{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:01:06Z","timestamp":1781632866502,"version":"3.54.5"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013brain 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.<\/jats:p>","DOI":"10.1007\/s10238-026-02051-4","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:43:21Z","timestamp":1768805001000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neuronal injury biomarkers GFAP and neurofilament light chains (NfL) are associated with neurotoxicity and endothelial dysfunction in adult patients treated with antiCD19 CART cells"],"prefix":"10.1007","volume":"26","author":[{"given":"Eugenio","family":"Galli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Modoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Battistini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisella","family":"Guerrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Pansini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Corrente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hohaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Chiusolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Sor\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Calabresi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Sica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"issue":"6","key":"2051_CR1","first-page":"294","volume":"28","author":"SJ Grant","year":"2022","unstructured":"Grant SJ, Grimshaw AA, Silberstein J, Murdaugh D, Wildes TM, Rosko AE, et al. Clinical Presentation, risk Factors, and outcomes of immune effector cell-Associated neurotoxicity syndrome following chimeric antigen receptor T cell therapy: A systematic review. Transpl Cell Ther [Internet]. 2022;28(6):294\u2013302.","journal-title":"Transpl Cell Ther [Internet]"},{"issue":"1","key":"2051_CR2","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41571-022-00704-3","volume":"20","author":"CL Flugel","year":"2023","unstructured":"Flugel CL, Majzner RG, Krenciute G, Dotti G, Riddell SR, Wagner DL, et al. Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours. Nat Rev Clin Oncol [Internet]. 2023;20(1):49\u201362.","journal-title":"Nat Rev Clin Oncol [Internet]"},{"issue":"1","key":"2051_CR3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrclinonc.2017.148","volume":"15","author":"SS Neelapu","year":"2018","unstructured":"Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol [Internet]. 2018;15(1):47\u201362.","journal-title":"Nat Rev Clin Oncol [Internet]"},{"key":"2051_CR4","doi-asserted-by":"crossref","unstructured":"Siegler EL, Kenderian SS. Neurotoxicity and cytokine release syndrome after chimeric antigen receptor T cell therapy: insights into mechanisms and novel therapies. Front Immunol [Internet]. 2020;11.","DOI":"10.3389\/fimmu.2020.01973"},{"issue":"6","key":"2051_CR5","doi-asserted-by":"publisher","first-page":"3129","DOI":"10.1007\/s00277-025-06467-y","volume":"104","author":"X Wang","year":"2025","unstructured":"Wang X, He X, Zhang T, Liu J, Zhao M. Latest updates on pathogenesis mechanisms and management strategies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis related to CAR-T cell therapies. 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Blood Adv [Internet]. 2023 Mar;28(6):1001\u201310.","DOI":"10.1182\/bloodadvances.2022008119"}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-026-02051-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-026-02051-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-026-02051-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:48:49Z","timestamp":1781632129000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-026-02051-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,19]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2051"],"URL":"https:\/\/doi.org\/10.1007\/s10238-026-02051-4","relation":{},"ISSN":["1591-9528"],"issn-type":[{"value":"1591-9528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,19]]},"assertion":[{"value":"20 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients included in the study consented to participate and to anonymous use and publication of their data. A written informed consent was obtained for all patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the local ethics committee (ID 4879, Prot. 0020777\/22, Amendment 09\/2024). All patients included in the study consented to participate and signed in informed consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}],"article-number":"121"}}