The correlation factors and prognostic significance of coagulation disorders after chimeric antigen receptor T cell therapy in hematological malignancies: a cohort study
Rujiao Dong, Yudi Wang, Yuanyuan Lin, Xiaohong Sun, Chongyun Xing, Yu Zhang, Haizhi Wang, Lihui Dai, Yu Kang, Songfu Jiang
Abstract
Background: Along with cytokine release syndrome (CRS) and neurotoxicity, coagulation disorder is a common early complication of chimeric antigen receptor (CAR)-T cell therapy. However, the mechanisms and prognostic significance of CAR-T-related coagulation disorders are not fully known. This study explored the possible correlation factors and prognostic significance of coagulation disorders after CAR-T cell infusion in patients with relapsed/refractory hematological malignancies. Methods: -test and Spearman correlation coefficient. The prognostic significance of coagulation disorders was analyzed using Kaplan-Meier method and stepwise multivariate Cox regression model. Results: The incidence of coagulation disorders was 59% within 1 month of CAR-T cell infusion. PT prolongation, APTT prolongation, TT prolongation, and D-dimer increase peaked at a median of 6-9 days, and fibrinogen decreased to its lowest value at a median of 12 days. Coagulation disorders in patients with severe CRS were more significant (P<0.001). Abnormality of coagulation parameters was closely related to cytokines, CAR-T cells, liver function parameters, and von Willebrand Factor (VWF) in both peak level and peak time (P<0.05). Statistical analysis showed that coagulation disorders were associated with higher initial response rates (TT, P=0.006; D-dimer, P=0.010) and also longer progression-free survival (PFS) (PT, P=0.017; APTT, P=0.018; TT, P=0.001; Fibrinogen, P=0.003; D-dimer, P<0.001) in CAR-T therapy, with TT prolongation (HR =0.279, 95% CI: 0.099-0.782, P=0.015) and D-dimer increase (HR =0.218, 95% CI: 0.087-0.548, P=0.001) independent predictors for PFS. Conclusions: The protection of liver and endothelial cells may reduce CAR-T-related coagulation disorders. Further, coagulation disorders occurring within 1 month of CAR-T cell infusion can serve as a new predictor for prognosis in patients with hematological malignancies.