Clinico-Haematological Profile Of Chronic Lymphoproliferative Disorders In Patients Presenting With Lymphocytosis.

Objectives: To assess the spectrum and clinico-haematological profile of chronic lymphoproliferative disorders in patients presenting with lymphocytosis. METHODS: The cross-sectional, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data related to cases of bone marrow aspirate and trephine from January to November 2020. Patients for whom the bone marrow was done for lymphocytosis were studied for the presence of lymphoproliferative disorders, sub-types and patients'characteristics. The diagnosis and classification were based on the World Health Organisation criteria for tumours of haematopoietic and lymphoid tissues. Data was analysed using SPSS 21. RESULTS: Of the 3,334 bone marrow specimenstested, 103(3%) were related to lymphocytosis. Of these, 84(82%) were diagnosed with lymphoproliferative disorders, while diagnosisremained undetermined in 19(18%) cases. Male:female ratio was 3.6:1 and median age was 60 years (range: 21-85 years). Constitutional symptoms were found in 61(73%) patients. Median absolute lymphocyte count was 45x109/L (range: 5.3-480). All 84(100%) patients were classified as B-cell lymphoproliferative disorder. Chronic lymphocytic leukaemia wasthe most common form, 61(73%), and 31(51%) of them presented with advanced stage disease. CONCLUSIONS: A huge majority of patients presenting with lymphocytosis had underlying lymphoproliferative disorders of which B-cell chronic lymphocytic leukaemia was found to be the most common.

B-cell lymphocytosis in relatives of Colombian patients with chronic B-cell lymphoproliferative disorders / Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µl is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B.Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana.Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años.Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa.Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados,lo que sugiere que no existe afectación degenes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Bronchoalveolar lavage lymphocytosis in hypersensitivity pneumonitis: a retrospective cohort analysis with elimination of incorporation bias.

BACKGROUND: Recent studies support the diagnostic role of bronchoalveolar lavage lymphocytosis (BALL) in patients with suspected hypersensitivity pneumonitis (HP). Our study aim was to determine the spectrum of BALL findings with elimination of incorporation bias in non-fibrotic and fibrotic patients and assess correlates of positive BALL cut-off and BALL association with long-term outcomes in those with fibrotic disease (f-HP). METHODS: A single-center retrospective cohort study was pursued of patients undergoing diagnostic bronchoscopy for interstitial lung disease. Strict study enrollment was based on recent ATS/JRS/ALAT diagnostic guidance meeting 'moderate' or higher diagnostic confidence. BALL findings were assessed in both fibrotic and non-fibrotic HP patients with regression and survival analysis pursued for correlates of positive BALL cut-off and long-term outcome. RESULTS: A total of 148 patients (88 fibrotic and 60 non-fibrotic) meeting moderate or higher diagnostic confidence were included. Median BALL in f-HP was 15% compared to 19% in non-fibrotic patients, with only 28% of f-HP meeting diagnostic cut-off (≥ 30%) compared to 41% of non-fibrotic. For f-HP, centrilobular nodules on computed tomography was positively correlated with a diagnostic BALL (OR 4.07; p = 0.018) while honeycombing was negatively correlated (OR 6.9 × e-8; p = 0.001). Higher BALL was also associated with lower all-cause mortality (HR 0.98; p = 0.015). CONCLUSION: With elimination of incorporation bias, most patients with well-described HP did not meet diagnostic BALL thresholds. Higher BALL was associated with better long-term survival in those with fibrosis, but its diagnostic role may be more additive than characteristic or distinguishing.

Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans.

Monoclonal B-cell lymphocytosis (MBL) is a precursor to CLL. Other than age, sex, and CLL family-history, little is known about factors associated with MBL risk. A polygenic-risk-score (PRS) of 41 CLL-susceptibility variants has been found to be associated with CLL risk among individuals of European-ancestry(EA). Here, we evaluate these variants, the PRS, and environmental factors for MBL risk. We also evaluate these variants and the CLL-PRS among African-American (AA) and EA-CLL cases and controls. Our study included 560 EA MBLs, 869 CLLs (696 EA/173 AA), and 2866 controls (2631 EA/235 AA). We used logistic regression, adjusting for age and sex, to estimate odds ratios (OR) and 95% confidence intervals within each race. We found significant associations with MBL risk among 21 of 41 variants and with the CLL-PRS (OR = 1.86, P = 1.9 × 10-29, c-statistic = 0.72). Little evidence of any association between MBL risk and environmental factors was observed. We observed significant associations of the CLL-PRS with EA-CLL risk (OR = 2.53, P = 4.0 × 10-63, c-statistic = 0.77) and AA-CLL risk (OR = 1.76, P = 5.1 × 10-5, c-statistic = 0.62). Inherited genetic factors and not environmental are associated with MBL risk. In particular, the CLL-PRS is a strong predictor for both risk of MBL and EA-CLL, but less so for AA-CLL supporting the need for further work in this population.

Health impact of monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL): findings from a UK population-based cohort.

OBJECTIVE: To examine mortality and morbidity patterns before and after premalignancy diagnosis in individuals with monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL) and compare their secondary healthcare activity to that of the general population. DESIGN: Population-based patient cohort, within which each patient is matched at diagnosis to 10 age-matched and sex-matched individuals from the general population. Both cohorts are linked to nationwide information on deaths, cancer registrations and Hospital Episode Statistics. SETTING: The UK's Haematological Malignancy Research Network, which has a catchment population of around 4 million served by 14 hospitals and a central diagnostic laboratory. PARTICIPANTS: All patients newly diagnosed during 2009-2015 with MGUS (n=2193) or MBL (n=561) and their age and sex-matched comparators (n=27 538). MAIN OUTCOME MEASURES: Mortality and hospital inpatient and outpatient activity in the 5 years before and 3 years after diagnosis. RESULTS: Individuals with MGUS experienced excess morbidity in the 5 years before diagnosis and excess mortality and morbidity in the 3 years after diagnosis. Increased rate ratios (RRs) were evident for nearly all clinical specialties, the largest, both before and after diagnosis, being for nephrology (before RR=4.29, 95% CI 3.90 to 4.71; after RR=13.8, 95% CI 12.8 to 15.0) and rheumatology (before RR=3.40, 95% CI 3.18 to 3.63; after RR=5.44, 95% CI 5.08 to 5.83). Strong effects were also evident for endocrinology, neurology, dermatology and respiratory medicine. Conversely, only marginal increases in mortality and morbidity were evident for MBL. CONCLUSIONS: MGUS and MBL are generally considered to be relatively benign, since most individuals with monoclonal immunoglobulins never develop a B-cell malignancy or any other monoclonal protein-related organ/tissue-related disorder. Nonetheless, our findings offer strong support for the view that in some individuals, monoclonal gammopathy has the potential to cause systemic disease resulting in wide-ranging organ/tissue damage and excess mortality.

Clinical characteristics and mortality of patients with hematologic malignancies and COVID-19: a systematic review.

OBJECTIVE: Hematologic cancer patients with Coronavirus Disease 2019 (COVID-19) tend to have a more serious disease course than observed in the general population. Herein, we comprehensively reviewed existing literature and analyzed clinical characteristics and mortality of patients with hematologic malignancies and COVID-19. MATERIALS AND METHODS: Through searching PubMed until June 03, 2020, we identified 16 relevant case studies (33 cases) from a total of 45 studies that have reported on patients with COVID-19 and hematologic malignancies. We investigated the clinical and laboratory characteristics including type of hematologic malignancies, initial symptoms, laboratory findings, and clinical outcomes. Then, we compared those characteristics and outcomes of patients with hematologic malignancies and COVID-19 to the general population infected with COVID-19. RESULTS: The median age was 66-year-old. Chronic lymphocytic leukemia was the most common type of hematologic malignancy (39.4%). Fever was the most common symptom (75.9%). Most patients had normal leukocyte counts (55.6%), lymphocytosis (45.4%), and normal platelet counts (68.8%). In comparison to patients with COVID-19 without underlying hematologic malignancies, dyspnea was more prevalent (45.0 vs. 24.9%, p=0.025). Leukocytosis (38.9 vs. 9.8%, p=0.001), lymphocytosis (45.4 vs. 8.2%, p=0.001), and thrombocytopenia (31.3 vs. 11.4%, p=0.036) were significantly more prevalent and lymphopenia (18.2 vs. 57.4%, p=0.012) less prevalent in patients with hematologic malignancies. There were no clinical and laboratory characteristics predicting mortality in patients with hematologic malignancies. Mortality was much higher in patients with hematologic malignancies compared to those without this condition (40.0 vs. 3.6%, p<0.001). CONCLUSIONS: Co-occurrence of hematologic malignancies and COVID-19 is rare. However, due to the high mortality rate from COVID-19 in this vulnerable population, further investigation on tailored treatment and management is required.

Screening for monoclonal B-lymphocyte expansion in a hospital-based Chinese population with lymphocytosis: an observational cohort study.

OBJECTIVES: Screening of monoclonal B-cell lymphocytosis (MBL) has improved the early detection of B-cell lymphoproliferative disorders (B-LPDs). This study was designed to find the most cost-effective way to screen for asymptomatic B-LPD. DESIGN: Observational study. SETTING: A lymphocytosis screening project was conducted at a large-scale hospital among the Chinese population. PARTICIPANTS: For 10 consecutive working days in 2018, 22 809 adult patients who received a complete blood count (CBC) were reviewed. These patients were selected from the outpatient, inpatient and health examination departments of a National Medical Centre in China. RESULTS: A total of 254 patients (1.1%, 254/22 809) were found to have lymphocytosis (absolute lymphocyte count (ALC) >3.5×109/L). Among them, a population of circulating monoclonal B-lymphocytes were detected in 14 patients, with 4 having chronic lymphocytic leukaemia (CLL) and 10 having MBL, indicating an overall prevalence of 5.5% for B-LPD (3.9% for MBL). The prevalence of CLL among the elderly patients with lymphocytosis (≥60 years) was determined to be 4.3% (4/92). In the patients over 60 years of age, the prevalence of MBL was found to be 8.7%. CD5 (-) non-CLL-like MBL was observed to be the most common subtype (8, 80%), followed by CLL-like phenotype (1, 10.0%) and atypical CLL phenotype (1, 10.0%). The receiver operating characteristic curve analysis for the CBC results revealed that the ALC of 4.7×109/L may serve as the optimal and cost-effective cut-off for screening for early-stage asymptomatic B-LPD. CONCLUSION: In Chinese patients with lymphocytosis, there was a relatively high proportion of patients with CLL among individuals over 60 years of age. MBL is an age-related disorder. Non-CLL-like MBL was the most common MBL subtype, almost all of whom displayed a pattern of 'marginal zone lymphoma (MZL)-like' MBL. Lymphocytosis screening among the elderly would be effective in the detection of B-LPD and MBL.

PREVALENCE OF THROMBOCYTOSIS, THROMBOCYTOPENIA, LYMPHOCYTOSIS AND LYMPHOCYTOPENIA IN PATIENTS WITH LOWER RESPIRATORY TRACT INFECTION AND PATIENTS WITH URINARY TRACT INFECTION.

There are many reasons for abnormal lymphocyte and platelet counts. In this study, we aimed to assess the prevalence of thrombocytosis, thrombocytopenia, lymphocytosis and lymphocytopenia in patients with lower respiratory tract infection (LRTI) and patients with urinary tract infection (UTI). This retrospective study included 52 LRTI patients and 60 UTI patients. Control group consisted of 70 healthy individuals admitted to the infectiology outpatient unit. No statistically significant relationship was found between the groups of subjects and platelet count. Seven (11.7%) UTI patients and four (7.7%) LRTI patients had lymphocytopenia but there was no statistically significant relationship between the groups of subjects and lymphocyte count. Study results suggested a conclusion that lymphocyte and platelet counts could be within the normal ranges in patients with UTI, as well as in those with LRTI.

Prevalence and Immunophenotypic Characteristics of Monoclonal B-Cell Lymphocytosis in Healthy Korean Individuals With Lymphocytosis.

Epidemiological studies of monoclonal B-cell lymphocytosis (MBL) have been conducted in limited geographical regions. Little is known about the prevalence of MBL in Asia. We investigated the prevalence and immunophenotypic characteristics of MBL in Koreans who had idiopathic lymphocytosis (lymphocyte count >4.0×109/L) and were ≥40 years of age. A total of 105 leftover peripheral blood samples met these criteria among those from 73,727 healthy individuals who visited the Health Promotion Center, Samsung Medical Center, Korea, from June 2018 to August 2019. The samples were analyzed using eight-color flow cytometry with the following monoclonal antibodies: CD45, CD5, CD10, CD19, CD20, CD23, and kappa and lambda light chains. The overall prevalence of MBL in the study population was 2.9% (3/105); there was one case of chronic lymphocytic leukemia (CLL)-like MBL (CD5+CD23+), one case of atypical CLL-like MBL (CD5+CD23-), and one case of CD5-MBL with a lambda restriction pattern. This is the first study on the MBL prevalence in an East Asian population, and it reveals a relatively low prevalence of MBL in healthy Korean individuals with lymphocytosis.

Seasonal Variation of Duodenal Intraepithelial Lymphocytosis.

The increase of intraepithelial lymphocytes in architecturally normal duodenal mucosa is commonly referred to as duodenal intraepithelial lymphocytosis (DIL). The characteristic appearance of DIL corresponds with Marsh grade 1, that is, normal or mild increase in lamina propria inflammation of the duodenal mucosa, with no crypt hyperplasia or villous atrophy.1 Approximately 11% of DIL patients harbor clinical and serologic features suggestive of gluten sensitivity.2 An additional 2% of patients with DIL harbor concomitant microscopic colitis.3Helicobacter pylori gastritis may contribute to another 10%-15% of DIL, which may resolve following eradication of H pylori.4 In the majority of cases with DIL, however, its underlying cause has remained unknown.1 A study of the seasonal variations in the occurrence of DIL may provide additional clues about its yet unknown etiology.

Association of elevated serumfree light chains with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis.

Chronic lymphocytic leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL), are heritable. Serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but their role in susceptibility to CLL is not clear. We investigated differences between sFLC measurements in pre-treatment serum from five groups to inform the association of sFLC with familial and sporadic CLL: (1) familial CLL (n = 154), (2) sporadic CLL (n = 302), (3) familial MBL (n = 87), (4) unaffected first-degree relatives from CLL/MBL families (n = 263), and (5) reference population (n = 15,396). The percent of individuals having elevated monoclonal and polyclonal sFLCs was compared using age-stratified and age- and sex-adjusted logistic regression models. In age groups >50 years, monoclonal sFLC elevations were increased in sporadic and familial CLL cases compared to the reference population (p's < 0.05). However, there were no statistically significant differences in sFLC monoclonal or polyclonal elevations between familial and sporadic CLL cases (p's > 0.05). Unaffected relatives and MBL cases from CLL/MBL families, ages >60 years, showed elevated monoclonal sFLC, compared to the reference population (p's < 0.05). This is the first study to demonstrate monoclonal sFLC elevations in CLL cases compared to controls. Monoclonal sFLC levels may provide additional risk information in relatives of CLL probands.

Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population: a cross-sectional study.

BACKGROUND: Reported incidence of B-cell malignancies shows substantial geographical variation, being more common in the Americas and Europe than in Africa. This variation might reflect differences in diagnostic capability, inherited susceptibility, and infectious exposures. Monoclonal B-cell lymphocytosis (MBL) is a precursor lesion that can be screened for in apparently healthy people, allowing comparison of prevalence across different populations independently of health-care provision. We aimed to compare the prevalence and phenotypic characteristics of MBL in age-and-sex-matched populations from rural Uganda and the UK. METHODS: In this cross-sectional study, we recruited volunteers aged at least 45 years who were seronegative for HIV-1 from the established Ugandan General Population Cohort and obtained their whole-blood samples. We also obtained blood samples from anonymised waste material of age-and-sex-matched individuals (aged >45 years, with a normal blood count and no history of cancer) in the UK. We used flow cytometry to determine the presence of MBL, defined according to standard diagnostic criteria, in the samples and compared differences in the proportion of cases with chronic lymphocytic leukaemia (CLL)-phenotype MBL and CD5-negative MBL, as well as differences in absolute monoclonal B-cell count between the two cohorts. FINDINGS: Between Jan 15 and Dec 18, 2012, we obtained samples from 302 Ugandan volunteers and 302 UK individuals who were matched by age and sex to the Ugandan population. Overall MBL prevalence was higher in the Ugandan participants (42 [14%] individuals) than in the UK cohort (25 [8%]; p=0·038). CLL-phenotype MBL was detected in three (1%) Ugandan participants and 21 (7%) UK participants (p=0·00021); all three Ugandan participants had absolute monoclonal B-cell count below one cell per µL, whereas the 21 UK participants had a median absolute number of circulating neoplastic cells of 4·6 (IQR 2-12) cells per µL. The prevalence of CD5-negative MBL was higher in the Ugandan cohort (41 [14%], of whom two [5%] also had CLL-phenotype MBL) than in the UK cohort (six [2%], of whom two [33%] also had CLL-phenotype MBL; p<0·0001), but the median absolute B-cell count was similar (227 [IQR 152-345] cells per µL in the Ugandan cohort vs 135 [105-177] cells per µL in the UK cohort; p=0·13). INTERPRETATION: MBL is common in both Uganda and the UK, but the substantial phenotypic differences might reflect fundamental differences in the pathogenesis of B-cell lymphoproliferative disorders. FUNDING: UK Medical Research Council and UK Department for International Development.

Monoclonal Gammopathy of Undetermined Significance After Kidney Transplantation: Single-Center Experience.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder. Prevalence and clinical outcomes of MGUS in kidney transplant (KT) recipients have been previously reported in few studies with conflicting results. METHODS: We conducted a retrospective study in a population of 548 KT recipients transplanted between 1998 and 2015. RESULTS: Thirty-nine (8.1%) subjects developed MGUS after KT. At diagnosis of MGUS, the average age was 52 ± 9.2 years, and 23% of the patients were younger than 50 years. Occurrence of MGUS was not influenced by age and sex. After a mean follow-up of 7.8 years, only 1 (2.5%) patient progressed to multiple myeloma. We found no differences in the incidence of solid and hematological malignancies, serious infections, graft failure, and mortality between KT patients with MGUS and a matched cohort of KT recipients without MGUS. The MGUS group had a significantly higher prevalence of monoclonal B cell lymphocytosis, premalignant condition poorly described in KT recipients. Prior history of glomerulonephritis or interstitial nephritis, as cause of renal failure, represented the only predictive factor for MGUS development. CONCLUSIONS: MGUS is a premalignant disorder frequently encountered in KT recipients. We found no differences in clinical outcomes between MGUS patients and KT controls.

Lymphocytic Esophagitis: An Emerging Clinicopathologic Disease Associated with Dysphagia.

BACKGROUND: Lymphocytic esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. AIM: The aim of this study was to characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. METHODS: We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000, and June 1, 2012. Archived pathology slides were re-reviewed, and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. RESULTS: Twenty-seven adults were diagnosed with LyE, and the majority were female (63 %). The most common symptom was dysphagia (70 %). Fifty-two percentage had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37 %), erosive esophagitis (33 %), rings (26 %), and hiatal hernia (26 %); 33 % of patients required dilation. After histology re-review, 78 % of LyE patients were found to have more than 20 lymphs/hpf. In comparison with the normal, reflux and EoE controls, patients with LyE tended to be nonwhite (p < 0.01), were more commonly tobacco users (p = 0.02) and less likely to have seasonal allergies (p = 0.02). CONCLUSION: LyE commonly presents with dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE, whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy.

Monoclonal B-cell lymphocytosis in the population of Slovenian region of Lower Carniola.

INTRODUCTION: Monoclonal B-cell lymphocytosis (MBL) is a premalignant asymptomatic condition characterized by the presence of a small population of monoclonal B lymphocytes (less than 5 × 10(9) /L) in the venous blood of otherwise healthy individuals. Incidence of MBL is higher among first-degree relatives of patients with chronic lymphocytic leukemia (CLL) and also increases with age and among men. We compared the incidence of MBL found in the same environment in both an open general population and relatives of CLL patients. METHODS: Samples were analyzed with 5-parameter flow cytometry using following monoclonal antibodies: kappa and lambda clonality, CD5, CD19, CD20. We analyzed 216 samples of patients in the Slovenian area of Lower Carniola aged 23-88 years. Fifty-four patients who came from families where CLL is present were compared by age and gender to 162 healthy individuals from the general population of the same region. RESULTS: We found 10 cases of MBL (4.6%). In 9.4% of younger (≤ 50 years) first-degree relatives of CLL patients with immunophenotypic characteristics of atypical MBL, we observed a prevailingly normal κ to λ ratio. The difference in incidence of MBL cases between relatives and the general population decreases with age. CONCLUSION: MBL in Slovenia can be coincidentally found with a similar frequency to previously studied populations of other parts of Europe. We found, however, a higher incidence of atypical MBL among first-degree relatives.