The significance of serum urokinase plasminogen activation receptor (suPAR) in the diagnosis and follow-up of febrile neutropenic patients with hematologic malignancies

Abstract

The purpose of this study was to investigate serum levels of serum urokinase plasminogen activation receptor (suPAR) during the first week of febrile neutropenia and to demonstrate the significance of this biomarker in the diagnosis and follow-up of febrile neutropenic patients with hematologic malignancies. The study was performed between January 2011 and January 2012 at Karadeniz Technical University, Turkey. For neutropenic patients with hematologic malignancies, the day before the onset of fever and the first day of the febrile neutropenia attack were taken as days 0 and 1, respectively. Blood samples were obtained from patients with hematologic malignancies on days 0, 1, 3, 5, and 7. Sixty-eight healthy volunteers were enrolled as the control group. suPAR levels were determined using an ELISA kit following the manufacturer's protocols. Twenty-six male and 14 female patients with hematologic malignancies, the majority with acute/myeloid/lymphocytic leukemia, aged 19-78 years (mean 46.8 years), were included. Fifty febrile neutropenic attacks were investigated in these patients. The mean serum levels of the controls and suPAR 0 were 3.9 ± 1.5 ng/ml and 5.8 ± 2.7 ng/ml, respectively. Serum levels of suPAR rose earlier than levels of C-reactive protein and procalcitonin. Serum suPAR levels increased in patients with hematologic malignancies and were found to represent an important serum biomarker for the early prediction of neutropenic fever. A decrease in serum suPAR levels was found to be correlated with treatment response due to antibiotics in this patient group. There were significant differences in suPAR 1 levels between patients with documented infection and those with fever of unknown origin in favor of the former. When the suPAR 1 results were analyzed using the receiver operating characteristics (ROC) curve method, the optimum diagnostic cut-off point was 5.87 ng/ml, the area underneath the ROC curve (AUC) was 0.81 (95% confidence interval 0.68-0.91), sensitivity was 100%, specificity was 69%, negative predictive value (NPV) was 100%, and positive predictive value (PPV) was 70%. We conclude that suPAR is an important biomarker that can predict infections in the early stage of febrile neutropenia with high sensitivity and NPV for patients with hematologic malignancies. It is also advantageous since it shows the response to treatment with antibiotherapy in the early stage.