The Efficacy And Safety Of Chimeric Antigen Receptor T Cells In The Treatment Of Relapsed/refractory B-cell Acute Lymphoblastic Leukemia

Objective: To evaluate the efficacy and safety of chimeric antigen receptor T cells(CAR-T)therapy in the treatment of relapse/refractory B-cell acute lymphoblastic leukemia(B-ALL)and analyze the correlative impart factors.Methods: The study retrospectively analyzes the clinical data of 55 patients with relapsed/refractory B-ALL who received CAR-T therapy at our center from June 2016 to June 2019.The clinical efficacy and related adverse events were analyzed.Results: Among all 54 evaluable patients,48 patients achieved complete remission30 days after CAR-T treatment,with a complete remission rate of 88.9%.The relative higher tumor burden and serum LDH level before lymphodepletion chemotherapy were associated with failure of CAR-T therapy.The most common adverse events observed was cytokine release syndrome(CRS).After receiving CAR-T treatment,47 patients experienced different grades of CRS,and overall incidence rate of CRS was 85.5%.Compared to the patients received CD19 CAR-T,the patients received CD19/CD22 dual-targeting CAR-T therapy had lower incidence rate of 3/4 grade CRS.Remarkably,the peak levels of IL-6,IL-10,IFN-γ,PT,APTT and D-dimer during CRS were positively correlated with CRS grade,with significant differences between mild CRS group and severe CRS group.Similarly,the nadir value of fibrinogen was negatively correlated with CRS grade,and was lower in severe CRS group than that of mild group.In patients developed severe CRS,levels of IL-6,IL-10,IFN-γ,PT,APTT and D-dimer were significantly increased in the early stage after CAR-T infusion,and the changes in coagulation function indicators were in line with the changes of multiple cytokines.Conclusion: The study demonstrated that CAR-T cell therapy could effectively and safely treat relapsed/refractory B-ALL patients.Significant elevation of multiple cytokines or abnormal of coagulation function indicators in the early stages after CAR-T infusion suggest the risk of severe CRS.Early and timely intervention of severe CRS contributes a lot to improve the safety of CAR-T treatment.