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Prognostic importance of T and NK-cells in a consecutive series of newly diagnosed patients with chronic lymphocytic leukaemia
Authors:Palmer Shanique  Hanson Curtis A  Zent Clive S  Porrata Luis F  Laplant Betsy  Geyer Susan M  Markovic Svetomir N  Call Timothy G  Bowen Deborah A  Jelinek Diane F  Kay Neil E  Shanafelt Tait D
Institution:Department of Internal Medicine;, Department of Laboratory Medicine and Pathology;, Division of Hematology;, Mayo Clinic Department of Cancer Center Statistics;, and Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA
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.
Keywords:chronic lymphocytic leukaemia  prognosis  immune system  T-cells  natural killer cells
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