Biomarkers for Early Complications of Endothelial Origin After Allogeneic Hematopoietic Stem Cell Transplantation: Do They Have a Potential Clinical Role?

Giuseppe Lia,Luisa Giaccone,Sarah Leone,Benedetto Bruno

doi:10.3389/fimmu.2021.641427

Abstract

Endothelial cell (EC) dysfunction causes a number of early and life-threatening post hematopoietic stem cell transplant (HCT) complications that result in a rapid clinical decline. The main early complications are graft-vs.-host disease (GVHD), transplant associated thrombotic microangiopathy (TA-TMA), and sinusoidal obstruction syndrome (SOS). Post-HCT endothelial dysfunction occurs as a result of chemotherapy, infections, and allogeneic reactivity. Despite major advances in transplant immunology and improvements in supportive care medicine, these complications represent a major obstacle for successful HCT. In recent years, different biomarkers have been investigated for early detection of post-transplant endothelial cell dysfunction, but few have been validated. In this review we will define GVHD, TA-TMA and SOS, summarize the current data available in HCT biomarker research and identify promising biomarkers for detection and diagnosis of early HCT complications.

Highlights

Hematopoietic cell transplantation (HCT) is indicated in a broad range of diseases, most frequently acute leukaemia and myelodysplastic syndromes [1]
We describe the current biomarker research and highlight potential biomarkers that could have a potential role in clinical practise
This study showed that there is an increase of sCAMs and PAI-1 level in all patients, confirming that endothelial damage is a common feature in alloHCT, but this increase is statistically significant only in patients not treated with recombinant TM

Summary

INTRODUCTION

Hematopoietic cell transplantation (HCT) is indicated in a broad range of diseases, most frequently acute leukaemia and myelodysplastic syndromes [1]. The first “hit” makes the endothelium more procoagulant This damage occurs in the early post-HCT aplastic phase and is generally caused by conditioning regimen in presence of concurrent risk factors (e.g. prolonged immobilization, severe infections, high dose busulfan) [43]. Soluble adhesion molecules, circulating endothelial cells and endothelial cell progenitors, coagulation factors, pro-inflammatory mediators and hyaluronic acid (HA) are all being actively tested (Table 1) [33, 62, 66, 109, 110], and several studies are investigating their diagnostic, predictive and prognostic values in early post-HCT complications. Additional studies have expanded on these data and discovered changes in soluble protein expression that are specific to patients with post-HCT complications such as SOS, GVHD and TA-TMA. PAI-1 marker performed poorly in proteomic-based approach and it was not included as predictive marker in the final composite biomarker panel [66]

Detection methods

Findings

CONCLUSIONS AND PERSPECTIVES