Endothelial Dysfunction and Risk of Acute Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation: END-GAME Prospective Study Final Results

• Published in: Blood 2024-11, Vol.144, p.3520-3520
• Main Authors: Bianchessi, Antonio, Defrancesco, Irene, Ferretti, Virginia Valeria, Picone, Cristina, Ferrari, Beatrice, Zerbi, Caterina, Romano, Francesco, Losi, Giulia, Consensi, Erica, De Amici, Mara, Testa, Giorgia, Zoboli, Valentina, Taurino, Alessia, Colombo, Anna Amelia, Arcaini, Luca, Polverelli, Nicola
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-208075

Background. Endothelial dysfunction has been increasingly correlated to the very early phases of acute graft-versus-host-disease (aGVHD) with endothelial cells acting both as starting elements of the inflammatory process and as a target of alloreactive donor T cells (“endothelial GVHD”). Aim and Methods. This observational prospective single-center study investigates the role of endothelial dysfunction at the time of allogeneic hematopoietic stem cell transplantation (HSCT) in predicting the incidence of aGVHD. Inclusion criteria were: adult patients (≥18 years old) undergoing their first HSCT for any hematological disease, from any donor and any stem cell source. The primary endpoint was cumulative incidence of aGVHD at day 100 post-HSCT. Levels of circulating endothelial cells (CECs), circulating endothelial progenitors (CEPs) and some soluble biomarkers (plasminogen activator inhibitor-1 [PAI-1], vascular endothelial growth factor [VEGF-A], angiopoietin-2 [ANG-2], soluble VCAM [sVCAM-1]) were assessed on peripheral blood samples collected on the day of HSCT (T0). CECs and CEPs were identified by flow cytometry according to Lanuti et al. 2018 and Mancuso et al. 2020 protocol, respectively. CECs >30 cells/ml were considered elevated. Since a normal reference range for CEPs has not yet been established, they were divided into tertiles. Soluble biomarkers were analyzed using the automated microfluidic analyzer ELLA (BioTechne, Minneapolis, USA), according to the manufacturer's protocol and results expressed by pg/ml. Statistical analysis was performed in accordance with the EBMT recommendations. As this is a proof-of-concept study, p-values