What percentage of monoclonal B-cell lymphocytosis (MBL) progresses to Chronic Lymphocytic Leukemia (CLL)?

From the Guidelines

Approximately 1-2% of individuals with monoclonal B-cell lymphocytosis (MBL) progress to chronic lymphocytic leukemia (CLL) per year. This progression rate applies specifically to clinical MBL, which is characterized by a B-cell count greater than 500 cells/μL but less than the 5000 cells/μL threshold used to diagnose CLL, as stated in the guidelines by 1. The risk of progression is influenced by several factors, including the absolute B-cell count (with higher counts associated with increased risk), specific genetic abnormalities (particularly del(17p), del(11q), and complex karyotype), and the presence of unmutated IGHV genes.

Some key points to consider in the management of MBL include:

• The distinction between low-count MBL (<0.5 x 10^9/L) and high-count MBL (>0.5 x 10^9/L), with the latter being more likely to progress to CLL, as noted in 1 and 1.
• The importance of regular monitoring with complete blood counts and clinical evaluations to allow for early detection of progression to CLL.
• The fact that most individuals with MBL will never progress to requiring treatment for CLL in their lifetime, and many will die from unrelated causes, highlighting the need for a balanced approach to management that takes into account the individual's overall health and risk factors.

It's worth noting that the evidence from 1, 1, and 1 all supports the idea that MBL is a precursor condition to CLL, and that regular monitoring is essential for early detection and management of progression. However, the most recent and highest quality study, 1, provides the most up-to-date guidance on the management of MBL and the risk of progression to CLL.

From the Research

Monoclonal B-cell Lymphocytosis (MBL) Progression to Chronic Lymphocytic Leukemia (CLL)

• The progression rate of MBL to CLL varies, with high-count MBL progressing to CLL requiring therapy at a rate of 1% to 2% per year 2, 3, 4, 5.
• Low-count MBL rarely progresses to CLL, with an exceedingly small risk of progression 2, 4.
• A study published in 2024 found that MBL progresses to CLL requiring therapy at 1% to 5% per year, and identified an epigenetic and immunogenetic signature that can predict outcomes for high-count MBL 6.
• The absolute B-cell count is most strongly associated with progression, and patients with low-count MBL identified in population screening studies rarely develop CLL 5.
• High-count MBL is distinguished from Rai 0 CLL based on whether the B-cell count is above or below 5 × 10(9)/L, and individuals with high-count MBL are at increased risk of infections and second cancers 2.

Risk Stratification

• MBL can be categorized as either low-count or high-count based on whether the B-cell count is above or below 0.5 × 10(9)/L 2, 3, 4.
• High-count MBL carries a higher risk of progression to CLL requiring therapy, as well as a higher risk of infectious complications and secondary malignancies 2, 3, 4.
• The ELCLV3-21 signature can classify individuals with MBL into high-risk and low-risk groups, with high-risk individuals having a higher probability of progression to CLL 6.

Clinical Management

• Individuals with low-count MBL do not require any specific follow-up, while those with high-count MBL should be monitored at least annually for progressive lymphocytosis and signs or symptoms of CLL 4, 5.
• The appropriate management of MBL individuals should take into account the risk of developing infections, other cancers, and autoimmune disorders 3.