Although these changes have anchored the diagnosis of CLL to clinical outcome, further investigation is needed to determine how best to distinguish between CLL and MBL. First, B-cell count appears to relate to TFS and OS as a continuous variable(19, 20) and recent studies suggest higher B-cell thresholds (e.g. 11 x 109/L) may not only stratify TFS but also predict OS.(20) Second, while these studies have demonstrated the ability of the B-cell count to stratify survival in patients with a clonal population of CLL phenotype, they have not benchmarked the outcome of these individuals to the general population. Conceptually, the expected survival of individuals with a precursor state to malignancy (e.g. adenomatous colon polyps) should be the same as that of the general population unless they go on to develop the at-risk disease (e.g. colon cancer). While B-cell count is clearly established as a prognostic factor in patients with MBL, whether or not it can be used to identify those individuals with a circulating B-cell clone whose OS is shorter than unaffected individuals in the general population has not yet
