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

Abstract

The physio-pathologic interrelationships between endothelium and GvHD have been better elucidated and have led to definition of the entity 'endothelial GvHD' as an essential early phase prior to the clinical presentation of acute GvHD. Using the CellSearch system, we analyzed circulating endothelial cells (CEC) in 90 allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients at the following time-points: T1 (pre-conditioning), T2 (pre-transplant), T3 (engraftment), T4 (onset of GvHD) and T5 (1 week after steroid treatment). Although CEC changes in allo-HSCT represent a dynamic phenomenon influenced by many variables (that is, conditioning, immunosuppressive treatments, engraftment syndrome and infections), we showed that CEC peaks were constantly seen at onset of acute GvHD and invariably returned to pre-transplant values after treatment response. Since we showed that CEC changes during allo-HSCT has rapid kinetics that may be easily missed if blood samples are drawn at pre-fixed time-points, we rather suggest an 'on demand' evaluation of CEC counts right at onset of GvHD clinical symptoms to possibly help differentiate GvHD from other non-endothelial complications. We confirm that CEC changes are a suitable biomarker to monitor endothelial damage in patients undergoing allo-transplantation and hold the potential to become a useful tool to support GvHD diagnosis (ClinicalTrials.gov NCT02064972).

Endothelial damage and dysfunction in acute graft-versus-host disease

“…This finding is consistent with a previously published study, demonstrating increased endothelial injury in human skin biopsies during aGVHD. 10 Additionally, a series of clinical studies have collected supporting evidence on increased endothelial dysfunction during aGVHD, such as high numbers of circulating ECs [40][41][42][43] and elevated serum levels of the endothelial stress markers ST2, von Willebrand factor, angiopoietin 2 and thrombomodulin. 31,[44][45][46] We have previously shown that aGVHD is associated to increased angiogenesis in target organs.…”

Endothelial injury and thrombotic microangiopathy in COVID-19: Treatment with the lectin-pathway inhibitor narsoplimab

“…To reduce operator-induced variability, all samples were analyzed by the same laboratory technician. CEC values were calculated by a dual-platform counting method using the lymphocyte subset as reference population as previously reported ( Almici et al, 2017 ).…”

Prognostic plasma biomarkers of early complications and graft‐versus‐host disease in patients undergoing allogeneic hematopoietic stem cell transplantation

“…Biomarkers could be either: (a) diagnostic biomarker (that identifies patients at the onset of clinical disease); (b) prognostic (that identifies the likelihood of a clinical event occurrence in HCT recipients), or (c) predictive (that categorizes patients by their likelihood of response to a particular treatment when measured prior to the treatment) [2]. Since GVHD and RRTs share a common trigger, particularly damaged endothelium [5], circulating endothelial cells (CECs) have been evaluated as a diagnostic biomarker for SOS [6] and as a prognostic marker for endothelial damage [7–10], acute GVHD [7,11], and thrombotic microangiopathy (TMA) [12]. Similarly, regulatory T cells (Tregs) [13], CD146 + T cells [14] and invariant natural killer T cells [15] have been evaluated as diagnostic/prognostic biomarkers for acute GVHD.…”