文章：

循环淋巴细胞形态在弥漫性大B细胞淋巴瘤中的临床意义——基于新型高灵敏度显微镜的测定

The Clinical Significance of Circulating Lymphocytes Morphology in Diffuse Large B-Cell Lymphoma As Determined by a Novel, Highly Sensitive Microscopy

原文发布日期：28 November 2023

DOI: 10.3390/cancers15235611

类型: Article

开放获取: 是

英文摘要：

Chimeric Antigen Receptor T-cell (CAR T) therapy has become the preferable treatment in relapsed/refractory diffuse large B-cell lymphomas (DLBCL) patients. Detection of CAR Ts in peripheral blood smear (PBS) is challenging due to insufficient data regarding their morphology and low sensitivity. The morphological evolution of CAR Ts along their production process, and in patients, was established by Full-Field Morphology (FFM), a novel digital microscopy approach that provides highly sensitive PBS analysis. At day 8 of production, 42.7 ± 10.8% of the CAR T transduced cells exhibited activated morphology compared with 9.3 ± 3.8% in untransduced cells. Moreover, engagement of transduced CAR Ts with target cells resulted in further morphological transformation into activated morphology (83 ± 5.6% of the cells). In patients, the average number of day 5 CAR Ts, and their sustained presence, were significantly higher in patients obtaining complete response. A high number of activated morphology CAR Ts at day 14 was associated with prolonged cytokine release storm. Overall, CAR Ts exhibited heterogeneous morphology, with the activated morphology attributed predominantly to transduced cells following engagement with target cells. Post-transfusion CAR T detection was associated with increased complete responses. FFM CAR T surveillance in PBS may serve as a simple inexpensive method to provide clinically relevant insights into this treatment modality.

摘要翻译： 

嵌合抗原受体T细胞（CAR T）疗法已成为复发/难治性弥漫性大B细胞淋巴瘤（DLBCL）患者的优选治疗方案。由于缺乏关于其形态学的充分数据及检测灵敏度较低，在外周血涂片（PBS）中检测CAR T细胞具有挑战性。本研究通过全视野形态学分析（FFM）——一种可提供高灵敏度PBS分析的新型数字显微技术，系统阐述了CAR T细胞在生产过程中及患者体内的形态演变规律。在生产第8天，42.7 ± 10.8%的CAR T转导细胞呈现活化形态，而未转导细胞中该比例仅为9.3 ± 3.8%。此外，转导CAR T细胞与靶细胞结合后，进一步形态转化为活化形态的比例达83 ± 5.6%。在临床患者中，获得完全缓解的患者其第5天CAR T细胞平均数量及持续存在时间均显著更高。第14天高比例的活化形态CAR T细胞与延长的细胞因子释放风暴持续时间相关。总体而言，CAR T细胞呈现异质性形态特征，其中活化形态主要出现在转导细胞与靶细胞结合后。输注后CAR T细胞的检测与完全缓解率提升相关。基于FFM的PBS CAR T监测可作为一种简便经济的方法，为这种治疗模式提供具有临床意义的监测指标。

原文链接：

The Clinical Significance of Circulating Lymphocytes Morphology in Diffuse Large B-Cell Lymphoma As Determined by a Novel, Highly Sensitive Microscopy