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Leukemia. 2014 Apr;28(4):842-52. doi: 10.1038/leu.2013.210. Epub 2013 Jul 11.

Proteomic peptide profiling for preemptive diagnosis of acute graft-versus-host disease after allogeneic stem cell transplantation.

Author information

1
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
2
Mosaiques Diagnostics GmbH, Hannover, Germany.
3
Deptartment of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
4
Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
5
Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
6
Department of Hematology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
7
Biomarkers and Systems Medicine group, University of Glasgow, Glasgow, UK.
8
Department of Pathology, Hannover Medical School, Hannover, Germany.
9
Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.

Abstract

Allogeneic hematopoietic stem cell transplantation is one curative treatment for hematological malignancies, but is compromised by life-threatening complications, such as severe acute graft-versus-host disease (aGvHD). Prediction of severe aGvHD as early as possible is crucial to allow timely initiation of treatment. Here we report on a multicentre validation of an aGvHD-specific urinary proteomic classifier (aGvHD_MS17) in 423 patients. Samples (n=1106) were collected prospectively between day +7 and day +130 and analyzed using capillary electrophoresis coupled on-line to mass spectrometry. Integration of aGvHD_MS17 analysis with demographic and clinical variables using a logistic regression model led to correct classification of patients developing severe aGvHD 14 days before any clinical signs with 82.4% sensitivity and 77.3% specificity. Multivariate regression analysis showed that aGvHD_MS17 positivity was the only strong predictor for aGvHD grade III or IV (P<0.0001). The classifier consists of 17 peptides derived from albumin, β2-microglobulin, CD99, fibronectin and various collagen α-chains, indicating inflammation, activation of T cells and changes in the extracellular matrix as early signs of GvHD-induced organ damage. This study is currently the largest demonstration of accurate and investigator-independent prediction of patients at risk for severe aGvHD, thus allowing preemptive therapy based on proteomic profiling.

PMID:
23842427
DOI:
10.1038/leu.2013.210
[Indexed for MEDLINE]

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