接受 CAR-T 细胞治疗的儿童中炎症相关蛋白和细胞因子的动力学——它们是治疗相关毒性的生物标志物吗？

CD19-targeted CAR-T cell therapy has revolutionized the treatment of relapsed/refractory (r/r) pre-B acute lymphoblastic leukemia (ALL).

However, it can be associated with acute toxicities related to immune activation, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokines released from activated immune cells play a key role in their pathophysiology.

This study was a prospective analysis of proinflammatory proteins and cytokines in children treated with tisagenlecleucel. Serial measurements of C-reactive protein, fibrinogen, ferritin, IL-6, IL-8, IL-10, IFN , and TNF were taken before treatment and on consecutive days after infusion. The incidence of CRS was 77. 8%, and the incidence of ICANS was 11. 1%. No CRS of grade 3 was observed. All complications occurred within 14 days following infusion. Higher biomarker concentrations were found in children with CRS grade 2.

Their levels were correlated with disease burden and CAR-T cell dose. While cytokine release syndrome was common, most cases were mild, primarily due to low disease burden before lymphodepleting chemotherapy (LDC). ICANS occurred less frequently but exhibited various clinical courses. None of the toxicities were fatal. All of the analyzed biomarkers rose within 14 days after CAR-T infusion, with most reaching their maximum around the third day following the procedure.