CELL INTELLIGENCE · 肿瘤细胞治疗研究

Chimeric antigen receptor (CAR) T-cell therapy has significantly improved outcomes in patients with relapsed/refractory aggressive large B-cell lymphoma (R/R LBCL). Although thrombosis and bleeding complications have been increasingly reported, their clinical relevance and risk factors remain unclear, also due to heterogeneity between reporting studies. We investigated the incidence of thrombosis and bleeding in a more homogeneous real-world multicenter cohort by analyzing 250 adults with R/R LBCL who were included in the Dutch "Follow that CAR!" multicenter registry, and all received axicabtagene ciloleucel (axi-cel) CAR T-cell therapy. We assessed the impact of thrombosis and bleeding, incorporated as time-dependent covariates on overall survival and explored associations with cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), anticoagulant therapy, and laboratory parameters. One-year cumulative incidences of thrombosis and bleeding were 6.3% and 11.0%, respectively. Median time to thrombosis or bleeding was 28 days after infusion for both events. Bleeding was associated with poorer overall survival (hazard ratio [HR] 3.77, 95% CI 1.96-7.27). Patients with a CAR-HEMATOTOX score 2 before CAR T-cell therapy (HR 3.62, 95% CI 1.23-10.69), therapeutic anticoagulation at time of infusion (HR 3.74, 95% CI 1.33-10.49), or thrombocytopenia grade 3 (platelet count < 50 10 9 /L) at time of infusion (HR 3.55, 95% CI 1.12-11.26, P = 0.03) had a significantly higher risk of bleeding. Our study confirms the high risk and clinical relevance of bleeding in patients receiving CAR T-cell therapy. Prospective studies are necessary to confirm these results and to guide recommendations regarding modifiable risk factors such as the use of anticoagulation or transfusion thresholds during CAR T-cell therapy.