Comprehensive assessment of endothelial dysfunction before cellular therapy: EASIX, local imaging, and systemic...

Endothelial dysfunction contributes to mortality after cellular therapies, yet its clinical assessment remains challenging. In this prospective observational study, we evaluated 169 patients undergoing allogeneic stem cell transplantation or chimeric antigen receptor T-cell therapy and 102 healthy controls to determine whether a comprehensive endothelial profile, including the endothelial activation and stress index (EASIX), glycocalyx thickness (via sublingual GlycoCheck microscopy), digital perfusion (Tivita hyperspectral imaging), endothelial serum markers (angiopoietin-2, soluble thrombomodulin [CD141], chemokine (C-X-C motif) ligand 8, chemokine (C-X-C motif) ligand 9, interleukin-18, enzyme-linked immunosorbent assays), and platelet aggregation (flow cytometry), correlates with clinical outcomes. We observed significant intercorrelations among EASIX, perfused boundary region (PBR), tissue perfusion, and endothelial serum markers. Importantly, elevated EASIX, angiopoietin-2, impaired PBR, and reduced digital perfusion were significantly associated with early sepsis, whereas EASIX also independently predicted nonrelapse mortality. These findings highlight the heterogeneity of endothelial responses to systemic insult and reinforce the need for multimodal assessment in a larger study. EASIX, as a simple and routinely available marker, emerges as a valuable tool to stratify endothelial risk and guide monitoring in patients undergoing cellular therapy. This trial was registered at www.ClinicalTrials.gov as #NCT05502887.