title: Plasma interleukin 8 level predicts for survival in chronic lymphocytic leukaemia.
abstract: The malignant B cells of patients with chronic lymphocytic leukaemia (CLL) constitutively express interleukin 8 (IL-8) and IL-8 receptors. Ex vivo culture with exogenous IL-8 enhances IL-8 expression and prolongs leukaemia cell survival, partly through increased bcl-2 expression. IL-8 may function as an autocrine growth and apoptosis resistance factor in CLL. Therefore, we evaluated the prognostic relevance of plasma IL-8 levels in 151 CLL patients [median age 61 years (range, 32-84 years), median plasma IL-8 level 18.9 pg/ml (9.1-89.1 pg/ml)]. All Rai stages were represented; advanced stage was associated with significantly higher plasma IL-8 levels (P < 0.0001, Kruskal-Wallis). Also, plasma IL-8 level was correlated with serum beta2-microglobulin (beta2-M) (R = 0.24, P = 0.0081), haemoglobin (R = -0.39, P < 0.0001) and platelet count (R = -0.23, P = 0.0049) by Spearman's rank correlation. Univariate analysis using Cox proportional hazards models identified elevated IL-8 and beta2-M as significant prognostic factors with relative risks of 7.43 (P = 9.1 x 10(-9)) and 16.40 (P = 5.9 x 10(-10)) respectively. High levels of IL-8 were associated with shorter survival independent of beta2-M level. Using recursive-partitioning procedures, an IL-8 cut-off point of 26.2 pg/ml segregated a group of CLL patients with significantly shorter survival (median 9.3 months) (P < 0.0001). In conclusion, plasma IL-8 level in CLL patients correlates with other prognostic factors, such as Rai stage and beta2-M, and is associated with increased risk of death in CLL patients. The role of IL-8 inhibitors in the treatment of patients with CLL should be explored.
authors.affiliation: Department of Leukaemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Do
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.forename: Amanda
authors.initials: A
authors.lastname: Dey
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010976:Platelet Count; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D016209:Interleukin-8; D001613:beta 2-Microglobulin