Journal
BLOOD
Volume 123, Issue 5, Pages 786-793Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-08-520072
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Funding
- RayBiotech
- Briskin/Schlafer Pediatric Oncology Investigators Fund
- University of Michigan Pediatric Hematology/Oncology Junior Faculty Grant
- National Marrow Donor Program [200513, R01CA174667]
- Chronic GVHD Consortium part of the NIH Rare Diseases Clinical Research Network [U54 CA163438]
- [R01CA118953]
- [U54CA163438]
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There are no validated biomarkers for chronic GVHD (cGVHD). We used a protein microarray and subsequent sequential enzyme-linked immunosorbent assay to compare 17 patients with treatment-refractory de novo-onset cGVHD and 18 time-matched control patients without acute or chronic GVHD to identify 5 candidate proteins that distinguished cGVHD from no cGVHD: CXCL9, IL2R alpha, elafin, CD13, and BAFF. We then assessed the discriminatory value of each protein individually and in composite panels in a validation cohort (n=109). CXCL9 was found to have the highest discriminatory value with an area under the receiver operating characteristic curve of 0.83 (95% confidence interval, 0.74-0.91). CXCL9 plasma concentrations above the median were associated with a higher frequency of cGVHD even after adjustment for other factors related to developing cGVHD including age, diagnosis, donor source, and degree of HLA matching (71% vs 20%; P < .001). A separate validation cohort from a different transplant center (n 5 211) confirmed that CXCL9 plasma concentrations above the median were associated with more frequent newly diagnosed cGVHD after adjusting for the aforementioned factors (84% vs 60%; P = .001). Our results confirm that CXCL9 is elevated in patients with newly diagnosed cGVHD.
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