Plasma-derived proteomic biomarkers in human leukocyte antigen-haploidentical or human leukocyte antigen-matched bone marrow transplantation using post-transplantation cyclophosphamide

Christopher G. Kanakry, Giorgos Bakoyannis, Susan Perkins, Shannon R. McCurdy, Ante Vulic, Edus H. Warren, Etienne Daguindau, Taylor Olmsted, Christen Mumaw, Andrea M.H. Towlerton, Kenneth R. Cooke, Paul V. O’Donnell, Heather J. Symons, Sophie Paczesny, Leo Luznik

Research output: Contribution to journalArticle

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Abstract

Recent 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 cyclophos-phamide-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.

Original languageEnglish (US)
Pages (from-to)932-940
Number of pages9
JournalHaematologica
Volume102
Issue number5
DOIs
StatePublished - Apr 30 2017

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HLA Antigens
Bone Marrow Transplantation
Proteomics
Cyclophosphamide
Transplantation
Biomarkers
Graft vs Host Disease
Mortality
Blood Proteins
Interleukin-2 Receptors
Bone Marrow
Transplants
Tumor Necrosis Factor Receptors
Area Under Curve
Enzyme-Linked Immunosorbent Assay
Prospective Studies
T-Lymphocytes
Serum
Genes
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Plasma-derived proteomic biomarkers in human leukocyte antigen-haploidentical or human leukocyte antigen-matched bone marrow transplantation using post-transplantation cyclophosphamide. / Kanakry, Christopher G.; Bakoyannis, Giorgos; Perkins, Susan; McCurdy, Shannon R.; Vulic, Ante; Warren, Edus H.; Daguindau, Etienne; Olmsted, Taylor; Mumaw, Christen; Towlerton, Andrea M.H.; Cooke, Kenneth R.; O’Donnell, Paul V.; Symons, Heather J.; Paczesny, Sophie; Luznik, Leo.

In: Haematologica, Vol. 102, No. 5, 30.04.2017, p. 932-940.

Research output: Contribution to journalArticle

Kanakry, CG, Bakoyannis, G, Perkins, S, McCurdy, SR, Vulic, A, Warren, EH, Daguindau, E, Olmsted, T, Mumaw, C, Towlerton, AMH, Cooke, KR, O’Donnell, PV, Symons, HJ, Paczesny, S & 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, vol. 102, no. 5, pp. 932-940. https://doi.org/10.3324/haematol.2016.152322
Kanakry, Christopher G. ; Bakoyannis, Giorgos ; Perkins, Susan ; McCurdy, Shannon R. ; Vulic, Ante ; Warren, Edus H. ; Daguindau, Etienne ; Olmsted, Taylor ; Mumaw, Christen ; Towlerton, Andrea M.H. ; Cooke, Kenneth R. ; O’Donnell, Paul V. ; Symons, Heather J. ; Paczesny, Sophie ; Luznik, Leo. / Plasma-derived proteomic biomarkers in human leukocyte antigen-haploidentical or human leukocyte antigen-matched bone marrow transplantation using post-transplantation cyclophosphamide. In: Haematologica. 2017 ; Vol. 102, No. 5. pp. 932-940.
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