Endothelial mediators and association with chronic graft-versus-host disease in allogeneic hematopoietic stem cell transplantation: a retrospective single-center study.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for hematological malignancies. However, it is often complicated by chronic graft-versus-host disease (cGVHD), a leading cause of late non-relapse morbidity and mortality. Early identification of patients at risk is therefore critical, yet reliable biomarkers are still lacking. In this study, we evaluated serum endothelial mediator profiles collected 1 year after allo-HSCT and their association with subsequent cGVHD development. Serum samples taken 1 year post-transplant from 82 transplanted patients, of whom 61% developed cGVHD, were analyzed for 19 mediators using Luminex and ELISA assays. Associations between mediator levels and cGVHD were assessed using statistical analysis, logistic regression, and hierarchical clustering. Six mediators, endocan, EMMPRIN, VCAM-1, MMP-1, MMP-8, and MMP-9; differed significantly between patients with and without cGVHD (P < 0.05). Endocan and VCAM-1 remained independently associated with cGVHD in multivariable regression adjusted for age, body mass index (BMI), and prior acute GVHD (aGVHD). Cluster analysis based on these mediators identified distinct patient subgroups. Clusters with generally lower mediator levels had fewer cases of cGVHD, whereas a central cluster with elevated levels showed a higher disease prevalence. Integration of clinical variables confirmed known risk factors, including older age, higher BMI, and previous aGVHD. The identified mediators are biologically linked to endothelial activation and extracellular matrix remodeling. This study is the first to demonstrate that a distinct endothelial- and matrix-remodeling-related serum mediator signature measured 1 year after allo-HSCT is associated with cGVHD. The identified patient clusters provide insight into disease biology and highlight potential biological markers of the disease. These findings support further prospective studies combining longitudinal mediator profiling with clinical data and advanced modeling to improve risk stratification and identify therapeutic targets for the prevention and treatment of cGVHD.