Review Series CHRONIC LYMPHOCYTIC LEUKEMIA: TAKING A BIG LEAP FORWARD Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: diagnosis, natural history, and risk stratification

Monoclonal B lymphocytosis (MBL) is de-fined as the presence of a clonal B-cell population in the peripheral blood with fewer than 5 3 109/L B-cells and no other signs of a lymphoproliferative disorder. The majority of cases of MBL have the immunophenotype of chronic lympho-cytic leukemia (CLL). MBL can be catego-rized as either low count or high count based on whether the B-cell count is above or below 0.5 3 109/L. Low-count MBLcanbedetected in∼5%of adultsover the age of 40 years when assessed using standard-sensitivity flowcytometryassays. A number of biological and genetic charac-teristics distinguish low-count from high-count MBL. Whereas low-count MBL rarely progresses to CLL, high-count MBL pro-gresses to CLL requiring therapy at a rate of 1 % to 2 % per year. High-count MBL is distinguished from Rai 0 CLL based on whether theB-cell count is aboveor below 5 3 109/L. Although individuals with both high-count MBL and CLL Rai stage 0 are at increased risk of infections and second cancers, the risk of progression requiring treatment and the potential to shorten life expectancy are greater for CLL. This re-view highlights challenging questions regarding the classification, risk stratifi-cation, management, and supportive care of patients with MBL and CLL. (Blood. 2015;126(4):454-462