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- Title
The Clinical Significance of Circulating Lymphocytes Morphology in Diffuse Large B-Cell Lymphoma As Determined by a Novel, Highly Sensitive Microscopy.
- Authors
Fridberg, Gil; Horn, Galit; Globerson Levin, Anat; Benisty, Dan; Kay, Sigi; Glait-Santar, Chen; Perry, Chava; Ram, Ron; Avivi, Irit; Katz, Ben-Zion
- Abstract
Simple Summary: Chimeric Antigen Receptor T-cell (CAR T) therapy has become the preferable therapeutic approach in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Detection of CAR Ts in peripheral blood smear (PBS) is challenging due to the low sensitivity of current morphological technologies. We provide herein a morphological analysis of CAR Ts during the production process and in consecutive PBS obtained from DLBCL patients undergoing CAR T therapy, employing a novel, highly sensitive microscopy platform. We found that activated morphology was attributed predominantly to transduced cells following engagement with target cells. The average number of day 5 CAR Ts, and their sustained presence, were significantly higher in patients obtaining complete response. Also, a high number of CAR Ts was associated with longer cytokine storm release syndrome. These data indicate that CAR T morphological surveillance in PB might serve as a simple, fast and inexpensive method to provide clinically relevant insights. 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.
- Subjects
T cell anatomy; IN vitro studies; FLOW cytometry; STATISTICS; ACADEMIC medical centers; STAINS &; staining (Microscopy); MICROSCOPY; FERRITIN; SERUM; B cell lymphoma; BLOOD collection; ACQUISITION of data; MANN Whitney U Test; CYTOKINE release syndrome; DYNAMICS; TREATMENT effectiveness; CANCER patients; DESCRIPTIVE statistics; MEDICAL records; POSITRON emission tomography; TUMOR markers; ADVERSE health care events; CELL lines; DATA analysis software; RED blood cell transfusion; FRIEDMAN test (Statistics); DATA analysis
- Publication
Cancers, 2023, Vol 15, Issue 23, p5611
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers15235611