Lymphocytosis and chronic leukaemia

Abstract

Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia among the elderly in the developed world. It is less frequent in India and other developing countries, but its incidence is increasing possibly as a result of a longer lifespan and changing lifestyle. The diagnosis of CLL requires an absolute lymphocyte count of >5000/cmm with the presence of monoclonality evidenced by characteristic cell-surface phenotype of B cells on flow cytometry: the presence of CD19, CD5 and CD23; weak expression of CD20 and CD79b; and either kappa or lambda immunoglobulin light chains. Some adults (3%) who have an absolute lymphocyte count of <5000/ cmm but express CLL-like cell surface phenotype are said to have 'monoclonal B-cell lymphocytosis (MBL) of uncertain significance'. The biological importance of this finding is unclear. In this study, Rawstron et al. studied two cohorts-one comprising 1520 subjects with normal blood counts and the other of 2228 subjects with lymphocytosis (defined as >4000 lymphocytes/cmm) for the presence of monoclonal B-cell population using flow cytometry. Cytogenetic and molecular characterization of the monoclonal B-cell population was done and a small group of 185 subjects with MBL was followed for a median period of 6.7 years (range: 0.2-11.8 years). The first cohort had persons 60-80 years of age who were attending outpatient departments of various specialties except haematology, oncology and a transplant clinic and they had a normal total leucocyte count, platelet count and haemoglobin. The second cohort consisted of subjects referred for current or previous lymphocytosis between April 1995 and December 2000. Among the first cohort (normal blood counts), 78 (5.1%) were found to have CLL-phenotype MBL and 27 (1.8%) had non-CLLphenotype MBL. In the second cohort, 309 (13.9%) had CLLphenotype MBL and the rest had CLL (46.3%) or reactive lymphocytosis (39.9%). Of the 71 subjects with CLL-phenotype MBL in either cohort (analysed by FISH), 13q14 del, trisomy 12, 11q23 del and 17p del were detected in 39% ,18%, 0% and 0% in the first cohort with normal blood counts, and in 58%, 21%, 6% and 3% in the second cohort (with lymphocytosis). Immunoglobulin heavy variable group (IGHV) mutation was detected in 85% of the subjects with MBL with normal counts and 90% of those with MBL with lymphocytosis. Follow up was not available for those with MBL and normal counts as the samples were anonymous. However, 185 of the subjects with MBL and lymphocytosis (second cohort) were followed for 6.7 years; progressive lymphocytosis developed in 51 (28%) of these. Among those with progressive lymphocytosis, further evidence of progressive CLL (lymphadenopathy, hepatomegaly, splenomegaly, lymphocyte doubling time <6 months and drenching sweats) developed in 28 (55%). Thirteen of the 51 subjects eventually required chemotherapy. Baseline B-cell count was the only factor that predicted progressive lymphocytosis; subjects with a baseline B-cell count <1900/cmm rarely progressed.