Plasma interleukin 8 level predicts for survival in chronic lymphocytic leukaemia

Summary. 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 β2‐microglobulin (β2‐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 β2‐M as significant prognostic factors with relative risks of 7·43 (P = 9·1 × 10−9) and 16·40 (P = 5·9 × 10−10) respectively. High levels of IL‐8 were associated with shorter survival independent of β2‐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 β2‐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.