Plasma Circulating Ki-67 Index as a Biomarker and Prognostic Indicator in Patients with Chronic Lymphocytic Leukemia.

Abstract 1261

Poster Board I-283

Ki-67 is a nuclear antigen that is expressed in all stages of the cell cycle except G₀ and is widely used as a marker of cellular proliferation in human tumors. We recently demonstrated that levels of plasma circulating Ki-67 (cKi-67) are significantly higher in patients with newly diagnosed acute lymphoblastic leukemia (ALL) than in healthy control subjects, and that elevated levels of cKi-67 are associated with a shorter survival in ALL patients. Here we examined the associations of cKi-67 levels with laboratory and clinical variables in patients with chronic lymphocytic leukemia (CLL). The study included 194 patients with CLL and 96 healthy control subjects. The cKi-67 levels in plasma were determined using electro-chemiluminescence-based immunoassay using the Mesoscale Discovery platform. Since usually Ki-67 is used as an index of tumor cell proliferation, we took into account the lymphocyte count of the CLL patients in peripheral blood and normalized the levels of the cKi67 to the absolute number of lymphocytes in the peripheral blood establishing plasma cKI-67 index (cKi-67 level ng/1000 circulating lymphocytes/μL plasma). Median (range) levels of absolute cKi-67 were significantly higher in patients with CLL than in control subjects (914.65 [102.0-4975.12] ng/mL vs 353 [35.76-2830.65] ng/mL; P<0.0001). However, absolute levels did not correlate with clinical or other laboratory variables (white cell count, hemoglobin, platelets, beta-2 microglobulin, or Rai stage, performance status). In contrast, the cKI-67 index correlated significantly with bone marrow involvement (p<0.001), number of lymph node sites involved (p<0.001), and Rai stage (p=0.05), but not with IgV_H mutation (P=0.62) or performance status (p=0.71) The cK-I67 index was significantly associated with survival when used as either as a continuous variable (P=0.002) or as a dichotomous variable (P=0.005). Multivariate Cox proportional hazards analysis incorporating cKi67 index with IgVH mutation status and B2M, demonstrated that only cKi-67 and B2M were independent predictors of survival.

This data shows that there variability in proliferation between patients with CLL and those patients high relative proliferation (index) have more aggressive disease. Furthermore, plasma cKi-67 index and B2M levels are strong predictors of clinical behavior in CLL.