Four-Biomarker Panel Identified for Chronic Graft-vs-Host Disease

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In a study reported in the Journal of Clinical Oncology, Jeffrey Yu, MD, of the Indiana University School of Medicine, Indianapolis, and colleagues identified a four-biomarker panel that was predictive of chronic graft-vs-host disease after allogeneic hematopoietic cell transplantation.

Discovery Cohort

In the study, a quantitative proteomics approach was used to compare pooled plasma samples from matched time points after hematopoietic cell transplantation (median = 103 days) from 35 patients with and 18 patients without chronic graft-vs-host disease. Of a total of 105 proteins showing a ≥ 1.25-fold difference in expression, 24 were selected for additional analysis on the basis of involvement in relevant pathways and availability of enzyme-linked immunosorbent assays.

Verification Cohorts

Of the 24 proteins, 9 were associated with chronic graft-vs-host disease in a first independent verification cohort (n = 211; 178 with chronic graft-vs-host disease and 33 controls); use of 4 proteins (ST2, CXCL9, matrix metalloproteinase 3, and osteopontin) was sufficient for a panel with an area under the receiver operating characteristic curve (AUC) of 0.89 and significant correlation with chronic graft-vs-host disease diagnosis, chronic graft-vs-host disease severity, and nonrelapse mortality.

In a second validation cohort (n = 180; 87 with chronic graft-vs-host disease, 93 controls), the panel exhibited an AUC of 0.75; at day +100, the panel predicted chronic graft-vs-host disease within the following 3 months at an AUC of 0.67 without use of known clinical risk factors and at an AUC of 0.79 when used in combination with known clinical risk factors.

The investigators concluded: “We conclude that the biomarker panel measured at diagnosis or day +100 after hematopoietic cell transplantation may allow patient stratification according to risk of [chronic] graft-vs-host disease.”

The study was supported by the National Marrow Donor Program, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. ■

Yu J, et al: J Clin Oncol. May 23, 2016 (early release online).