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嵌合抗原受体 T 细胞治疗中细胞因子释放综合征的特征和危险因素。

Characteristics and Risk Factors of Cytokine Release Syndrome in Chimeric Antigen Receptor T Cell Treatment.

机构信息

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Key Laboratory of Bone Marrow Stem Cell, Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.

出版信息

Front Immunol. 2021 Feb 23;12:611366. doi: 10.3389/fimmu.2021.611366. eCollection 2021.

Abstract

Clinical trials have confirmed that chimeric antigen receptor (CAR) T cell therapies are revolutionizing approaches for treating several relapsed or refractory hematological tumors. Cytokine release syndrome (CRS) is an adverse event with high incidence during CAR-T treatment. A further understanding of the characteristics and related risk factors of CRS is important for effective management. A total of 142 patients with relapsed or refractory acute lymphocyte leukemia (ALL), lymphoma, or multiple myeloma (MM) received lymphodepletion chemotherapy followed by infusion of CAR-T cells. The characteristics of CRS at different time points after treatment were monitored and risk factors were analyzed. The incidence of CRS for ALL, lymphoma, and multiple myeloma were 82%, 90%, and 90% respectively. Fever was observed on a median of day 3 for ALL, day 1 for lymphoma, and day 8.5 for MM after CAR-T cell infusion, and the duration was different between grade 1-2 CRS and grade 3-5 CRS. Disease types, peak concentration of IL-6, and CRP were associated with CRS. For patients with ALL, numbers of lymphoblast in bone marrow before lymphodepletion, peak concentration of IL-6, and CRP were independent risk factors of CRS. Clinical stage of lymphoma patients and high tumor burden in marrow of MM patients were independent risk factors of CRS. In conclusion, the characteristics and risk factors of CRS in different B-cell hematological tumors are different and should be managed individually during CAR-T cell therapy.

摘要

临床试验已经证实,嵌合抗原受体(CAR)T 细胞疗法正在彻底改变治疗几种复发或难治性血液系统肿瘤的方法。细胞因子释放综合征(CRS)是 CAR-T 治疗期间高发生率的不良事件。进一步了解 CRS 的特征和相关危险因素对于有效管理至关重要。共有 142 例复发或难治性急性淋巴细胞白血病(ALL)、淋巴瘤或多发性骨髓瘤(MM)患者接受淋巴细胞耗竭化疗,然后输注 CAR-T 细胞。监测治疗后不同时间点 CRS 的特征,并分析危险因素。ALL、淋巴瘤和 MM 的 CRS 发生率分别为 82%、90%和 90%。在 CAR-T 细胞输注后,ALL 的中位发热时间为第 3 天,淋巴瘤为第 1 天,MM 为第 8.5 天,1-2 级 CRS 和 3-5 级 CRS 的持续时间不同。疾病类型、IL-6 和 CRP 的峰值浓度与 CRS 相关。对于 ALL 患者,淋巴细胞耗竭前骨髓中淋巴母细胞的数量、IL-6 和 CRP 的峰值浓度是 CRS 的独立危险因素。淋巴瘤患者的临床分期和 MM 患者骨髓中的高肿瘤负荷是 CRS 的独立危险因素。总之,不同 B 细胞血液系统肿瘤的 CRS 特征和危险因素不同,在 CAR-T 细胞治疗期间应单独管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6f5/7940756/9c9b74a35c68/fimmu-12-611366-g001.jpg

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