title: 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.
authors.affiliation: Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Shanique
authors.initials: S
authors.lastname: Palmer
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Luis F
authors.initials: LF
authors.lastname: Porrata
authors.forename: Betsy
authors.initials: B
authors.lastname: Laplant
authors.forename: Susan M
authors.initials: SM
authors.lastname: Geyer
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Bowen
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1