title: Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia.
abstract: The clinical relevance of angiopoietin-2 (Ang2) in chronic lymphocytic leukemia (CLL) was previously suggested by the association between high Ang2, and shorter progression-free survival reported in small series of patients. Here, we evaluated Ang2 glycoprotein levels in plasma samples collected from a multicentric cohort of CLL patients (n = 316) using an enzyme-linked immunosorbent assay method, and we investigated its prognostic role in relation to time to first treatment (TTFT) and overall survival. Based on a cutoff equal to 2459 pg/mL, we divided our cohort in 2 subsets (high and low Ang2) composing 100 (31.6%) and 216 (68.4%) patients, respectively. High Ang2 was predictive of reduced TTFT (P < .001) and overall survival (P = .002). Multivariate analysis confirmed that high Ang2 was an independent prognosticator for TTFT (hazard ratio = 1.739; 95% confidence interval, 1.059-2.857; P = .029). Significant associations were found between high Ang2 and advanced Binet stages (P < .001), high beta(2)-microglobulin (P < .001), unmutated variable region of immunoglobulin heavy chain gene status (P < .001), high CD38 and zeta-chain-associated protein kinase 70 expression (P < .001 and P = .003), and intermediate/high cytogenetic risk (P = .005). Moreover, Ang2 added prognostic power to other conventional prognosticators and helped to refine prognosis among CLL subsets with both high and low vascular endothelial growth factor plasma levels. Ang2 plasma level may be a useful independent prognosticator for CLL.
authors.affiliation: Hematology Unit, Department of Oncology and Hematology, University of Modena and Reggio Emilia, Via Del Pozzo 71, Modena, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Maffei
authors.forename: Silvia
authors.initials: S
authors.lastname: Martinelli
authors.forename: Rita
authors.initials: R
authors.lastname: Santachiara
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Carla
authors.initials: C
authors.lastname: Guarnotta
authors.forename: Elisa
authors.initials: E
authors.lastname: Sozzi
authors.forename: Antonella
authors.initials: A
authors.lastname: Zucchetto
authors.forename: Gian Matteo
authors.initials: GM
authors.lastname: Rigolin
authors.forename: Stefania
authors.initials: S
authors.lastname: Fiorcari
authors.forename: Ilaria
authors.initials: I
authors.lastname: Castelli
authors.forename: Marcella
authors.initials: M
authors.lastname: Fontana
authors.forename: Valeria
authors.initials: V
authors.lastname: Coluccio
authors.forename: Giovanna
authors.initials: G
authors.lastname: Leonardi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zucchini
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Francesco
authors.initials: F
authors.lastname: Forconi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Torelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000032:analysis / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D001774:Blood Chemical Analysis; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000175:diagnosis* / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D042702:Angiopoietin-2; D014408:Biomarkers, Tumor