Format

Send to

Choose Destination
Biol Blood Marrow Transplant. 2015 Oct;21(10):1739-45. doi: 10.1016/j.bbmt.2015.07.004. Epub 2015 Jul 11.

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

Author information

1
Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana.
2
Department of Genomics, Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
4
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
5
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
6
Hospital Clinic, IDIBAPS, Barcelona, Spain.
7
Hospital Clinic, IDIBAPS, Barcelona, Spain; José Carreras Foundation & Leukemia Research Institute, Barcelona, Spain.
8
Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
9
Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, University of Texas MD Anderson Cancer Center, Houston, Texas.
10
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: sophpacz@iu.edu.

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.

KEYWORDS:

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

PMID:
26172478
PMCID:
PMC4568166
DOI:
10.1016/j.bbmt.2015.07.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center