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

Abstract

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.

Circulating endothelial cell count: a reliable marker of endothelial damage in patients undergoing hematopoietic stem cell transplantation

“…20 Furthermore, the use of standardized criteria for signal intensity and automated image analysis guarantees a better reproducibility by reducing inter-operator variability. 20 As we previously reported, 19 we further confirmed, on a larger patient series, that statistically significant higher CEC counts (P o 0.003) are seen at engraftment in patients with no GvHD vs those who develop GvHD. This puzzling finding may also be correlated with the decreased CEC counts associated with higher GvHD grades we documented, although with the limitation of the low number of GvHD grade III patients and the lack of GvHD grade IV patients in our series.…”

“…However, their encouraging findings need to be confirmed in larger studies to establish the real role of CEC as a biomarker of endothelial damage. 29 Not only does our study confirm a preliminary report 19 but it also represents the largest series of allo-HSCT patients where the clinical usefulness of CEC changes over time has prospectively been correlated to the diagnosis of GvHD and treatment response. Although CEC changes in allo-HSCT represent a dynamic phenomenon that can be influenced by many variables (among others, conditionings, immunosuppressive treatments, engraftment syndrome, infections), we clearly showed that CEC peaks were constantly seen prior to the onset of acute GvHD and invariably returned to pre-transplant values after treatment response.…”

“…CEC are considered specific and sensitive markers of endothelial dysfunction and have been used in a variety of pathological conditions to monitor vascular damage. 12,[16][17][18][19]28 The commercial availability of the CellSearch system for CEC identification and count allows to easily monitor CEC changes as a function of endothelial damage in allo-HSCT patients. 19 Since validated noninvasive biomarkers for GvHD diagnosis have not yet routinely been implemented in clinical practice, 14 we propose the CellSearch system as a valid and reliable approach to help/support clinicians in their diagnosis of acute GvHD.…”

“…15 In recent years, the direct count of circulating endothelial cells (CEC) has emerged as a valuable biomarker of endothelial damage in a variety of disorders. 8,12,[16][17][18][19][20] However, due to their very low numbers and complex phenotype, several published techniques have shown different degrees of variability, reporting a wide range of CEC values (0-7900 CEC/mL) in healthy subjects. 12,[21][22][23][24] We prospectively correlated CEC count changes to GvHD onset and response to treatment in 90 allo-HSCT patients.…”

A risk-adapted approach to acute GVHD treatment: are we there yet?

“…Both of these strategies hold value in identifying HR patients, but neither take into account the endothelium, a key target of aGVHD associated with a poor prognosis. 6,[10][11][12] In addition, both of these strategies are based upon the extent of inflammation and tissue damage at presentation. Neither strategy considers the patient's capacity to heal damaged tissues, which recent data indicate may be a critical factor for response to therapy and potentially may explain discrepancies between assigned aGVHD risk and outcome.…”