Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation

Ayman Akil, Qing Zhang, Christen L. Mumaw, Nisha Raiker, Jeffrey Yu, Nieves Velez de Mendizabal, Laura S. Haneline, Kent A. Robertson, Jodi Skiles, Maribel Diaz-Ricart, Enric Carreras, Jamie Renbarger, Samir Hanash, Robert R. Bies, Sophie Paczesny

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Reliable, noninvasive methods for diagnosing and prognosing sinusoidal obstruction syndrome (SOS) early after hematopoietic cell transplantation (HCT) are needed. We used a quantitative mass spectrometry-based proteomics approach to identify candidate biomarkers of SOS by comparing plasma pooled from 20 patients with and 20 patients without SOS. Of 494 proteins quantified, we selected 6 proteins (L-Ficolin, vascular cell adhesion molecule-1 [VCAM1], tissue inhibitor of metalloproteinase-1, von Willebrand factor, intercellular adhesion molecule-1, and CD97) based on a differential heavy/light isotope ratio of at least 2 fold, information from the literature, and immunoassay availability. Next, we evaluated the diagnostic potential of these 6 proteins and 5 selected from the literature (suppression of tumorigenicity-2 [ST2], angiopoietin-2 (ANG2), hyaluronic acid [HA], thrombomodulin, and plasminogen activator inhibitor-1) in samples from 80 patients. The results demonstrate that together ST2, ANG2, L-Ficolin, HA, and VCAM1 compose a biomarker panel for diagnosis of SOS. L-Ficolin, HA, and VCAM1 also stratified patients at risk for SOS as early as the day of HCT. Prognostic Bayesian modeling for SOS onset based on L-Ficolin, HA, and VCAM1 levels on the day of HCT and clinical characteristics showed >80% correct prognosis of SOS onset. These biomarkers may provide opportunities for preemptive intervention to minimize SOS incidence and/or severity.

Original languageEnglish (US)
Pages (from-to)1739-1745
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2015

Keywords

  • Biomarkers
  • Proteomics
  • Sinusoidal obstruction syndrome
  • SOS
  • Veno-occlusive disease
  • VOD

ASJC Scopus subject areas

  • Transplantation
  • Hematology

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    Akil, A., Zhang, Q., Mumaw, C. L., Raiker, N., Yu, J., Velez de Mendizabal, N., Haneline, L. S., Robertson, K. A., Skiles, J., Diaz-Ricart, M., Carreras, E., Renbarger, J., Hanash, S., Bies, R. R., & Paczesny, S. (2015). Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation. Biology of Blood and Marrow Transplantation, 21(10), 1739-1745. https://doi.org/10.1016/j.bbmt.2015.07.004