CXCL9 predicts Severity at Onset of Chronic Graft-Versus-Host Disease

BACKGROUND: Chronic graft-versus-host disease (cGVHD) represents a double-edged sword. In its nonsevere form, cGVHD associates with better control of the malignant disease, thus highlighting graft-versus-leukemia effects. However, severe cGVHD leads to debilitating morbidity and increased nonrelapse mortality. The prediction of severe cGVHD, in particular at disease onset, is therefore of high importance for ensuing clinical decisions and overall success of allogeneic stem cell transplantations (alloSCT).CXCL9 is an interferon-inducible chemokine of the CXC family and is increased in cGVHD. Endothelial activation and stress index (EASIX) was shown to predict death after acute GVHD. We explored CXCL9 and EASIX as predictors of severe cGVHD. PATIENTS AND METHODS: Sera and clinical data were available of 480 patients who survived at least 6 months following alloSCT without steroid-refractory acute GVHD and without early relapse. CXCL9 and EASIX were measured on day +100 and onset of cGVHD. RESULTS: Development of nonsevere cGVHD was significantly associated with improved overall survival (HR 0.53, p<0.001). CXCL9 serum levels at onset of cGVHD predicted the development of severe cGVHD later on (HR 1.33, p=0.02). In contrast, EASIX at onset of cGVHD was not associated with cGVHD severity but was a significant independent risk factor for overall mortality and NRM. CONCLUSION: CXCL9 levels at the onset of cGVHD can help to predict severe courses of the disease and have potential for optimizing tailored administration of immunosuppressive therapy.