[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Risk factors associated with monoclonal B-cell lymphocytosis (MBL), a potential precursor of chronic lymphocytic leukaemia (CLL), remain unknown. METHODS: Using a cross-sectional study design, we investigated demographic, medical and behavioural risk factors associated with MBL. "Low-count" MBL (cases) were defined as individuals with very low median absolute count of clonal B-cells, identified from screening of healthy individuals and the remainder classified as controls. 452 individuals completed a questionnaire with their general practitioner, both blind to the MBL status of the subject. Odds ratios (OR) and 95% confidence interval (CI) for MBL were estimated by means of unconditional logistic regression adjusted for confounding factors. RESULTS: MBL were detected in 72/452 subjects (16%). Increasing age was strongly associated with MBL (P-trend<0.001). MBL was significantly less common among individuals vaccinated against pneumococcal or influenza (OR 0.49, 95% confidence interval (CI): 0.25 to 0.95; P-value = 0.03 and OR: 0.52, 95% CI: 0.29 to 0.93, P-value = 0.03, respectively). Albeit based on small numbers, cases were more likely to report infectious diseases among their children, respiratory disease among their siblings and personal history of pneumonia and meningitis. No other distinguishing epidemiological features were identified except for family history of cancer and an inverse relationship with diabetes treatment. All associations described above were retained after restricting the analysis to CLL-like MBL. CONCLUSION: Overall, these findings suggest that exposure to infectious agents leading to serious clinical manifestations in the patient or its surroundings may trigger immune events leading to MBL. This exploratory study provides initial insights and directions for future research related to MBL, a potential precursor of chronic lymphocytic leukaemia. Further work is warranted to confirm these findings.
PLoS ONE 12/2012; 7(12):e52808. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.Little is known about the distribution of normal lymphoid cells and their subsets in the peripheral blood (PB) of subjects with monoclonal B-cell lymphocytosis (MBL). In our study, we compared the absolute number of PB lymphoid cells and their subpopulations in 95 MBL cases with normal lymphocyte counts vs. 617 age-/sex-matched non-MBL healthy subjects (controls), using highly sensitive flow cytometry. MBL cases showed significantly reduced numbers of normal circulating B-cells, at the expense of immature and naive B-cells; in addition, CD4+CD8+ double-positive T-cells and CD8+ T-cells were significantly lower and higher vs. controls, respectively. Moreover, most normal B-cell subsets were significantly decreased in PB at >1% MBL-counts, vs. "low-count" MBL cases, and lower amounts of immature/naive B-cells were detected in biclonal (particularly in cases with coexisting CLL-like- and non-CLL-like B-cell clones) vs. monoclonal MBL subjects. In summary, our results show imbalanced (reduced) absolute numbers of recently produced normal circulating B-cells (e.g., immature and naıve B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.
American Journal of Hematology 03/2012; 87(7):721-4. · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) indicates <5 × 10(9) peripheral blood (PB) clonal B-cells/L in healthy individuals. In most cases, MBL cells show similar phenotypic/genetic features to chronic lymphocytic leukemia cells-CLL-like MBL-but little is known about non-CLL-like MBL.
PB samples from 639 healthy individuals (46% men/54% women) >40 years old (62 ± 13 years) with normal lymphocyte counts (2.1 ± 0.7 × 10(9)/L) were immunophenotyped using high-sensitive flow cytometry, based on 8-color stainings and the screening for >5 × 10(6) total PB leukocytes.
Thirteen subjects (2.0%; 9 males/4 females, aged 73 ± 10 years; absolute lymphocyte count: 2.4 ± 0.8 × 10(9)/L) showed a non-CLL-like clonal B-cell population, whose frequency clearly increased with age: 0.4%, 3%, and 5.4% of subjects aged 40-59, 60-79, and ≥80 years, respectively. One single B-cell clone was detected in 9/13 cases, while two B-cell clones were found in 4/13 (n = 17 MBL populations). Nine MBL cell populations showed a CD5(-) phenotype (usually overlapping with marginal zone-derived (MZL) or lymphoplasmacytic (LPL) non-Hodgkin lymphoma (NHL) B-cells, or an unclassifiable NHL), but CD5(-/+d) (n = 3) and CD5(+) (n = 3 non-CLL-like MBL, consistent with a mantle-cell lymphoma (MCL)-like phenotype, and n = 2 CLL-like) MBL were also identified; iFISH supported the diagnosis in most cases. No preferential IGHV usage of B-cell receptor could be found. Twelve cases reevaluated at month +12 showed circulating clonal B-cells, at mean levels significantly higher than those initially detected.
Non-CLL-like MBL cases frequently show biclonality, in association with MZL-, LPL-, MCL-like, or unclassifiable phenotypic profiles. As with CLL-like MBL, the frequency of non-CLL-like MBL increases with age, with a clear predominance of males.
Cytometry Part B Clinical Cytometry 01/2010; 78 Suppl 1:S24-34. · 2.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) indicates the presence of less than 5 x 10(9)/L circulating monoclonal B cells in otherwise healthy subjects. Recently, it has been reported that circulating chronic lymphocytic leukemia (CLL)-like B cells can be detected using 4- or 5-multicolor flow cytometry in 5% to 7% of adults with normal lymphocyte counts. We investigated the frequency of circulating monoclonal B cells in 608 healthy subjects older than 40 years with normal blood counts, using a highly sensitive 8-color flow cytometry approach and systematic screening for total PB leukocyte count higher than 5 x 10(6). We show that the frequency of PB monoclonal B cells is markedly higher than previously reported (12% for CLL-like B cells, found at frequencies of 0.17 +/- 0.13 x 10(9) cells/L), the incidence progressively increasing with age. Most cases (62%) showed clonal B-cell levels below the maximum sensitivity of the techniques described by others (< 0.01%), supporting the notion that detection of MBL may largely depend on the sensitivity of the flow cytometry approach used.