Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: diagnosis, natural history, and risk stratification

Abstract

Monoclonal B 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. The majority of cases of MBL have the immunophenotype of chronic lymphocytic leukemia (CLL). 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. Low-count MBL can be detected in ∼5% of adults over the age of 40 years when assessed using standard-sensitivity flow cytometry assays. A number of biological and genetic characteristics distinguish low-count from high-count MBL. Whereas low-count MBL rarely progresses to CLL, high-count MBL progresses 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 the B-cell count is above or below 5 × 10(9)/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 review highlights challenging questions regarding the classification, risk stratification, management, and supportive care of patients with MBL and CLL.

Figure 1

General approach to the workup of lymphocytosis. BM, bone marrow; CMV, cytomegalovirus; CTD, connective tissue disease; EBV, Epstein-Barr virus; FL, follicular lymphoma; HCL, hairy cell leukemia; HTLV, human T-lymphotropic virus; LGL, large-granular leukemia; LN, lymph nodes; LPL, lymphoplasmacytic lymphoma; MCL, mantle cell lymphoma; MF, mycosis fungoides; T-PLP, T prolymphocytic leukemia; SMZ, splenic marginal zone lymphoma; T-leu, T-cell leukemia; VZV, varicella zoster virus.

Figure 2

Distribution of clonal CLL-like B-cell count in published studies. Two main entities can be identified: low-count MBL, usually detected in general population studies, and high-count MBL, usually detected in series of patients referred for lymphocytosis. Reprinted with permission from Rawstron et al.

Figure 3

Management of early-stage CLL and SLL. B2M, β-2-microglobulin; IgG, immunoglobulin G; IVIG, intravenous immunoglobulins; MX, mammogram; PCV, pneumococcus vaccine; PS, performance status; Tdap, tetanus diphtheria, acellular pertussis.