Clinical, Phenotypic, and Genetic Characteristics of Non-CLL Type Monoclonal B Lymphocytosis (MBL)

Abstract 5209

Monoclonal B-cell lymphocytosis (MBL) has been established as a diagnostic category to denote the finding of clonal B lymphocytes in otherwise healthy and asymptomatic individuals. MBL likely represents early lesions in lymphoid neoplasms. Immunophenotypically, MBL is divided into CD5+ CLL-type and CD5- non-CLL type MBL, respectively. While most studies have focused on CLL-type MBL and provided evidence of progression of MBL to clinical CLL, the biological nature and clinical relevance of non-CLL type MBL remain unclear. In this study, we have identified and evaluated a series of 18 patients with non-CLL type MBL. This group comprised 10 males and 8 females with a median age of 74 years (range 53–95). All the patients presented initially with a mild to moderate absolute lymphocytosis. Clinical and laboratory evaluations were performed with a follow-up period of 1–20 years (median 8.5). Clonal B lymphocyte populations were confirmed by flow cytometry analysis. All the MBL clones showed negative for CD5, CD10 and CD103, positive for CD19 and CD20, and heterogeneous for CD23, CD25, CD79b, FMC7 and CD38. The phenotypic findings excluded CLL, mantle cell lymphoma and hairy cell leukemia, but may overlap with marginal zone lymphoma or lymphoplasmacytic lymphoma. Cytogenetics were available for 9 patients. Of the cytogenetic abnormalities, 7q deletion was found in two clones, 17 q deletion in two other clones, 11q deletion in one clone and t(2;7) in another clone. An overall tendency was shown toward clonal expansion with an increase in absolute lymphocyte count (ALC) over time (initial mean ALC of 4.9 ± 0.46 × 10⁹/L to a recent mean ALC of 8.3 ± 2.18 × 10⁹/L, p = 0.151). Three patients had an initial ALC >8 × 10⁹/L which remained stable in one patient and decreased to <6 × 10⁹/L in 2 patients. The patient with the longest follow-up of 20 years underwent a completely benign course, while the CD5- clonal B cell population was persistent but non-progressing. Of the progressive clones, three patients had an increase in ALC >10 × 10⁹/L; one patient's ALC progressed over a period of 9 years to 35 × 10⁹/L that required treatment. Clinically, three patients developed splenomegaly and one patient progressed with lymphadenopathy. Unlike the findings from population screening, this study represents a series of clinical MBL of non-CLL phenotype, and our results indicate the heterogeneity in genetic changes and clonal progression.