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: Andy C Rawstron, Fiona L Bennett, Sheila J M O'Connor, Marwan Kwok, James A L Fenton, Marieth Plummer, Ruth de Tute, Roger G Owen, Stephen J Richards, Andrew S Jack, Peter Hillmen
• Journal: The New England journal of medicine (N Engl J Med) Vol. 359 Issue 6 Pg. 575-83 (Aug 07 2008) ISSN: 1533-4406 [Electronic] United States
• PMID: 18687638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2008 Massachusetts Medical Society

Chemical References

• Genetic Markers
• Hemoglobins
• Immunoglobulin Heavy Chains

Topics

• Age Factors
• Aged
• Aged, 80 and over
• B-Lymphocytes (immunology)
• Cohort Studies
• DNA Mutational Analysis
• Disease Progression
• Female
• Genes, Immunoglobulin
• Genetic Markers
• Germ-Line Mutation
• Hemoglobins (analysis)
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Kaplan-Meier Estimate
• Leukemia, Lymphocytic, Chronic, B-Cell (immunology, mortality)
• Lymphocyte Count
• Lymphocytosis (immunology)
• Male
• Middle Aged
• Phenotype
• Precancerous Conditions (immunology)
• Prognosis
• Reference Values