A biomarker panel for acute graft-versus-host disease.

Publication Type:

Journal Article

Source:

Blood, Volume 113, Issue 2, p.273-8 (2009)

Keywords:

2009, Acute Disease, Adolescent, Adult, Aged, Biological Markers, Center-Authored Paper, Child, Child, Preschool, Disease-Free Survival, Female, Graft vs Host Disease, hematopoietic stem cell transplantation, Hepatocyte Growth Factor, Humans, Infant, Interleukin-2 Receptor alpha Subunit, Interleukin-8, Male, Middle Aged, Predictive Value of Tests, Public Health Sciences Division, Receptors, Tumor Necrosis Factor, Type I, Retrospective Studies, Survival Rate, Transplantation, Homologous

Abstract:

No validated biomarkers exist for acute graft-versus-host disease (GVHD). We screened plasma with antibody microarrays for 120 proteins in a discovery set of 42 patients who underwent transplantation that revealed 8 potential biomarkers for diagnostic of GVHD. We then measured by enzyme-linked immunosorbent assay (ELISA) the levels of these biomarkers in samples from 424 patients who underwent transplantation randomly divided into training (n = 282) and validation (n = 142) sets. Logistic regression analysis of these 8 proteins determined a composite biomarker panel of 4 proteins (interleukin-2-receptor-alpha, tumor-necrosis-factor-receptor-1, interleukin-8, and hepatocyte growth factor) that optimally discriminated patients with and without GVHD. The area under the receiver operating characteristic curve distinguishing these 2 groups in the training set was 0.91 (95% confidence interval, 0.87-0.94) and 0.86 (95% confidence interval, 0.79-0.92) in the validation set. In patients with GVHD, Cox regression analysis revealed that the biomarker panel predicted survival independently of GVHD severity. A panel of 4 biomarkers can confirm the diagnosis of GVHD in patients at onset of clinical symptoms of GVHD and provide prognostic information independent of GVHD severity.