk factors, and interventions. Owing to the effectiveness of transfusing hematopoietic stem cells (HSCs) in rescuing severe CAR-T late hematotoxicity and the unignorable role of inflammation in CAR-T therapy, this review also discusses possible mechanisms of the harmful influence of inflammation on HSCs, including inflammatory abrasion of the number and the function of HSCs. We also discuss chronic and acute inflammation. Cytokines, cellular immunity, and niche factors likely to be disturbed in CAR-T therapy are highlighted factors with possible contributions to post-CAR-T hematotoxicity.
嵌合抗原受体 T 细胞（CAR-T）疗法在治疗各种血液恶性肿瘤方面显示出显著的效果。然而，血液毒性，特别是中性粒细胞减少症、血小板减少症和贫血症，对患者的预后构成严重威胁，仍然是 CAR-T 疗法较少关注的不良反应。在淋巴耗竭治疗和细胞因子释放综合征（CRS）的影响之后，持续或反复出现的晚期血液毒性的机制仍然难以捉摸。在这篇综述中，我们总结了 CAR-T 晚期血液毒性的现有临床研究，以阐明其定义、发生率、特征、危险因素和干预措施。由于输注造血干细胞（HSCs）在挽救严重的 CAR-T 晚期血液毒性方面的有效性，以及炎症在 CAR-T 疗法中的不可忽视作用，本综述还讨论了炎症对 HSCs 的有害影响的可能机制，包括炎症对 HSCs 的数量和功能的磨损。我们还讨论了慢性和急性炎症。在 CAR-T 治疗中可能被扰乱的细胞因子、细胞免疫和龛位因素是可能导致 CAR-T 后血液毒性的重要因素。
