Preconditioning Serum Levels of Endothelial Cell-Derived Molecules and the Risk of Posttransplant Complications in Patients Treated with Allogeneic Stem Cell Transplantation
Endothelial cells are involved in the pathogenesis of acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. These cells express several molecules that can be detected as biologically active soluble forms; serum levels of these molecules may thereby reflect the functional status of endothelial cells. Furthermore, acute GVHD is an inflammatory reaction and endothelial cells function as local regulators of inflammation. We therefore investigated whether differences in preconditioning/pretransplant serum levels of endothelium-expressed molecules (i.e., endocan, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin) were associated with a risk of posttransplant GVHD. Our study should be regarded as a population-based study of consecutive and thereby unselected patients (). Analysis of this pretreatment endothelium biomarker profile by unsupervised hierarchical clustering identified a subset of patients with increased early nonrelapse mortality. Furthermore, low endocan levels were significantly associated with acute GVHD in the liver and gastrointestinal tract, whereas high VCAM-1 levels were associated with acute GVHD in the skin only. Our study suggests that the preconditioning/pretransplant status of endothelial cells (possibly through altered trafficking of immunocompetent cells) is important for the risk and the organ involvement of later acute GVHD. 1. Introduction Allogeneic hematopoietic stem cell transplantation has a strong antileukemic effect [1, 2] but is also associated with a relatively high risk of serious posttransplant complications, for example, graft-versus-host disease (GVHD) [3]. Endothelial cells and endothelial cell damage seem to be involved in the development of several posttransplant complications, including GVHD [4–6]. Furthermore, endothelial cell adhesion molecules are highly expressed after allotransplantation especially in GVHD-affected tissue, and soluble E-selectin (CD62E) serum levels are increased during acute GVHD whereas levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) are only increased in chronic GVHD [6–8]. Levels of circulating endothelial cells can also be a marker of conditioning-induced endothelial damage [9, 10]. All these observations are consistent with the hypothesis that endothelial cells are important in GVHD development. Finally, endocan is a proteoglycan expressed by endothelial cells; a soluble form is detected in serum [11] and the serum levels can be altered by infections, trauma, and malignancies as well as nonmalignant
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