Biomarkers in chronic graft-versus-host disease: quo vadis?

Wolff, D. and Greinix, H. and Lee, S. J. and Gooley, T. and Paczesny, S. and Pavletic, S. and Hakim, F. and Malard, F. and Jagasia, M. and Lawitschka, A. and Hansen, J. A. and Pulanić, Dražen and Holler, E. and Dickinson, A. and Weissinger, E. and Edinger, M. and Sarantopoulos, S. and Schultz, K. R. (2018) Biomarkers in chronic graft-versus-host disease: quo vadis? Bone Marrow Transplantation, 53 (7). pp. 832-837. ISSN 0268-3369

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Abstract

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.

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