Monoclonal Lymphocytosis of Undetermined Significance (MLUS)

When Kanti Rai wrote his brilliant paper on CLL staging in 1975 you needed an absolute lymphocyte count of 15K to be diagnosed as CLL. Since then we have been able to recognise the distinct CLL immunophenotype of CD5, CD19, CD23, low surface Ig, and low CD79b. This has meant that we no longer needed such a high lymphocyte count to distinguish CLL from other causes of a lymphocytosis. Consequently the threshold came down to 5K.

But Andy Rawstron has shown us that if you look carefully with 4 color flow, you can pick out a population of cells with this immunophenotype in 3.5% of the population over 40. An International group has called this Monoclonal B cell Lymphocytosis (MBL) although others like the term MLUS (recognising that it bears a similar relationship to CLL as MGUS does to myeloma).

Several years ago the French and the Spanish groups both described "smoldering CLL" with lymphocyte counts less than 30. Sorting out these smoldering cases from MLUS and CLL is quite a problem.

At the moment it goes like this:

lymphocyte count less than 5K = MLUS (or (MBL) lymphocyte count 5-30K could be smoldering CLL (though 25% will eventually catch fire) lymphocyte count more than 30 = CLL.

Obviously, we don't like the label "leukemia" if patients don't have a malignant cancer but instead just have a benign tumor like a skin tag. I believe that judicious use of the prognostic markers would sort this out. In my own series patients with stage 0 CLL who have a lymphocyte count less than 30K and a CD38 of less than 30% have never died of CLL. Although a small percentage have had a little bit of treatment with Leukeran, they have remained responsive to this drug if it were ever needed again.

CD38 could easily be included in the normal immunophenotyping panel, and often is.