Changes in Circulating Endothelial Cells Count Could Become a Valuable Tool in the Diagnostic Definition of Acute Graft-Versus-Host Disease

Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is burdened by life-threatening complications, with graft-versus-host disease (GvHD) being the major cause of morbility and mortality. Recently, clinical and physiopathologic evidences showed that vascular endothelium can be a target of GvHD in the early phase and circulating endothelial cells (CECs) represent surrogate markers of endothelial damage. Methods. Using the CellSearch System (Veridex LLC, Raritan, NJ), CECs were counted before (T1), after conditioning regimen (T2), at engraftment (T3), at GvHD onset (T4), and after steroid treatment (T5) in 40 patients (7 Hodgkin's Disease, 13 Acute Myeloblastic Leukemia, 5 Acute Lymphoblastic Leukemia, 8 Multiple Myeloma, 3 Chronic Lymphocytic Leukemia, 1 Non-Hodgkin Lymphoma, 1 Chronic Myeloid Leukemia, 2 Severe Aplastic Anemia) undergoing allo-HSCT. Results. The median CEC per milliliter at T1 was 20 (n=33, range 4-718), in comparison to a value of 2 (range, 1-14) in controls (P<0.001). At T3, CEC per milliliter were 47 (range, 16-148) in GvHD patients and 92 (range, 23-276) in patients without GvHD (P=0.006). This difference remained significant in multivariate analysis (odds ratio, 0.97; 95% confidence interval, 0.96-0.99; P=0.02). At GvHD onset, the relative increase of CEC counts from time of engraftment (T4 vs. T3) was 44% (range, -43% to 569%) in GvHD patients versus 0% (range, -49% to 2%) in patients without GvHD (P=0.003), being confirmed as significant in multivariate analysis (odds ratio, 1.04; 95% confidence interval, 1.0-1.08; P=0.04). Conclusion. Changes in CEC count can represent a promising marker to monitor endothelial damage in patients undergoing allo-HSCT and could become a valuable tool in the diagnostic definition of GvHD.