Genetically engineered chimeric antigen receptor (CAR) T cells have become an effective treatment option for several advanced B-cell malignancies. Haematological side-effects, classified in 2023 as immune effector cell-associated haematotoxicity (ICAHT), are very common and can predispose for clinically relevant infections. As haematopoietic reconstitution after CAR T-cell therapy differs from chemotherapy-associated myelosuppression, a novel classification system for early and late ICAHT has been introduced. Furthermore, a risk stratification score named CAR-HEMATOTOX has been developed to identify candidates at high risk of ICAHT, thereby enabling risk-based interventional strategies. Therapeutically, growth factor support with granulocyte colony-stimulating factor (G-CSF) is the mainstay of treatment, with haematopoietic stem cell (HSC) boosts available for patients who are refractory to G-CSF (if available). Although the underlying pathophysiology remains poorly understood, translational studies from the past 3 years suggest that CAR T-cell-induced inflammation and baseline haematopoietic function are key contributors to prolonged cytopenia. In this Review, we provide an overview of the spectrum of haematological toxicities after CAR T-cell therapy and offer perspectives on future translational and clinical developments.

中文翻译：

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CAR T 细胞治疗后免疫效应细胞相关的血液毒性：从机制到管理


基因工程嵌合抗原受体 (CAR) T 细胞已成为多种晚期 B 细胞恶性肿瘤的有效治疗选择。血液学副作用在 2023 年被归类为免疫效应细胞相关血液毒性 (ICAHT)，非常常见，可能导致临床相关感染。由于 CAR T 细胞治疗后的造血重建不同于化疗相关的骨髓抑制，因此引入了一种新的早期和晚期 ICAHT 分类系统。此外，还开发了名为 CAR-HEMATOTOX 的风险分层评分，以识别 ICAHT 高风险患者，从而实现基于风险的干预策略。在治疗上，生长因子支持和粒细胞集落刺激因子 (G-CSF) 是治疗的支柱，对于 G-CSF 难治的患者可以使用造血干细胞 (HSC) 加强治疗（如果有的话）。尽管其潜在的病理生理学仍知之甚少，但过去 3 年的转化研究表明，CAR T 细胞诱导的炎症和基线造血功能是导致血细胞减少时间延长的关键因素。在这篇综述中，我们概述了 CAR T 细胞治疗后的血液学毒性范围，并对未来的转化和临床发展提出了展望。