Monoclonal B Cell Lymphocytosis

Multiparametric flow cytometry allows the detection of very small clones of monoclonal B-cells in peripheral blood from normal individuals. Population studies showed the prevalence of MBL to be 0.14% - 5.1%. The significance and long term implications of these is uncertain, and the term monoclonal B-cell lymphocytosis (MBL), as defined below, is recommended to distinguish these cases from patients with B-cell chronic lymphocytic leukemia (B-CLL). The diagnostic criteria for MBL and B-CLL were recently updated by the International Workshop on Chronic Lymphocytic Leukemia. (Blood 2008;111:5446-5456)

According to the recommendations from this workshop, the diagnostic criteria for MBL include the presence of a monoclonal B-cell population with:

  • B-cells in blood <5,000/µL
  • Absence of lymphadenopathy and hepatosplenomegaly (by physical examination and CT scans)
  • Absence of cytopenias due to marrow involvement by the monoclonal proliferation

The immunophenotype of the clonal B-cells of MBL is most often identical to that seen in B-CLL, with expression of B-cell markers CD19, CD20, and CD23, co-expression of CD5, and dim intensity of surface light chain expression. Other immuno-phenotypes are rare, including some cases that lack CD5 expression. (Br J Haematol 2007;139:701-708)

The relationship between MBL and B-CLL was investigated in a recent study from the United Kingdom. (N Engl J Med 2008;359:575-583) In this study, MBL with B-CLL immunophenotype was detected in 5.1% of 1520 individuals without lymphocytosis. Symptomatic B-CLL requiring treatment developed at the rate of 1.1% per year in a subset of these patients that were followed for a median of 6.7 y. In this respect, MBL is similar to monoclonal gammopathy of undetermined significance (MGUS), with a very low rate of progression to symptomatic disease.

Patients diagnosed with MBL based on flow cytometric evaluation of blood should be worked up to exclude B-CLL or other B-cell lymphoproliferative disorders, and then offered periodic follow up to watch for progression.

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