神经元损伤生物标志物 GFAP 和神经丝轻链（NfL）与接受抗 CD19 CAR-T 细胞治疗的成人患者神经毒性和内皮功能障碍相关

Chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19 have revolutionized the treatment of B-cell malignancies, but their use is frequently complicated by immune effector cell-associated neurotoxicity syndrome (ICANS).

The underlying mechanisms include endothelial dysfunction, blood brain barrier disruption, and neuroinflammation. Circulating biomarkers of neuronal and astroglial injury, such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), may provide insight into ICANS pathophysiology and serve as predictive tools.

We conducted a retrospective study of 34 adult patients treated with anti-CD19 CAR-T cells for B-cell malignancies. Serum NfL and GFAP were measured at infusion (day 0) and day 7 using ultrasensitive immunoassays. Baseline GFAP and NfL levels correlated with endothelial activation markers, including mEASIX and lactate dehydrogenase, but not with demographic variables. ICANS of any grade occurred in 34% of patients, and baseline levels of both GFAP and NfL were significantly associated with ICANS development and with steroid requirement.

In contrast, changes in biomarker concentrations between day 0 and day 7 were not statistically significant overall, although individual variability was observed. At day 7, elevated NfL levels correlated with laboratory evidence of disseminated intravascular coagulation (DIC), prolonged clotting time, and C-reactive protein elevation.

GFAP elevation was also linked to coagulopathy, particularly prolonged clotting time. Baseline serum levels of GFAP and NfL predict the risk of ICANS and the need for corticosteroid intervention in CAR-T-treated adults, supporting their role as biomarkers of pre-existing neuronal susceptibility.

Furthermore, their association with coagulation abnormalities underscores the interplay between neurotoxicity, endothelial stress, and systemic inflammation.

These findings highlight the potential clinical utility of integrating GFAP and NfL into multimodal biomarker panels to improve risk stratification and management of CAR-T neurotoxicity.