title: High serum levels of B-lymphocyte stimulator are associated with clinical-pathological features and outcome in classical Hodgkin lymphoma.
abstract: 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 clinical-pathological 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 4493.9 +/- 264.9 pg/ml vs. 2687.0 +/- 200.9 pg/ml; P < 0.0001). Levels above the median value (4242.0 pg/ml) were associated with age > or = 45 years (P = 0.042), advanced stages of disease (P = 0.005), systemic symptoms (P = 0.014) and extranodal involvement (P = 0.009). Five-year failure-free survival (FFS) of patients with sBLyS below or equal to median levels was 88.6% as compared to 65.1% of those with levels above the median (P = 0.009). Statistical analyses confirmed the prognostic significance of sBLyS (P = 0.046). 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.
authors.affiliation: Section of Haematology, Department of Clinical and Experimental Medicine, Verona University, Verona, Italy. cristina.tecchio@univr.it
authors.forename: C
authors.initials: C
authors.lastname: Tecchio
authors.forename: G
authors.initials: G
authors.lastname: Nadali
authors.forename: P
authors.initials: P
authors.lastname: Scapini
authors.forename: C
authors.initials: C
authors.lastname: Bonetto
authors.forename: C
authors.initials: C
authors.lastname: Visco
authors.forename: N
authors.initials: N
authors.lastname: Tamassia
authors.forename: T P
authors.initials: TP
authors.lastname: Vassilakopoulos
authors.forename: G A
authors.initials: GA
authors.lastname: Pangalis
authors.forename: F
authors.initials: F
authors.lastname: Calzetti
authors.forename: B
authors.initials: B
authors.lastname: Nardelli
authors.forename: V
authors.initials: V
authors.lastname: Roschke
authors.forename: M
authors.initials: M
authors.lastname: Gottardi
authors.forename: F
authors.initials: F
authors.lastname: Zampieri
authors.forename: F
authors.initials: F
authors.lastname: Gherlinzoni
authors.forename: F
authors.initials: F
authors.lastname: Facchetti
authors.forename: G
authors.initials: G
authors.lastname: Pizzolo
authors.forename: M A
authors.initials: MA
authors.lastname: Cassatella
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006689:Hodgkin Disease / Q000097:blood* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D053264:B-Cell Activating Factor; D014408:Biomarkers, Tumor