The earliest population studies were performed in the U.S. in the 1990s as part of a larger investigation into the potential health impact of living around hazardous waste sites.(2) These studies included an immune biomarker panel with basic lymphocyte immunophenotyping but not B-cell kappa:lambda analysis. As discussed in the introduction, the overall prevalence from the initial study and two follow-up analyses using this approach was 9/1499 (0.6%) individuals.(3) Later studies performed independently in the UK and Italy assessed the prevalence of clonal B-cells in individuals with normal blood counts using four-color flow cytometry with a sensitivity of detection commonly used for detection of minimal residual disease in patients with CLL (1 clonal cell per 1 x 105 events).(7) These studies demonstrated a much higher prevalence of CLL-like MBL which was detected in more than 5% of adults aged over 60.(4, 5) The UK study(4) involved hospital outpatients with no history or suspicion of cancer and the Italian study(5) involved individuals from a rural community referred for routine blood tests (e.g. blood glucose, blood lipids). CLL-phenotype cells in these patients typically
