Article

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

Department of Pediatrics, University of Michigan, Ann Arbor, USA.
Blood (impact factor: 9.9). 11/2008; 113(2):273-8. DOI:10.1182/blood-2008-07-167098 pp.273-8
Source: PubMed

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.

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    Article: Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation.
    E Holler, H J Kolb, A Möller, J Kempeni, S Liesenfeld, H Pechumer, W Lehmacher, G Ruckdeschel, B Gleixner, C Riedner
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    ABSTRACT: Acute graft-versus-host disease, interstitial pneumonitis, endothelial leakage syndrome, and veno-occlusive disease are major complications of bone marrow transplantation. Though several new regimens for prophylaxis and treatment of these syndromes have been introduced, the overall incidence has been only slightly reduced over the last few years. We retrospectively analyzed tumor necrosis factor alpha (TNF alpha) serum levels between day -8 and day 100 after bone marrow transplantation in 56 patients transplanted in our unit for a variety of hematological diseases. In 34 patients with uneventful courses, mean TNF alpha levels rose to a maximum of 76 +/- 29 pg/mL. In contrast, 22 patients with major transplant related complications showed mean increases of TNF alpha of 492 +/- 235 pg/mL (P less than .0001). Increases of TNF alpha occurred before interstitial pneumonitis and severe acute graft-versus-host disease with a latency of 25 to 54 days. Early complications such as endothelial leakage syndrome and veno-occlusive disease were closely associated with increases of TNF alpha serum levels. Our study suggests two pathways of TNF alpha release: activation of host macrophages and stimulation of donor cells in the course of acute graft-versus-host disease. Cytokine monitoring should be helpful for prediction and earlier treatment of major transplant related complications.
    Blood 03/1990; 75(4):1011-6. · 9.90 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

2 groups
 
4 biomarkers
 
4 proteins
 
42 patients
 
8 proteins
 
95% confidence interval
 
acute graft-versus-host disease
 
antibody microarrays
 
biomarker panel
 
characteristic curve distinguishing
 
clinical symptoms
 
composite biomarker panel
 
Cox regression analysis
 
enzyme-linked immunosorbent assay
 
hepatocyte growth factor
 
Logistic regression analysis
 
optimally discriminated patients
 
prognostic information independent
 
revealed 8 potential biomarkers
 
validated biomarkers