Weissinger, E. M. and Metzger, J. and Dobbelstein, C. and Wolff, D. and Schleuning, M. and Kuzmina, Z. and Greinix, H. and Dickinson, A. M. and Mullen, W. and Kreipe, H. and Hamwi, I. and Morgan, M. and Krons, A. and Tchebotarenko, I. and Ihlenburg-Schwarz, D. and Dammann, E. and Collin, M. and Ehrlich, S. and Diedrich, H. and Stadler, M. and Eder, M. and Holler, E. and Mischak, H. and Krauter, J. and Ganser, A. (2014) Proteomic peptide profiling for preemptive diagnosis of acute graft-versus-host disease after allogeneic stem cell transplantation. LEUKEMIA, 28 (4). pp. 842-852. ISSN 0887-6924, 1476-5551
Full text not available from this repository. (Request a copy)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 peptidesderived from albumin, beta 2-microglobulin, CD99, fibronectin and various collagen alpha-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | UNRELATED DONORS; APLASTIC-ANEMIA; MASS-SPECTROMETRY; RISK-FACTORS; ACUTE GVHD; FOLLOW-UP; BIOMARKERS; THERAPY; GLOBULIN; ALBUMIN; hematopoietic stem cell transplantation; graft-versus-host disease; proteomics; capillary electrophoresis; mass spectrometry |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Nov 2019 09:03 |
| Last Modified: | 15 Nov 2019 09:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10374 |
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