Definitions of MBL and CLL
Monoclonal B-cell Lymphocytosis (MBL) is a preclinical condition characterized by fewer than 5,000 clonal B cells/mcL in peripheral blood without lymphadenopathy, organomegaly, or cytopenias, while Chronic Lymphocytic Leukemia (CLL) requires at least 5,000 monoclonal B lymphocytes/mcL in peripheral blood confirmed by flow cytometry. 1
Monoclonal B-cell Lymphocytosis (MBL)
Diagnostic Criteria
- MBL is defined by an absolute monoclonal B-cell count <5 × 10⁹/L in peripheral blood with no palpable lymphadenopathy (lymph nodes <1.5 cm), no thrombocytopenia or anemia, and no constitutional symptoms 1, 2
- Diagnosis requires flow cytometry demonstrating light chain restriction (kappa or lambda) and a typical immunophenotype: CD5+, CD19+, CD20 dim, CD23+, with low surface immunoglobulin expression 2
Subtypes and Risk Stratification
- Low-count MBL: <0.5 × 10⁹/L B-cells, detected in approximately 5% of adults over age 40 using standard flow cytometry 3
- High-count MBL: ≥0.5 × 10⁹/L B-cells but <5 × 10⁹/L, which progresses to CLL requiring therapy at a rate of 1-2% per year 3
- Low-count MBL rarely progresses to CLL, whereas high-count MBL carries greater progression risk 3
Molecular Characteristics
- MBL typically exhibits favorable molecular features including mutated immunoglobulin heavy-chain variable region gene (IGHV) and chromosomal abnormality del(13q) or normal cytogenetics 1
- Some low-count MBL cases are oligoclonal rather than monoclonal, with 87% having mutated immunoglobulin genes 4
Clinical Significance
- The estimated rate of progression from MBL to CLL is 1.1% per year overall 1
- MBL is not leukemia or lymphoma—it represents a preclinical condition that most commonly remains stable 2
- Observation with complete blood counts every 3-12 months is recommended for all individuals with MBL 1, 2
Chronic Lymphocytic Leukemia (CLL)
Diagnostic Criteria
- CLL requires the presence of at least 5,000 monoclonal B lymphocytes/mcL (5 × 10⁹/L) in peripheral blood, with clonality confirmed by flow cytometry 1
- Flow cytometry of peripheral blood alone is adequate for CLL diagnosis without requiring biopsy 5
- The characteristic immunophenotype includes: CD5+, CD10−, CD19+, CD20 dim, surface immunoglobulin dim, CD23+, CD43+/−, cyclin D1− 5
Clinical Characteristics
- CLL is the most prevalent adult leukemia in Western countries, constituting approximately 7% of newly diagnosed non-Hodgkin's lymphoma cases 1
- Morphologically, leukemic cells appear as small, mature lymphocytes that may be admixed with occasional larger atypical cells or prolymphocytes 1
- CLL is characterized by progressive accumulation of leukemic cells in peripheral blood, bone marrow, and lymphoid tissues 1
Relationship to Small Lymphocytic Lymphoma (SLL)
- CLL and SLL are different manifestations of the same disease and are managed similarly 1
- The major difference: in CLL, abnormal lymphocytes are found significantly in bone marrow and blood, while in SLL they are predominantly in lymph nodes and bone marrow 1
- SLL diagnosis requires lymphadenopathy and/or splenomegaly with less than 5,000 B lymphocytes/mcL in peripheral blood 1
Epidemiology
- In 2015, an estimated 14,620 people were diagnosed with CLL in the United States, with an estimated 4,650 deaths from the disease 1
- CLL is considered rare in regions such as East Asia 1
Key Distinction Between MBL and CLL
The critical threshold is 5,000 monoclonal B cells/mcL (5 × 10⁹/L): below this level without other features defines MBL, while at or above this level defines CLL 1. High-count MBL (≥0.5 × 10⁹/L but <5 × 10⁹/L) is distinguished from Rai 0 CLL based solely on whether the B-cell count is above or below this 5 × 10⁹/L threshold 3.