Different biology and clinical outcome according to the absolute numbers of clonal B-cells in monoclonal B-cell lymphocytosis (MBL)

Abstract

The biological and clinical relationship between Chronic Lymphocytic Leukaemia (CLL) and Monoclonal B-cell Lymphocytosis (MBL) has now been reported in some detail. This review investigates associations between biology and disease activity as they relate to the absolute numbers of abnormal cells. The clonal B-cells in CLL-type MBL are indistinguishable from CLL with respect to surface phenotype and the presence of chromosomal abnormalities. However, the majority of CLL-type MBL cases in the general population have very low numbers of clonal B-cells, typically in the range 0.1-10 per μL, and such cases use different IGHV genes than higher-count CLL-type MBL cases and often show intraclonal heterogeneity. Cases with higher counts are biologically similar to CLL although there is a relationship between the CLL cell count at presentation and the likelihood of further clonal expansion. Individuals presenting with CLL cell counts above 2,000 per μL are more likely to have gradually increasing B-cell counts over time and although the risk of requiring treatment for progressive CLL remains low there may be impaired normal B-cell activity.

FIG. 1.

The cumulative percentage of cases according to the absolute number of clonal B-cells for studies of individuals from the general population with a normal blood count (dotted line) and from series of individuals referred for clinical hematology investigations usually with a current or prior lymphocytosis (solid line). The clonal B-cell count in CLL-type MBL shows a marked difference in cases from population studies (median 1 clonal B-cell per μL with 95% of cases having less than 56 clonal B-cells per μL highlighted by the white background) compared to clinical hematology series (median 2,939 clonal B-cells per μL with 95% of cases having more than 447 clonal B-cells per μL highlighted by the dark grey background). Very few cases from either series have a clonal B-cell count within the same range as polyclonal B-cell levels in individuals with no detectable abnormal B-cells (light grey background).

FIG. 2.

Time course in an individual with CLL-type MBL presenting with a low CLL cell count and good prognostic markers. Absolute lymphocyte count is a poor measure of changing CLL count, and in individuals presenting with a low CLL cell count repeat flow cytometry is more informative for identifying rare cases with rapidly progressive disease. This individual was male, aged 52 at diagnosis, with mutated IGHV3–07 (6.5% deviation from germline) who did not respond to Chlorambucil or Fludarabine, and although there was a peripheral response to Alemtuzumab the bone marrow remained extensively infiltrated until treatment with Alemtuzumab and Fludarabine was initiated which eventually resulted in an MRD-negative complete response.