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Lymphoma-like monoclonal B cell lymphocytosis in a patient population: biology, natural evolution, and differences from CLL-like clones

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Abstract

High-count monoclonal B cell lymphocytosis (MBL) with a chronic lymphocytic leukemia (CLL) phenotype is a well-known entity, featuring 1–4% annual risk of progression towards CLL requiring treatment. Lymphoma-like MBL (L-MBL), on the other hand, remains poorly defined and data regarding outcome are lacking. We retrospectively evaluated 33 L-MBL cases within our hospital population and compared them to 95 subjects with CLL-like MBL (C-MBL). Diagnoses of L-MBL were based on asymptomatic B cell clones with Matutes score < 3, B cells < 5.0 × 103/μl, and negative computerized tomography scans. We found that median B cell counts were considerably lower compared to C-MBL (0.6 vs 2.3 × 103/μl) and remained stable over time. Based on immunophenotyping and immunogenetic profiling, most L-MBL clones did not correspond to known lymphoma entities. A strikingly high occurrence of paraproteinemia (48%), hypogammaglobulinemia (45%), and biclonality (21%) was seen; these incidences being significantly higher than in C-MBL (17, 21, and 5%, respectively). Unrelated monoclonal gammopathy of undetermined significance was a frequent feature, as the light chain type of 5/12 paraproteins detected was different from the clonal surface immunoglobulin. After 46-month median follow-up, 2/24 patients (8%) had progressed towards indolent lymphoma requiring no treatment. In contrast, 41% of C-MBL cases evolved to CLL and 17% required treatment. We conclude that clinical L-MBL is characterized by pronounced immune dysregulation and very slow or absent progression, clearly separating it from its CLL-like counterpart.

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Authors and Affiliations

  1. Department of Clinical Biology, Hematology Division, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium

    Sam Vander Meeren, Wim Renmans, Marleen Bakkus & Kristin Jochmans

  2. Department of Internal Medicine, Hematology Division, ZNA Middelheim, Antwerpen, Belgium

    Bert Heyrman

  3. Department of Clinical Biology, Hematology Division, Jessa Ziekenhuis, Hasselt, Belgium

    Brigitte Maes

  4. Department of Pathology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium

    Hendrik De Raeve

  5. Department of Internal Medicine, Hematology Division, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium

    Rik Schots

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  1. Sam Vander Meeren
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Contributions

SVM and KJ designed the study. SVM analyzed the data and wrote the paper. BH and RS performed diagnoses. WR performed immunophenotyping analyses. MB and BM were responsible for molecular data analysis and HDR for interpretation of pathologic findings. KJ supervised the study. BH, WR, MB, BM, HDR, RS, and KJ reviewed drafts of the paper and approved the final version.

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Correspondence to Sam Vander Meeren.

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The study was approved by the Ethics Committee of the University of Brussels.

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The authors declare that they have no conflict of interest.

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Vander Meeren, S., Heyrman, B., Renmans, W. et al. Lymphoma-like monoclonal B cell lymphocytosis in a patient population: biology, natural evolution, and differences from CLL-like clones. Ann Hematol 97, 1219–1227 (2018). https://doi.org/10.1007/s00277-018-3282-0

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