What to do about: Low level monoclonal B-lymphocyte populations

In recent years, flow cytometric analysis of the blood and bone marrow has become a standard of practice for the evaluation of patients having hematologic abnormalities, primarily for the identification of hematolymphoid neoplasms. Multiparameter flow cytometry instrumentation and analysis software has made it possible to identify small populations of circulating monoclonal B-lymphocytes in patients with non-Hodgkin lymphoma, as well as, in patients who are healthy and asymptomatic with no clinical evidence of lymphoma. The latter group is characterized by the presence of a low level monoclonal B-lymphocyte population, which is not associated with an absolute lymphocytosis and usually comprises less than 1% of the cellular events analyzed by flow cytometry.

The identification of a small clonal B-cell population is almost always an incidental finding when a patient’s bone marrow or peripheral blood is being evaluated by flow cytometry for an unrelated reason. The clonal B-lymphocyte populations are usually persistent in most patients. They may have a CLL-like immunophenotype characterized by the expression of CD5 and CD23, or they may exhibit a variety of non-CLL phenotypes, including: CD5-/CD10-, CD5+/CD23-, CD10+, CD25+/CD103+ (hairy cell-like), and CD5+/CD23-/FMC7+ (mantle cell-like). The CLL-like phenotype is the most common, reported to be present in 3.5%-5.5% healthy adults or elderly persons with normal blood counts, while the non-CLL phenotypes have been reported in 1%-1.4% of healthy individuals.

The cause and clinical significance of these populations is unknown but they should not be ignored as evidenced by one study which reported that at least 29% of their cases having small clonal B-lymphocyte populations represented manifestations of early or clinically occult NHL. The true risk of progression to overt NHL is unknown however and may take several years to develop, if at all, similar to monoclonal gammopathies of undetermined significance. Some of these populations may be associated with autoimmune diseases or be age-related. Although no name has been given to this enitiy, it is perhaps appropriate to use the term, “monoclonal B-lymphocytes of undetermined significance.”

The clinician having a patient with this finding must address important two issues. The first is to assess whether the patient has any evidence of a lymphoproliferative disease. This will require a thorough evaluation, the extent of which will have to be determined on a case by case basis and depend on several factors. None the less there will need to be correlation with the clinical history and physical findings, as well as, the peripheral blood and bone marrow morphology to determine if there is an underlying lymphoproliferative disorder that would account for the clonal B-lymphocytes. If after a thorough evaluation no underlying cause is found, then it is probably safe to assume that the clonal lymphocyte population is of uncertain significance and that periodic monitoring of the patient is warranted. If a patient has a history of NHL, the immunophenotype of the clonal B-lymphocyte population must be correlated with that of the lymphoma to determine if it is the same process.

The second issue is how often to monitor the patient for possible progression or resolution. Given that the risk of progression to clinical disease is unknown and probably infrequent, it would be prudent to monitor a patient’s CBC and general health at least yearly. Repeat flow cytometric analysis would be dependent on a change in the patient’s condition, suggesting progression, but is ultimately at the discretion of the treating physician.