High serum levels of B-lymphocyte stimulator are associated with clinical-pathological features and outcome in classical Hodgkin lymphoma

Summary B-lymphocyte stimulator (BLyS) acts as survival factor for B lymphocytes. As Hodgkin and Reed-Sternberg (HRS) cells express receptors through which BLyS promotes their growth and chemotherapy resistance, we investgated whether this molecule was increased in sera from patients with classical Hodgkin lymphoma (cHL) and whether it correlates with clinicalpathological features and outcomes. Enzyme-linked immunosorbent assay was used to measure soluble BLyS (sBLyS) in sera from 87 patients and 33 donors; higher levels were detected in patients (mean ± standard error 4493AE9 ± 264AE9 pg/ml vs. 2687AE0 ± 200AE9 pg/ml; P <0 AE0001). Levels above the median value (4242AE0 pg/ml) were associated with age ‡45 years (P ¼ 0AE042), advanced stages of disease (P ¼ 0AE005), systemic symptoms (P ¼ 0AE014) and extranodal involvement (P ¼ 0AE009). Five-year failure-free survival (FFS) of patients with sBLyS below or equal to median levels was 88AE6% as compared to 65AE1% of those with levels above the median (P ¼ 0AE009). Statistical analyses confirmed the prognostic significance of sBLyS (P ¼ 0AE046). When patients were analysed according to variables associated with high levels, sBLyS showed an independent predictive power in terms of FFS. Our findings support the involvement of BLyS in cHL pathogenesis. The association between high serum levels and an inferior FFS indicates that sBLyS is a possible prognostic predictor with a potential significance as a therapeutic target.