title: Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia.
abstract: BACKGROUND
  A diagnosis of chronic lymphocytic leukemia (CLL) requires a count of over 5000 circulating CLL-phenotype cells per cubic millimeter. Asymptomatic persons with fewer CLL-phenotype cells have monoclonal B-cell lymphocytosis (MBL). The goal of this study was to investigate the relation between MBL and CLL.
  
  
  METHODS
  We investigated 1520 subjects who were 62 to 80 years of age with a normal blood count and 2228 subjects with lymphocytosis (>4000 lymphocytes per cubic millimeter) for the presence of MBL, using flow cytometry. Monoclonal B cells were further characterized by means of cytogenetic and molecular analyses. A representative cohort of 185 subjects with CLL-phenotype MBL and lymphocytosis were monitored for a median of 6.7 years (range, 0.2 to 11.8).
  
  
  RESULTS
  Monoclonal CLL-phenotype B cells were detected in 5.1% of subjects (78 of 1520) with a normal blood count and 13.9% (309 of 2228) with lymphocytosis. CLL-phenotype MBL had a frequency of 13q14 deletion and trisomy 12 similar to that of CLL and showed a skewed repertoire of the immunoglobulin heavy variable group (IGHV) genes. Among 185 subjects presenting with lymphocytosis, progressive lymphocytosis occurred in 51 (28%), progressive CLL developed in 28 (15%), and chemotherapy was required in 13 (7%). The absolute B-cell count was the only independent prognostic factor associated with progressive lymphocytosis. During follow-up over a median of 6.7 years, 34% of subjects (62 of 185) died, but only 4 of these deaths were due to CLL. Age above 68 years and hemoglobin level below 12.5 g per deciliter were the only independent prognostic factors for death.
  
  
  CONCLUSIONS
  The CLL-phenotype cells found in the general population and in subjects with lymphocytosis have features in common with CLL cells. CLL requiring treatment develops in subjects with CLL-phenotype MBL and with lymphocytosis at the rate of 1.1% per year.
authors.affiliation: Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds, United Kingdom. andy.rawstron@hmds.org.uk
authors.forename: Andy C
authors.initials: AC
authors.lastname: Rawstron
authors.forename: Fiona L
authors.initials: FL
authors.lastname: Bennett
authors.forename: Sheila J M
authors.initials: SJ
authors.lastname: O'Connor
authors.forename: Marwan
authors.initials: M
authors.lastname: Kwok
authors.forename: James A L
authors.initials: JA
authors.lastname: Fenton
authors.forename: Marieth
authors.initials: M
authors.lastname: Plummer
authors.forename: Ruth
authors.initials: R
authors.lastname: de Tute
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Richards
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Jack
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005803:Genes, Immunoglobulin; D005819:Genetic Markers; D018095:Germ-Line Mutation; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000401:mortality; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011230:Precancerous Conditions / Q000276:immunology*; D011379:Prognosis; D012016:Reference Values
chemical_list: D005819:Genetic Markers; D006454:Hemoglobins; D007143:Immunoglobulin Heavy Chains