title: Baff serum level predicts time to first treatment in early chronic lymphocytic leukemia.
abstract: We analyzed the correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukemia (CLL) [i.e. mutational status of the immunoglobulin heavy chain variable region (IgVH), ZAP-70 and CD38 expression] and serum levels of B cell-activating factor (BAFF of the TNF family) by evaluating the impact of these variables on the time to first treatment (TFT) in a series of 169 previously untreated CLL patients in Binet stage A. Higher levels of BAFF were more frequently associated with female gender (P=0.02), younger age (P=0.01), Rai stage 0 (P=0.002), higher platelet count (P=0.005), mutated IgVH disease (P=0.002), higher occurrence of normal cytogenetic profile or presence of 13q deletion (P=0.02), low ZAP-70- (P=0.003), and CD38-expression (P=0.02). Maximally selected log-rank statistic plot identified a serum BAFF concentration of 0.313 ng/mL as the best cut-off (P<0.0001). This threshold recognized two subsets of patients with different TFT (P<0.0001). Because in multivariate analysis soluble BAFF [Hazard ratio (HR), 8.23; confidence Interval (CI) 95%,3.0-22.6, P<0.0001] and mutational status of IgVH (HR=2.60; CI 95% 1.10-6.14, P=0.03) maintained the discriminating power their combined effect on clinical outcome was assessed. When three groups were considered: (1) low-risk (n=93), patients with concordant IgVH(mut) and higher soluble BAFF; (2) intermediate-risk (n=50), patients with IgVH(mut) and low BAFF levels or IgVH(unmut) and soluble higher BAFF;(3) high-risk (n=26), patients with concordant IgVH (unmut) and low soluble BAFF, the 2-yr TFTs were, respectively, 95%, 85%, and 41% (P<0.0001). In conclusion, our results indicate that in early B-cell CLL, the biological profile including among other parameters soluble BAFF may provide a useful insight into the complex interrelationship of prognostic variables.
authors.affiliation: Medical Oncology Unit, Hematology-Oncology Department, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy. smolica@libero.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Molica
authors.forename: Giovanna
authors.initials: G
authors.lastname: Digiesi
authors.forename: Caterina
authors.initials: C
authors.lastname: Battaglia
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.forename: Anna
authors.initials: A
authors.lastname: Antenucci
authors.forename: Matteo
authors.initials: M
authors.lastname: Molica
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D053264:B-Cell Activating Factor / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis
chemical_list: D053264:B-Cell Activating Factor; D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1