Endothelial Cell Markers Kinetics Following Umbilical Cord Blood Transplantation in Adults.
Authors: Petropoulou Anna D. , Elalamy Ismail , Soria Jeannette , Mirshahi Pezhman , Rendu Francine , Samama Michel Meyer , Marie Jean Pierre , Rio Bernard 
Published: October 2019

Abstract
In organ transplant, alloreactivity is supposed to induce modifications on the vascular endothelium. Complications occurring in the course of allogeneic haematopoietic stem cell (HSC) transplantation, such as acute or chronic graft-versus-host disease (GVHD), have been related to endothelial cell alterations. Moreover, the incidence of GVHD is significantly different following allogeneic bone marrow, peripheral blood stem cell or umbilical cord blood transplantation (BMT, PBSCT and UCBT respectively). Considering these different incidences of acute and chronic GVHD and taking into account the organ transplantation-related vasculopathy, we aimed to further clarify the vascular impact of the three aforementioned sources of HSC. We studied 21 patients (pts), 13 male and 8 female. Mean age was 42 years old (21–64). The underlying diseases were: acute leukaemia (myeloblastic 15pts; lymphoblastic 3pts), multiple myeloma (1pt), aplastic anemia (1pt) and chronic idiopathic myelofibrosis (1pt). Seven pts underwent BMT after myeloablative conditioning regimen (cyclophosphamide and busulphan or 12Gy total body irradiation-TBI), 6 pts PBSCT following non-myeloablative preparative regimen (fludarabine and 2Gy TBI) and 8 pts UCBT after reduced intensity conditioning regimen (cyclophosphamide, fludarabine and 2Gy TBI). We assessed the kinetics of plasma levels of 4 endothelial markers: soluble thrombomodulin (sTM), vWF-Ag, FVIII and the vascular endothelial growth factor (VEGF). Measurements were performed before the conditioning regimen and on days 0, 15, 30, 60, 90. Student paired t-test was used for statistical comparison. Differences were significant if p<0.05. In BMT and PBSCT we observed a significant increase of sTM on days 30 and 60 respectively, in comparison to day 0 (141 ± 42ng/ml and 143 ±13ng/ml respectively, p<0.05). No significant elevation of sTM, compared to pre-conditioning values, was shown in UCBT during the studied period. sTM in UCBT peaked on day 90 (119 ±54ng/ml, p>0.05). Similarly, vWF-Ag was significantly increased on day 0 in BMT and PBSCT (217±66% and 214±93% respectively, p<0.05 compared to pre-conditioning values), whereas in UCBT vWF-Ag levels remained almost unchanged during the studied period. FVIII was significantly elevated on day 15 in PBSCT (200±6%, p<0.05 in comparison to baseline values), but we did not observe any significant increase of FVIII in BMT and UCBT. Finally, there was no significant modification of VEGF in the 3 types of transplantation. Although GVHD was not frequent in this series, the aforementioned results correlated to clinical events. This is one of the first studies investigating the kinetics of different endothelial cell markers following UCBT and comparing them to BMT and PBSCT. A significant difference was observed in the kinetics of endothelial cell markers, according to the source of HSC. Cord blood cells seem to spare vascular endothelium, as shown by the stability of sTM and vWF-Ag plasma levels in the course of the UCBT. The presence of an active phenomenon for induction of tolerance between HSC and vascular wall of inside the cord blood population should be suggested. The low impact of UCBT on the vascular endothelium could possibly be correlated to fewer transplant-related complications and less incidence of GVHD in this type of transplantation.