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:Cytokine-based models for efficient differentiation between infection and cytokine release syndrome in patients with hematological malignancies.
Cytokine-based models for efficient differentiation between infection and cytokine release syndrome in patients with hematological malignancies.
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尽管嵌合抗原受体 (CAR)-T 细胞疗法的疗效已被广泛证实,但其副作用的复杂性和致命性阻碍了其临床应用。细胞因子释放综合征 (CRS) 是 CAR-T 细胞输注后最常见的毒性,其症状与感染症状高度重叠。
然而,当前感染的诊断技术耗时长且敏感性不高。因此,我们旨在开发可行且高效的模型,以优化临床实践中的鉴别诊断。本研究纳入本中心的 191 例发热患者,包括 85 例 CRS 相关发热和 106 例感染性发热。通过利用发热高峰时的血清细胞因子谱,我们分别使用分类树算法和逐步 logistic 回归分析生成了鉴别模型。第一个模型使用了三种细胞因子(IFN-γ、CXCL1 和 CXCL10),并显示出高敏感性(训练集 90%,验证集 100%)和高特异性(训练集 98.44%,验证集 90.48%)。五细胞因子模型(CXCL10、CCL19、IL-4、VEGF 和 CCL20)也显示出高敏感性(训练集 91.67%,验证集 95.65%)和高特异性(训练集 98.44%,验证集 100%)。这些可行且准确的鉴别模型可能促进免疫治疗期间感染的早期诊断,从而能够早期且适当地干预。
Although the efficacy of chimeric antigen receptor (CAR)-T cell therapy has been widely demonstrated, its clinical application is hampered by the complexity and fatality of its side effects. Cytokine release syndrome (CRS) is the most common toxicity following CAR-T cell infusion, and its symptoms substantially overlap with those of infection. Whereas, current diagnostic techniques for infections are time-consuming and not highly sensitive.
Thus, we are aiming to develop feasible and efficient models to optimize the differential diagnosis in clinical practice.
This study included 191 febrile patients from our center, including 85 with CRS-related fever and 106 with infectious fever. By leveraging the serum cytokine profile at the peak of fever, we generated differential models using a classification tree algorithm and a stepwise logistic regression analysis, respectively. The first model utilized three cytokines (IFN- , CXCL1, and CXCL10) and demonstrated high sensitivity (90% training, 100% validation) and specificity (98.
44% training, 90. 48% validation) levels. The five-cytokine model (CXCL10, CCL19, IL-4, VEGF, and CCL20) also showed high sensitivity (91. 67% training, 95. 65% validation) and specificity (98. 44% training, 100% validation). These feasible and accurate differentiation models may prompt early diagnosis of infections during immune therapy, allowing for early and appropriate intervention.
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