Biomarkers of Endothelial Damage in Acute Graft‐Versus‐Host Disease After Allogenic Hematopoietic Stem Cell Transplantation: Methodological Challenges

Background Acute graft‐versus‐host disease (aGVHD) is a major complication following allogeneic hematopoietic stem cell transplantation. The current diagnostic approach relies primarily on clinical manifestations and histopathological evaluation of affected tissues. Consequently, there is an urgent need to identify minimally invasive biomarkers that provide predictive, diagnostic, or prognostic value, as well as utility in monitoring therapeutic responses. In particular, biomarkers that enable early identification of patients unresponsive to treatment are highly warranted. Methods This article reviews research on aGVHD biomarkers, with a particular focus on those related to endothelial damage. Data published between 2004 and 2025 were sourced from PubMed, Google Scholar, and ScienceDirect using the following keywords: acute graft versus host disease, endothelial damage, biomarkers, circulating endothelial cells, endothelial progenitor cells, microRNA, extracellular vesicles, serum biomarkers, enzyme‐linked immunosorbent assay, flow cytometry, and analytical errors. This article reviews the findings, with a specific focus on the analytical challenges associated with their determination and the potential for their implementation in clinical settings. Results Recent advances in high‐throughput methodologies have led to the identification of potential biomarkers for aGVHD. Growing evidence indicates that endothelial damage contributes to this complication, especially in treatment‐resistant patients. In addition to soluble serum biomarkers, other promising candidates such as circulating endothelial cells, extracellular vesicles, and microRNAs have been identified. However, the methodologies for their assessment have not yet been standardized. Conclusions Future efforts should focus on standardizing these methods and establishing comprehensive biomarker panels, as none of the biomarkers identified so far are entirely specific to aGVHD.