Diagnostic criteria for monoclonal B‐cell lymphocytosis

Abstract

SummaryVery low levels of circulating monoclonal B‐cell subpopulations can now be detected in apparently healthy individuals using flow cytometry. We propose the term ‘monoclonal B‐cell lymphocytosis’ (MBL) to describe this finding. The aim of this document is to provide a working definition of MBL for future clinical, epidemiological and laboratory studies. We propose that the detection of a monoclonal B‐cell population by light chain restriction is sufficient to define this condition in individuals not meeting the diagnostic criteria for other B‐lymphoproliferative disorders. The majority of individuals with MBL will have cells that are indistinguishable from chronic lymphocytic leukaemia (CLL). However, this blood cell clonal expansion of CD5+ or CD5− B‐lymphocytes is age‐dependent and immunophenotypic heterogeneity is common. Longitudinal studies are required to determine whether MBL is a precursor state to CLL or other B‐lymphoproliferative disease in a situation analogous to a monoclonal gammopathy of undetermined significance and myeloma. Future studies of MBL should be directed towards determining its relationship to clinical disease, particularly in individuals from families with a genetic predisposition to developing CLL.

Monoclonal B‐cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B‐cell subsets

“…Follicular lymphoma (FL) is one of the most common subtypes of NHL, with over 24,000 new cases diagnosed each year in the United States [1,2]. Prior to the rituximab era, FL had a median survival of 10 years, but progression varied and survival ranged from <1 year to >20 years after diagnosis [3].…”

“…The Follicular Lymphoma International Prognostic Index (FLIPI) separates FL patients into three risk groups based on age, stage of disease, concentrations of b2-microglobulin and hemoglobin, nodal area involvement, serum lactate dehydrogenase levels, and bone marrow involvement [5,6]. Treatment strategies for FL have included ''watchful waiting,'' chemotherapy, immunochemotherapy, radiotherapy, radioimmunoconjugates, and stem cell transplantation [1]. Although new treatment strategies have changed the survival of patients with FL, patients continue to die from disease or complications of survival from disease [7].…”

“…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/naïve 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 naïve B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.The revised National Cancer Institute Working Group/International Workshop on chronic lymphocytic leukemia (CLL) recognized monoclonal B-cell lymphocytosis (MBL) as a new diagnostic category defined by presence of <5 3 10 9 /L circulating monoclonal B-cells -most frequently resembling the phenotype and genetic features of CLL cells-in otherwise healthy subjects [1][2][3][4]. It has been suggested that the clinical significance of MBL is different depending on whether a given MBL is identified during the diagnostic evaluation of a lymphocytosis or through screening procedures of subjects with normal lymphocyte counts [3]; accordingly, the probability of MBL to progress to CLL increases among cases showing higher B-cell numbers [3,[5][6][7][8][9][10][11][12][13].…”

MBL or CLL: Which classification best categorizes the clinical course of patients with an absolute lymphocyte count ≥5×109L−1 but a B-cell lymphocyte count <5×109L−1?

“…blood, a B lymphocyte count <5.0 × 10 9 /L, and the absence of lymphadenopathy, organomegaly, or autoimmune/infectious disease as having MBL 4 . These criteria could cause confusion in patient classification as the diagnosis of CLL by the NCI 1996 criteria 1 is based on the ALC (an aggregate lymphocyte measure comprised of B cells, T cells, and NK cells) 1 whereas the diagnosis of MBL is based on the B lymphocyte count 4 .…”

Nodal and leukemic small B-cell neoplasms

“…37 Approximately 1-2% of MBL patients per year progress to CLL, although many MBL patients never require therapy. 51,52 It should be noted, however, that this cutoff was chosen in a rather arbitrary fashion, and recent studies have attempted to define a biological cutoff threshold based on time to first therapy requirements. These studies have generally suggested that a higher cutoff, perhaps as high as 10-11 Â 10 9 , may be more useful for the distinction between MBL and CLL.…”