A Novel Diagnostic and Prognostic Biomarker Panel for Endothelial Cell Damage-Related Complications in Allogeneic...

Noninfectious transplantation-related complications (TRCs), such as graft-versus-host disease or TRC with endothelial cell damage (TRC-EC), remain as the major obstacle for successful allogeneic hematopoietic cell transplantation (allo-HCT). However, the diagnosis and prognosis for the emergence of these complications are difficult to define during the early post allo-HCT period. Here, we tried to generate a novel diagnostic system for TRC-EC by analyzing 188 adult patients who received allo-HCT. Our study found that the peripheral blood levels of angiopoietin 2 (ANG2), C-reactive protein (CRP), D-dimer, and thrombomodulin (TM) at the onset of TRCs were significantly associated with the development of TRC-EC. We next developed a composite biomarker panel incorporating the risk values of ANG2, CRP, D-dimer, and TM at the onset of TRCs, which classified these patients into 3 risk groups: low, intermediate, and high risk. As a result, the panel was useful not only for the diagnosis of TRC-EC with high specificity and sensitivity, but also for the prediction of the patients' long-term outcome. The 5-year overall survival (OS) rates of patients in the low-, intermediate-, and high-risk groups since the occurrence from TRCs were 76.2%, 54.9%, and 26.9%, respectively, and the high-risk score was significantly associated with both poor OS (hazard ratio [HR], 5.60; 95% confidence interval [CI], 2.81 to 11.20; P < .01) and frequent nonrelapse mortality (HR, 19.75; 95% CI, 5.59 to 69.77; P < .01). Thus, the composite panel proposed in this study provides a powerful tool for the diagnosis of TRC-EC and for the prediction of survival for patients with TRC-EC after allo-HCT.