AUTHOR=He Jinping , Xu Na , Zhou Hongsheng , Zhou Ya , Wu Di , Zhao Ruochong , Lin Tong , Xu Ju , Cao Rui , Li Peng , Liu Qifa 

TITLE=Case Report: Chimeric Antigen Receptor T Cells Induced Late Severe Cytokine Release Syndrome

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.893928

DOI=10.3389/fonc.2022.893928

ISSN=2234-943X

ABSTRACT=Objective: Severe cytokine release syndrome (sCRS) has emerged as an adverse complication in the early period of chimeric antigen receptor T cell (CART) therapy, while whether sCRS occurs in the late period remains unknown. Here, we aimed to elucidate the characterization of patients with late sCRS. 
Design: Patients diagnosed with relapsed or refractory B-cell malignancies were given fludarabine combining cyclophosphamide for lymphodepletion chemotherapy followed by CART. CAR-T cells in peripheral blood were monitored by quantitative PCR or flow cytometry. CRS was prospectively evaluated using the Penn criteria and reconciled with ASTCT CRS consensus grading system. 
Results: Patient one was administrated with CAR19/22 T-cell cocktail therapy and patient two received BCMA-targeted CART (BCMA-CART) therapy, respectively. 41 days and 163 days after CART infusion, two patients developed grade III CRS with the evidence of the CART remarkable re-expansion. 
Conclusion: Severe CRS could occur in the late period after CAR-T therapy as re-expansion of CAR T-cells possessed the potential risk for late sCRS.