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

Publication Type:

Journal Article

Source:

Blood, Volume 127, Issue 24, p.3082-3091 (2016)

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 two independent test sets (total of 36 cGvHD≤ one month from diagnosis and 31 time matched controls with no cGvHD). Based on these results, 11 markers were selected and evaluated in two independent replication cohorts (total of 134 cGvHD and 154 controls). cGvHD cases and controls were evaluated for a number of clinical co-variates and their impact on biomarkers identified by univariate analysis. The two 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 ICAM1, 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)NK cells. There was significant heterogeneity of cGvHD biomarkers in a large comprehensive evaluation of cGvHD biomarkers impacted by a number of 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 co-variates.