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Blood. 2016 Jun 16;127(24):3082-91. doi: 10.1182/blood-2015-09-668251. Epub 2016 Mar 28.

Heterogeneity of chronic graft-versus-host disease biomarkers: association with CXCL10 and CXCR3+ NK cells.

Author information

1
Michael Cuccione Childhood Cancer Research Program, British Columbia Children's Hospital/University of British Columbia, Vancouver, BC, Canada;
2
Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN;
3
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, University of Montreal, Montreal, QC, Canada;
4
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA;
5
Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany;
6
University of Calgary, Calgary, AB, Canada;
7
King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
8
Dana-Farber Cancer Institute, Boston, MA;
9
Centre Hospitalier Universitaire de Quebec, Hopital Enfant-Jesus, Quebec City, QC, Canada;
10
Princess Margaret Cancer Centre, Toronto, ON, Canada;
11
Leukemia/Bone Marrow Transplant Program of British Columbia, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;
12
Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, OR;
13
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
14
McGill University Health Center, Montreal, QC, Canada;
15
CancerCare Manitoba, Winnipeg, MB, Canada;
16
Ottawa Hospital Research Institute, Ottawa, ON, Canada;
17
Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; and.
18
Queen Elizabeth II Health Science Centre, Halifax, NS, Canada.

Abstract

Chronic graft-versus-host disease (cGVHD) remains one of the most significant long-term complications after allogeneic blood and marrow transplantation. Diagnostic biomarkers for cGVHD are needed for early diagnosis and may guide identification of prognostic markers. No cGVHD biomarker has yet been validated for use in clinical practice. We evaluated both previously known markers and performed discovery-based analysis for cGVHD biomarkers in a 2 independent test sets (total of 36 cases ≤1 month from diagnosis and 31 time-matched controls with no cGVHD). On the basis of these results, 11 markers were selected and evaluated in 2 independent replication cohorts (total of 134 cGVHD cases and 154 controls). cGVHD cases and controls were evaluated for several clinical covariates, and their impact on biomarkers was identified by univariate analysis. The 2 replications sets were relatively disparate in the biomarkers they replicated. Only sBAFF and, most consistently, CXCL10 were identified as significant in both replication sets. Other markers identified as significant in only 1 replication set included intercellular adhesion molecule 1 (ICAM-1), anti-LG3, aminopeptidase N, CXCL9, endothelin-1, and gelsolin. Multivariate analysis found that all covariates evaluated affected interpretation of the biomarkers. CXCL10 had an increased significance in combination with anti-LG3 and CXCL9, or inversely with CXCR3(+)CD56(bright) natural killer (NK) cells. There was significant heterogeneity of cGVHD biomarkers in a large comprehensive evaluation of cGVHD biomarkers impacted by several covariates. Only CXCL10 strongly correlated in both replication sets. Future analyses for plasma cGVHD biomarkers will need to be performed on very large patient groups with consideration of multiple covariates.

PMID:
27020088
PMCID:
PMC4911864
DOI:
10.1182/blood-2015-09-668251
[Indexed for MEDLINE]
Free PMC Article

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