title: Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.
abstract: BACKGROUND
  Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression.
  
  
  METHODS
  T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data.
  
  
  RESULTS
  The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028).
  
  
  CONCLUSIONS
  Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia.
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Third Medical Department With Hematology, Medical Oncology, Hemostaseology, Rheumatology, and Infectious Disease of the Private Medical University Hospital of Salzburg, Salzburg, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Weiss
authors.forename: Thomas
authors.initials: T
authors.lastname: Melchardt
authors.forename: Alexander
authors.initials: A
authors.lastname: Egle
authors.forename: Christoph
authors.initials: C
authors.lastname: Grabmer
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Inge
authors.initials: I
authors.lastname: Tinhofer
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000188:drug therapy; D018655:Lymphocyte Count; D011379:Prognosis; D012306:Risk; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors