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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.

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


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.

[Indexed for MEDLINE]

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