Anemia in Diffuse Large B cell Non-Hodgkin Lymphoma: The Role of IL-6, Hepcidin and Erythropoietin

Anemia is a frequent sign in patients with diffuse large B cell lymphoma (DLBCL) at diagnosis. We determined erythropoietin, hepcidin, and IL-6 in plasma samples of 53 patients with DLBCL. The majority of patients (40/53, 75%) showed defective endogenous erythropoietin production, in particular when anemia was present (p=0.01). Hepcidin plasma levels were significantly higher in patients compared to controls (p=0.006), particularly in those with characteristics associated with a more active disease, including elevated LDH (p=0.0004), B-symptoms (p=0.07) and an age-adjusted IPI score >1 (p=0.01). Hepcidin levels strongly correlated to ferritin (r=0.77, p<0.0001) and weakly to IL-6 concentrations (r=0.30, p=0.03), but not to haemoglobin values. IL-6 inversely correlated to haemoglobin values both in univariate and multivariate analysis (p=0.04), including hepcidin and erythropoietin as variables. Our findings suggest that elevated hepcidin levels and inadequate erythropoietin response are frequent in DLBCL, but elevated IL-6 plays the major role for the development of anemia.