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:Managing Treatment-Emergent Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome Following CAR-T Cell Therapy: A Case-Based Review of the use of Emapalumab.
Managing Treatment-Emergent Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome Following CAR-T Cell Therapy: A Case-Based Review of the use of Emapalumab.
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CAR-T(CAR-T)细胞疗法已经彻底改变了血液系统恶性肿瘤的治疗,在复发/难治性疾病患者中实现了高缓解率。尽管有这些获益,CAR-T 细胞疗法仍与独特毒性相关,包括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)、免疫细胞相关血液毒性(ICAHT)以及免疫效应细胞相关噬血细胞性淋巴组织细胞增多症样综合征(IEC-HS),后者以罕见且危及生命的高炎症反应为特征。本文报告1例56岁女性复发性套细胞淋巴瘤(MCL)患者,接受CAR-T 细胞疗法brexucabtagene autoleucel治疗后先后发生CRS和IEC-HS。初始治疗包括tocilizumab、糖皮质激素和阿那白滞素,随后同情使用emapalumab,一种干扰素-阻断剂。为提供更广泛的背景,我们进行了关于CAR-T 细胞相关毒性的文献综述,重点关注IEC-HS及其使用emapalumab的管理。临床和实验室表现,如铁蛋白水平升高、血细胞减少和器官功能障碍,是IEC-HS诊断标准的基础。需要警惕性监测和个体化治疗策略,以有效管理CAR-T 细胞疗法相关毒性,从而最大化其获益并最小化不良反应。在更严重的IEC-HS病例中,emapalumab可作为有效的靶向治疗使用。
Chimeric antigen receptor T (CAR-T) cell therapies have revolutionized the treatment of hematological malignancies, achieving high response rates in patients with relapsed or refractory disease. Despite these benefits, CAR-T cell therapies are associated with unique toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune cell-associated hematotoxicity (ICAHT), and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), which is characterized by a rare and life-threatening hyperinflammatory response. This paper presents a case of a 56-year-old woman with relapsed mantle cell lymphoma (MCL) treated with the CAR-T cell therapy, brexucabtagene autoleucel, who had subsequently developed CRS and later IEC-HS.
Initial management included tocilizumab, corticosteroids, and anakinra, followed by the compassionate use of emapalumab, an interferon- blocker. To provide broader context, we conducted a literature review of CAR-T cell-related toxicities, focusing on IEC-HS and its management with emapalumab.
Clinical and laboratory manifestations, such as elevated ferritin levels, cytopenias, and organ dysfunction, underpin the diagnostic criteria for IEC-HS. Vigilant monitoring and tailored therapeutic approaches are required to effectively manage toxicities associated with CAR-T cell therapy, to maximize its benefits and minimize adverse effects. In more severe IEC-HS cases, emapalumab may be used as an effective targeted therapy.
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