Endothelial Dysfunction in Autologous Hematopoietic Stem Cell Transplantation.

Introduction: Intensive conditioning regimen and allo-reactivity seem to be the main causes of the endothelial dysfunction observed after allogeneic HSCT. This dysfunction may be the origin of some early complications after HSCT. To evaluate if a less intensive conditioning without allo-reactivity phenomena produces endothelial dysfunction we analyzed a group of patients receiving autologous HSCT.

Methods: Blood samples were collected from patients (n=10) before receiving BEAM treatment (pre), and at days 0, 7, 14 and 21 after the HSCT. Soluble markers of endothelial damage (von Willebrand Factor [VWF], sE-selectin, sVCAM1, sICAM1, TNFalphaRI and II, MMP9) were measured in plasma samples by ELISA. Expression of the adhesion receptors E-selectin, VCAM1 and ICAM1, on endothelial cells (EC) cultured in the presence of a pool of sera, obtained at the different time points during the BEAM treatment, was analyzed by immunocytochemistry. Changes in the expression of VWF in the extracellular matrix generated by these EC were evaluated by using the same technique. Leukocyte adhesion on EC monolayers under flow conditions was also studied. The effect on cell cycle and apoptosis was also explored.

Results: Plasma levels of VWF and sICAM1 increased progressively after the HSCT, peaking on day 14 (84% and 118%, respectively, vs pre; p<0.01), although no increments were detected for sVCAM1 and sE-selectin. TNFalphaRI and RII increased from 0 (pre value) to 5, 12, respectively, and MMP9 from 0 (value at day 7) to 300ng/ml. Exposure of cultured EC to patients sera caused an increased expression of all adhesion receptors studied on the EC surface and of VWF on their extracellular matrix, more notable at day 14 and specially for VCAM1. Leukocyte adhesion on EC cultured with sera from day 14 showed a 6-fold rise compared to controls. Although no signs of apoptosis were detected, cell growth was accelerated at day 14.

Conclusions: The increases in the markers of endothelial inflammation detected both in the ex vivo and in the in vitro approaches suggest that there is endothelial damage associated with autologous HSCT. This damage seems to be more important at day 14 after HSCT. A better understanding of the mechanisms involved deserves further investigation.