{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:37:32Z","timestamp":1792517852297,"version":"4.5.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) are life-threatening complications that often arise after CAR T-cell immunotherapy. Endothelial dysfunction is believed to play a central role in their development, leading to the interest in biomarker-based tools for diagnosis and differentiating these toxicities from sepsis. This study aimed to evaluate the Endothelial Activation Stress Index (EASIX) and its modified version (m-EASIX, which replaces creatinine with C-reactive protein [CRP] (mg\/dL)) as early predictors of severe CRS and ICANS, as well as tools to distinguish CRS from sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>One hundred and nineteen patients treated with CAR T-cell therapy for CD19-positive hematologic malignancies (n=94) or multiple myeloma (n=23) were included. EASIX and m-EASIX scores were measured at various time points: before CAR T-cell infusion, 24\u201348 hours post-infusion, at CRS or ICANS onset, and after treatment for each toxicity. A comparator group of 129 sepsis patients, including 86 with hematologic malignancies, was also analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both EASIX and m-EASIX correlated with biomarkers of endotheliopathy, with m-EASIX showing stronger predictive power for severe toxicities and ICU admission. Higher EASIX and m-EASIX values at early time points were associated with worse overall survival (OS). Furthermore, m-EASIX accurately distinguished CRS from sepsis at symptom onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>m-EASIX is a practical and accessible tool for the early prediction of severe CAR T-cell-related toxicities, risk stratification, and differential diagnosis from sepsis, offering potential to guide clinical decision-making and early intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1664788","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:48:16Z","timestamp":1767768496000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["m-EASIX (better than EASIX) predicts severe CAR T-cell toxicities, worse overall survival, and discriminates cytokine release syndrome from 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