Prognostic importance of T and NK-cells in a consecutive series of newly diagnosed patients with chronic lymphocytic leukaemia

Abstract

Patients with chronic lymphocytic leukaemia (CLL) have a variable clinical course. The identification of modifiable characteristics related to CLL-specific survival may provide opportunities for therapeutic intervention. The absolute number of T-cell and natural killer (NK)-cells was calculated for 166 consecutive patients with CLL evaluated by flow cytometry at Mayo Clinic < or = 2 months of diagnosis. The size of the T-cell/NK-cell compartment relative to the size of the malignant monoclonal B-cell (MBC) compartment was evaluated by calculating NK:MBC and T:MBC ratios. Patients exhibited substantial variation in the absolute number of T- and NK-cells as well as T:MBC and NK:MBC ratios at diagnosis. Higher T:MBC and NK:MBC ratios were observed among patients with early stage and mutated IGHV genes (all P < or = 0.0003). As continuous variables, both T:MBC ratio (P-value = 0.03) and NK:MBC ratio (P-value = 0.02) were associated with time to treatment (TTT). On multivariate Cox modelling including stage, CD38, absolute MBC count, NK:MBC ratio and T:MBC ratio, the independent predictors of TTT were stage, T:MBC ratio and NK:MBC ratio. These findings suggest that measurable characteristics of the host immune system relate to the rate of disease progression in patients with newly diagnosed CLL. These characteristics can be modified and continued evaluation of immunomodulatory drugs, vaccination strategies and cellular therapies to delay/prevent disease progression are warranted.

Fig. 1A

Distribution of Absolute T-cell and NK-cell # at diagnosis Distribution Absolute T-cell # at diagnosis (×10⁹/L)

Fig. 1B

Distribution of Absolute T-cell and NK-cell # at diagnosis Distribution Absolute NK-cell # at diagnosis (×10⁹/L)

Fig. 2A

Relationship Between TTT and Median MBC and Median T:MBC and NK:MBC ratios Patient TTT stratified based on the median MBC

Fig. 2B

Relationship Between TTT and Median MBC and Median T:MBC and NK:MBC ratios Patient TTT stratified based on the median T:MBC ratio

Fig. 2C

Relationship Between TTT and Median MBC and Median T:MBC and NK:MBC ratios Patient TTT stratified based on the median NK:MBC ratio

Fig. 3A

Relationship Between TTT and Statistically Derived Thresholds to Classify MBC and T:MBC and NK:MBC ratios Patient TTT stratified based on the MBC count that best stratifies outcome

Fig. 3B

Relationship Between TTT and Statistically Derived Thresholds to Classify MBC and T:MBC and NK:MBC ratios Patient TTT stratified based on the T:MBC Ratio that best stratifies outcome

Fig. 3C

Relationship Between TTT and Statistically Derived Thresholds to Classify MBC and T:MBC and NK:MBC ratios Patient TTT stratified based on the NK:MBC Ratio that best stratifies outcome