Yang Yuanyuan, Peng Hongwei, Wang Jianxiang, Li Fei
Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Exp Hematol Oncol. 2024 Nov 9;13(1):110. doi: 10.1186/s40164-024-00573-9.
Chimeric antigen receptor (CAR) T-cell therapy represents a highly efficacious treatment modality demonstrated to enhance outcomes in patients afflicted with malignancies, particularly those enduring relapsed or refractory hematological malignancies. However, the escalating adoption of CAR T-cell therapy has unveiled several life-threatening toxicities, notably cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and hematological toxicities (HTs), thereby hindering the broad implementation of CAR T-cell therapy. HTs encompass a spectrum of adverse effects, including cytopenias, hemophagocytic lymphohistiocytosis (HLH), coagulopathies, and B-cell aplasia. While our comprehension of the underlying mechanisms governing CRS and ICANS is advancing, the intricate pathophysiology of HTs remains inadequately elucidated. Such knowledge gaps may precipitate suboptimal therapeutic decisions, potentially culminating in substantial medical resource depletion and detriment to patients' quality of life. In this comprehensive review, based on recent updated findings, we delineate various mechanisms contributing to HTs subsequent to CAR T-cell therapy, explicate manifestations of HTs, and proffer strategic interventions to mitigate this relevant clinical challenge.
嵌合抗原受体（CAR）T细胞疗法是一种高效的治疗方式，已证明可改善恶性肿瘤患者的治疗效果，尤其是那些患有复发或难治性血液系统恶性肿瘤的患者。然而，CAR T细胞疗法的日益广泛应用也揭示了几种危及生命的毒性反应，特别是细胞因子释放综合征（CRS）、免疫效应细胞相关神经毒性综合征（ICANS）、感染和血液学毒性（HTs），从而阻碍了CAR T细胞疗法的广泛实施。HTs包括一系列不良反应，如血细胞减少、噬血细胞性淋巴组织细胞增生症（HLH）、凝血功能障碍和B细胞发育不全。虽然我们对CRS和ICANS的潜在机制的理解正在不断深入，但HTs的复杂病理生理学仍未得到充分阐明。这些知识空白可能导致治疗决策欠佳，最终可能导致大量医疗资源的消耗，并损害患者的生活质量。在这篇全面综述中，基于最近的最新研究结果，我们阐述了CAR T细胞疗法后导致HTs的各种机制，解释了HTs的表现，并提出了应对这一相关临床挑战的策略性干预措施。
