P1522: peripheral blood smears distinguish infective fever after car-t therapy

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Chimeric antigen receptor (CAR) T-cell therapy provides a better option for individuals with refractory or relapsed B-cell non-Hodgkin lymphoma (r/r B-NHL) and B-cell acute lymphoblastic leukemia (r/r B-ALL). Cytokine release syndrome (CRS) is most commonly observed toxicity, which are hard to distinguish from severe infection. Early identification between CRS and infections is important for providing appropriate managements and improving clinical outcome of these patients. Recent data suggest that morphologic findings on peripheral blood smear (PBS) can provide important clues to assess CAR-T kinetics. Aims: In this study, we investigated the characteristic of CAR-T cells in PBS when recipients experienced recurrent fever after CAR-T infusion, and combined conventional pathogen detection method and mNGS to investigate the cause of fever. combined with relevant clinical signs and symptoms. Methods: From May 2019 through November 2022, 27 patients (R/R B-ALL, n=6, R/R T-ALL, n=1, and R/R DLBCL, n=20) with recurrent fever (defined as body temperature above 38°C occur multiple times in the first months after CAR-T infusion) following CAR-T therapy within 1 month at Tongji Hospital of Huazhong University of Science and Technology in Wuhan, China were enrolled. The criteria for infection are defined as patients confirmed to carry a pathogen either by culture method or non-culture-based method, including nucleic acid detection/mNGS or antigen detection by conventional serological antibody assays. Results: Of the 27 receiving CAR-T infusion in this study, 10 patients on CD19 CAR-T, 1 on CD22 CAR-T, 10 on CAR19/22 “Cocktail” therapy, 5 on CD19-CD22 bicistronic CAR-T, and 1 on CD7 CAR-T therapy. 20/27 patients received CAR-T infusion following ASCT. All the 27 patients in the study experienced recurrent fever within 1 month after CAR-T cells infusion, the median days of first PBS were 9.4 days (mean 9.3 days; range 4-19). After CAR-T cells infusion, the lymphoblasts in all patients was decreased to 0% in their first PBS, with an increase of 2% to 85% atypical lymphocytes, and the percentage of atypical lymphocytes in PBS showed a positive correlation with the CAR transgene copy number and absolute lymphocyte count, suggesting that the expanding lymphocytes were entirely composed of CAR-T cells. In addition, the percentage of atypical lymphocytes in PBS was significantly higher in recipients without infection than in recipients with infection (P<0.05), and IL-6 was significant higher in recipients with infection (P<0.05). Furthermore, we observed similar morphological features of different CAR-T cells including CD7, CD19, CD22 CAR-T cells, that they showed enlarged cell bodies (about 4-5-fold higher than RBC), cells shape were irregular and monocyte-like, nuclei were blastoformation, round or irregular, indented, no folding, chromatin was loose, uneven distribution with small clumping, nucleoli were inconspicuous and pseudonucleolus may be seen, cytoplasm was abundant, light blue, markedly basophilic, and a dark blue cell edge, some azurophilic granules may be seen, and no vacuoles. Summary/Conclusion: In summary, our results show that PBS could as an indicator of CAR-T cells expansion and a quick and reliable method to identify causes of fever and in the early phase after CAR-T cells infusion.Keywords: Kinetics, Fever, CAR-T, Infection