Browsing by Author "Sarantopoulos, S."

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    B-cell activating factor (BAFF) plasma level at the time of chronic GvHD diagnosis is a potential predictor of non-relapse mortality
    (Nature Publishing Group, 2017-07) Saliba, R.M.; Sarantopoulos, S.; Kitko, C.L.; Pawarode, A.; Goldstein, S.C.; Magenau, J.; Alousi, A.M.; Churay, T.; Justman, H.; Paczesny, Sophie; Reddy, P.; Couriel, D.R.; Pediatrics, School of Medicine
    Biological markers for risk stratification of chronic GvHD (cGvHD) could improve the care of patients undergoing allogeneic hematopoietic stem cell transplantation. Increased plasma levels of B-cell activating factor (BAFF), chemokine (C-X-C motif) ligand 9 (CXCL9) and elafin have been associated with the diagnosis, but not with outcome in patients with cGvHD. We evaluated the association between levels of these soluble proteins, measured by ELISA at the time of cGvHD diagnosis and before the initiation of therapy, with non-relapse-mortality (NRM). Based on the log-transformed values, factor levels were divided into tertiles defined respectively as low, intermediate, and high levels. On univariable analysis, BAFF levels were significantly associated with NRM, whereas CXCL9 and elafin levels were not. Both low (⩽2.3 ng/mL, hazard ratio (HR)=5.8, P=0.03) and high (>5.7 ng/mL, HR=5.4, P=0.03) BAFF levels were associated with a significantly higher NRM compared with intermediate BAFF level. The significant effect of high or low BAFF levels persisted in multivariable analysis. A subset of cGvHD patients had persistently low BAFF levels. In conclusion, our data show that BAFF levels at the time of cGvHD diagnosis are associated with NRM, and also are potentially useful for risk stratification. These results warrant confirmation in larger studies.
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    Biomarkers in chronic graft-versus-host disease: quo vadis?
    (Springer Nature, 2018-07) Wolff, D.; Greinix, H.; Lee, S.J.; Gooley, T.; Paczesny, Sophie; Pavletic, S.; Hakim, F.; Malard, F.; Jagasia, M.; Lawitschka, A.; Hansen, J.A.; Pulanic, D.; Holler, E.; Dickinson, A.; Edinger, M.; Sarantopoulos, S.; Schultz, K. R.; Pediatrics, School of Medicine
    Biomarkers are increasingly used for diagnosis and treatment of transplant-related complications including the first biomarker-driven interventional trials of acute graft-versus-host disease (GvHD). In contrast, the development of biomarkers of chronic GvHD (cGvHD) has lagged behind due to a broader variety of manifestations, overlap with acute GvHD, a greater variation in time to onset and maximum severity, and lack of sufficient patient numbers within prospective trials. An international workshop organized by a North-American and European consortium was held in Marseille in March 2017 with the goal to discuss strategies for future biomarker development to guide cGvHD therapy. As a result of this meeting, two areas were prioritized: the development of prognostic biomarkers for subsequent onset of moderate/severe cGvHD, and in parallel, the development of qualified clinical-grade assays for biomarker quantification. The most promising prognostic serum biomarkers are CXCL9, ST2, matrix metalloproteinase-3, osteopontin, CXCL10, CXCL11, and CD163. Urine-proteomics and cellular subsets (CD4+ T-cell subsets, NK cell subsets, and CD19+CD21low B cells) represent additional potential prognostic biomarkers of cGvHD. A joint effort is required to verify the results of numerous exploratory trials before any of the potential candidates is ready for validation and subsequent clinical application.