CELL INTELLIGENCE · 肿瘤细胞治疗研究

Chimeric antigen receptor T cell (CART) therapy toxicity includes cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), but also thrombotic and haemorrhagic events. Given the link between haemostasis and inflammation, haemostatic biomarkers could help identify at-risk patients. Sixty-two adult patients receiving CD19- or BCMA-targeted CART were prospectively included and followed up for 30 days to characterize haemostatic changes and evaluate their association with the risk of CRS, ICANS, thrombosis and bleeding. Blood samples were collected at baseline (pre-lymphodepletion), pre-infusion and on days + 3, + 14, and + 28 post-infusion. Haemostatic tests, including thrombin generation assay (TGA, ST-Genesia) and P-Selectin, were performed. CRS occurred in 94% of patients, ICANS in 39%, venous thrombosis in 1.6%, and clinically relevant bleeding in 13%. During follow-up, prolonged coagulation times, thrombocytopenia and decreased fibrinogen and P-selectin, were noted. Baseline endogenous thrombin potential (ETP) was associated with clinically relevant CRS risk (OR 12.39; p = 0.02) and baseline C-reactive protein (CRP) with ICANS (OR 1.66; p < 0.01). Baseline P-selectin levels and platelet count identified patients at higher bleeding risk (OR 0.20; p = 0.03 and OR 0.39; p < 0.01, respectively). In the first month after CART infusion, bleeding incidence exceeds thrombosis. TGA, CRP, platelet count and P-selectin may help identify patients at risk of severe toxicity, enabling earlier, targeted interventions.