IMR Press / FBL / Volume 28 / Issue 11 / DOI: 10.31083/j.fbl2811299
Open Access Original Research
Peripheral Blood Smears Distinguish Infective Fever after CAR-T Therapy
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1 Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430000 Wuhan, Hubei, China
2 Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 030032 Taiyuan, Shanxi, China
3 Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, 430030, China
4 Sino-German Joint Oncological Research Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, 030032 Taiyuan, Shanxi, China
*Correspondence: wangzq_427@163.com (Zhiqiong Wang); jiawei@tjh.tjmu.edu.cn (Jia Wei)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(11), 299; https://doi.org/10.31083/j.fbl2811299
Submitted: 31 March 2023 | Revised: 31 May 2023 | Accepted: 8 June 2023 | Published: 24 November 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Chimeric antigen receptor (CAR) T-cell therapy carries the risk of inducing severe and life-threatening toxicities such as cytokine release syndrome (CRS), neurotoxicity, and infection. Although CRS and infections have similar symptoms, their treatment strategies differ, and early diagnosis is very important. For CRS and infections, the fastest detection time currently takes more than 24 h, so a quick and simple method to identify a fever after CAR T-cell infusion is urgently needed. Methods: We enrolled 27 patients with recurrent fever treated with different types of CAR T-cells, including cluster of differentiation (CD) 7, CD19, CD22, and CD19-CD22 bicistronic CAR T-cells, and evaluated the infection events occurring in these patients. We detailed the morphology of CAR T-cells in peripheral blood smears (PBS) and reported the infection events, CAR transgene copy number, and inflammatory indicators within the first month after treatment. Results: Similar morphological characteristics were observed in the PBS of different CAR T-cells, namely, enlarged cell bodies, deep outside and shallow inside basophilic blue cytoplasm, and natural killer (NK) cell-like purplish red granules. There were ten infections in nine of the twenty-seven patients (33%). The percentage of atypical lymphocytes in PBS was significantly associated with CAR transgene copy number and absolute lymphocyte count in all patients. The atypical lymphocyte percentage was significantly higher in the non-infection group. Conclusions: In conclusion, the unique morphology of CAR T-cells in PBS can be used to evaluate CAR T-cell kinetics and provide reliable evidence for the rapid early identification of fever after CAR T-cell infusion. Clinical Trial Registrations: ChiCTR-OPN-16008526; ChiCTR-OPN-16009847; ChiCTR2000038641; NCT05618041; NCT05388695.

Keywords
chimeric antigen receptor T-cell therapy
peripheral blood smears
fever
infection
morphology
kinetics
Funding
82070217/National Natural Science Foundation of China
2021YFA1101502/National High Technology Research and Development Program of China
Figures
Fig. 1.
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