Prognostic significance of vascular endothelial growth factor and circulating endothelial cells for early and late outcomes of allogeneic hematopoietic stem cell transplantation

Аннотация

A number of studies evaluated predictive value of endothelial damage markers on outcomes of allogeneic hematopoietic stem cell transplantation (alloHSCT), but they were rarely measured in combination and with long follow up. In this study we evaluated predictive value of vascular endothelial growth factor (VEGF) and circulating endothelial cells (CEC) on early and late non-relapse mortality (NRM). Given the known negative prognostic impact of VEGF expression in hematologic malignancies undergoing chemotherapy, the second goal was to access impact of VEGF level on relapse incidence after alloHSCT. Level of VEGF was analyzed in 91 consecutive patients before the start of conditioning, on day 0 and on the day of engraftment. CEC were measured in 55 consecutive patients from the same study group at the same time points. Both VEGF and CEC were predicted early, but not late NRM. High level of VEGF on day 0 in multivariate analysis was associated with increased 1-year NRM (55% vs 22%, HR 3.15, 95%CI 1.34-7.40, p=0.009), while high level of CEC before conditioning was associated with increased 1-year NRM in univariate (69% vs 20%, p=0.001), but not multivariate analysis (95%CI 0.84-5.76, p=0.102). High VEGF A level before conditioning was associated with increased 1-year relapse rate (55% vs 22%, p=0.001, HR 3.15, 95%CI 1.34-7.40), but had no impact on late relapses and 3-year overall survival (50% vs 42% respectively, p=0.60), as a large proportion of patients were successfully salvaged after relapse. CEC were not a significant prognostic factor for relapse (p=0.09). No correlation was found between VEGF and CEC at any time point (p>0.05), indicating that they may represent different aspects of endothelial dysfunction. In conclusion, VEGF and CEC are valuable biomarkers to predict early NRM, and VEGF is also a predictive factor of early relapse after alloHSCT.