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Blood, 8 January 2009, Vol. 113, No. 2, pp. 273-278. Prepublished online as a Blood First Edition Paper on October 2, 2008; DOI 10.1182/blood-2008-07-167098.
PLENARY PAPER A biomarker panel for acute graft-versus-host disease1 Department of Pediatrics, University of Michigan, Ann Arbor; 2 Fred Hutchinson Cancer Research Center, Seattle, WA; 3 Department of Internal Medicine, 4 Department of Biostatistics, 5 Comprehensive Cancer Center Biostatistics Core, and 6 Department of Surgery, University of Michigan, Ann Arbor; and 7 Department of Pediatrics, Case Western Reserve University, Cleveland, OH
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.
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