What is the diagnosis of Monoclonal B-cell Lymphocytosis (MBL)?

From the Guidelines

Monoclonal B-cell lymphocytosis (MBL) is diagnosed when an absolute monoclonal B-lymphocyte count of <0.5 x 10^9/L is stable over a 3-month period in the absence of palpable lymphadenopathy or other clinical features characteristic of a lymphoproliferative disorder. Diagnosis of MBL requires flow cytometry analysis of peripheral blood to identify the abnormal B-cell clone, typically showing CD5+, CD19+, and CD23+ expression with dim surface immunoglobulin (often with kappa light chain restriction) in CLL-like MBL 1. A complete blood count with differential, peripheral blood smear examination, and comprehensive metabolic panel should be performed. Bone marrow examination is not routinely required unless there are concerning features. MBL is further categorized into low-count MBL (<0.5 x 10^9/L) that rarely progresses to CLL and high-count MBL (>0.5 x 10^9/L) that progresses to CLL requiring treatment 1.

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

• The presence of an abnormal B-cell population with the immunophenotype of CLL but not meeting the diagnostic criteria for CLL 1
• The estimated rate of progression of MBL to CLL is 1.1% per year 1
• Favorable molecular lesions, such as mutated immunoglobulin heavy-chain variable region gene (IGHV) and chromosomal abnormality del(13q) or normal cytogenetics, are commonly seen in individuals with MBL 1
• The distinction between MBL and CLL is important as it guides management decisions, with MBL representing a precursor state that may remain stable for years or decades in most patients 1

Low-count MBL (<0.5 x 10^9/L clonal B-cells) generally requires no treatment and only periodic monitoring with annual complete blood counts, while high-count MBL (0.5-5.0 x 10^9/L) warrants closer follow-up every 6-12 months due to its 1-2% annual risk of progression to chronic lymphocytic leukemia (CLL) 1.

From the Research

Definition and Diagnosis of Monoclonal B-cell Lymphocytosis

• Monoclonal B-cell lymphocytosis (MBL) is defined as the presence of a clonal B-cell population in the peripheral blood with fewer than 5 × 10(9)/L B-cells and no other signs of a lymphoproliferative disorder 2, 3, 4, 5, 6.
• 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.
• The majority of cases of MBL have the immunophenotype of chronic lymphocytic leukemia (CLL) 2, 3, 4, 5, 6.

Risk Stratification and Progression

• Low-count MBL rarely progresses to CLL, whereas high-count MBL progresses to CLL requiring therapy at a rate of 1% to 2% per year 2, 3, 5, 6.
• High-count MBL is distinguished from Rai 0 CLL based on whether the B-cell count is above or below 5 × 10(9)/L 2.
• Individuals with high-count MBL are at increased risk of infections and second cancers, and the risk of progression requiring treatment and the potential to shorten life expectancy are greater for CLL 2, 3.

Biological and Genetic Characteristics

• MBL can be characterized by cytogenetic and molecular analyses, including the detection of chromosomal abnormalities such as 13q14 deletion and trisomy 12 5.
• The immunoglobulin heavy variable group (IGHV) genes repertoire is skewed in CLL-phenotype MBL, similar to CLL 5.
• Immunogenetic, cytogenetic, and genetic data support the notion that high-count MBL is a premalignant condition 4.