Kanakry, Christopher G.Bakoyannis, GiorgosPerkins, Susan M.McCurdy, Shannon R.Vulic, AnteWarren, Edus H.Daguindau, EtienneOlmsted, TaylorMumaw, ChristenTowlerton, Andrea M.H.Cooke, Kenneth R.O’Donnell, Paul V.Symons, Heather J.Paczesny, SophieLuznik, Leo2017-12-202017-12-202017-05Kanakry, C. G., Bakoyannis, G., Perkins, S. M., McCurdy, S. R., Vulic, A., Warren, E. H., … Luznik, L. (2017). Plasma-derived proteomic biomarkers in human leukocyte antigen-haploidentical or human leukocyte antigen-matched bone marrow transplantation using post-transplantation cyclophosphamide. Haematologica, 102(5), 932–940. http://doi.org/10.3324/haematol.2016.152322https://hdl.handle.net/1805/14848Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor α, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-α all had high areas under the curve of 0.74–0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor α were associated with grade II–IV and III–IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide.en-USAttribution-NonCommercial 3.0 United StatesBiochemical markersProteomicsBone marrow -- TransplantationCyclophosphamideGraft versus host diseaseArticle