https://orcid.org/0000-0001-8125-5723
Key points
Local and systemic test methods highlight the heterogeneity and the systemic nature of human endothelial dysfunction before cell therapy.
Our findings reinforce the utility of EASIX as a clinically practical, endothelial-related biomarker.
Abstract
Endothelial dysfunction contributes to mortality following cellular therapies, yet its clinical assessment remains challenging. In this prospective observational study, we evaluated 169 patients undergoing allogeneic stem cell transplantation (alloSCT) or CAR 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, sCD141, CXCL8, CXCL9, IL-18, ELISAs), 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, while EASIX also independently predicted non-relapse 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. Trial registration: ClinicalTrials.gov NCT05502887
Author notes
Availability of data and materials
Datasets can be accessed upon request.
Acknowledgment
The authors wish to acknowledge the excellent work of Michael Heß (medical research assistant). Samples were processed and provided by NCT Cell and Liquid Biobank, a member of BioMaterialBank Heidelberg.
Funding: No external funding.
