Monoclonal B-Cell Lymphocytosis

Date of document February 2012
This document is not the most recent version. Please view: Monoklonale B-Zell Lymphozytose

1Definition and Basic Information

Monoclonal B-cell lymphocytosis (MBL) is defined by the presence of a monoclonal B-cell population in the peripheral blood, with [2]:

  • light-chain restriction (kappa:lambda of <3:1 or <0.3:1), or

  • monoclonal immunoglobulin heavy-chain gene rearrangement, or

  • 25% B cells with low or absent expression of surface immunoglobulins, or

  • B-cell population with an aberrant immunophenotype.

These findings must be reproducible and stable for at least 3 months.

However, MBL is ruled out by the following criteria:

  • lymphadenopathy or organomegaly, or

  • associated autoimmune disease (e.g. AIHA) or infectious complications, or

  • B lymphocytes >5 G/l in the peripheral blood, or

  • any other feature of manifested lymphoproliferative neoplasm.

In 80% of the cases MBL displays a CLL phenotype ("CLL-like MBL": light-chain restriction, CD5+/CD19+/CD20low/CD23+/Iglow). The two most deviating phenotypes are MBL with the atypical CLL phenotype (light-chain restriction, CD5+/CD19+/ CD20+/CD23+/Ig+ or CD5+/CD19+/ CD20low/CD23-/ Ig+) and MBL with the non-CLL phenotype (light-chain restriction, CD5-/CD19+/CD20+/ Ig+) [3].

2Incidence Rate

MBL is detectable in the general population at a rate of approx. 0.5-5% [4]. Prevalence depends on the diagnostic method and the age of the patient. It increases with increasing age and is also markedly higher in groups of first-degree relatives with a history of manifest lymphoproliferative disease.

3Risk of Progression

The risk of MBL transforming into a therapy requiring CLL or any other malignant lymphoma amounts to rate of approx. 1-2% per year [7]. Epidemiological studies confirm individual variations in the likelihood of progression [56]. Seminal studies on the other hand, demonstrated that almost every CLL is preceded by MBL [1].

Parameters of progression in CLL patients are not applicable for a reliable estimation of the likelihood of progression of a "CLL-type MBL". It can merely be stated that the prevalence of CLL-typical cytogenetic (e.g. del(13q)) or molecular genetic lesions (e.g. IgHV mutation status) increases with increasing lymphocyte counts [48]. Despite the fact that larger studies on this subject are still unavailable a monoclonal B-cell lymphocytosis of ≥1.9 G/l may be currently regarded as a practically relevant threshold limit value (see below).


The diagnosis of MBL is often incidental. However, if there are specific suspicious facts which indicate a lymphoproliferative disease, particularly a persisting lymphocytosis, the diagnosis of MBL usually results from the according diagnostics by exclusion. A diagnostic algorithm is presented in the overview below, see Figure 1.

Figure 1: Differential Diagnostics of B-Cell Lymphocytosis 
Differential Diagnostics of B-Cell Lymphocytosis
1 NHL-typical symptoms: B symptoms (fever, night sweats, weight loss), autoimmune cytopenias, opportunistic infections2  The aleukemic form of CLL is classified as small-cell lymphocytic lymphoma (SLL).


The objects pursued by follow-up examinations consist first of all in the exclusion of a treatment requiring lymphoproliferative disease at an early stage, and the as early as possible identification of a development which is directed toward a prognostically unfavorable or treatment requiring disease.

As 90% of the individuals who have MBL and a stable lymphocytosis of <1.9 G/l do not display progression over a period of five years, a single follow-up examination appears to be sufficient for this group, by means of immunophenotyping 6-12 months after the initial diagnosis [5], see Tab 1.

Individuals with a lymphocytosis of ≥1.9 G/l display a high risk of progression, wherefore regular examinations in intervals of 6-12 months appear to be indicated for this group. In addition to immunophenotyping, a physical examination should also proceed in these cases, perhaps supplemented by sonography of the abdomen inclusive of lymph-node sonography, in order to identify a lymphadenopathy or organomegaly [5].





Initial diagnosis



Immunophenotyping, clinical examination


< 1.9 G B cells

once after 6-12 months

Differential blood cell count, perhaps immunophenotyping

≥ 1.9 G/l B cells

regularly, every 6-12 months

Differential blood cell count, perhaps immunophenotyping, clinical examination

In case the number of B cells exceeds a value of ≥5.0 G/l, or should symptoms typical of a lymphoma appear additionally (e.g. lymphadenopathy, splenomegaly, autoimmune cytopenia), a manifest lymphoproliferative disease (CLL etc.) will have to be diagnosed. See elsewhere other Onkopedia Guidelines for further diagnostics.

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  1. Landgren O, Albitar M, Ma W et al. B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med 360:659-667, 2009. PMID:19213679

  2. Marti GE, Rawstron AC, Ghia P et al. Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol 130:325-332, 2005. DOI:10.1111/j.1365-2141.2005.05550.x

  3. Mulligan CS, Thomas ME, Mulligan SP. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008;359:2065-2066, 2008. PMID:18987375

  4. Rawstron AC, Bennett FL, O'Connor SJ et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med 359:575-583, 2008. PMID:18687638

  5. Rawstron AC. Monoclonal B-cell lymphocytosis. Hematology Am Soc Hematol Educ Program 430-439, 2009. PMID:20008229

  6. Rossi D, Sozzi E, Puma A et al. The prognosis of clinical monoclonal B cell lymphocytosis differs from prognosis of Rai 0 chronic lymphocytic leukaemia and is recapitulated by biological risk factors. Br J Haematol 146:64-675, 2009. DOI:10.1111/j.1365-2141.2009.07711.x

  7. Shanafelt TD, Ghia P, Lanasa MC et al. Monoclonal B-cell lymphocytosis (MBL): biology, natural history and clinical management. Leukemia 24:512-520, 2010. DOI:10.1038/leu.2009.287

  8. Shanafelt TD, Kay NE, Rabe KG et al. Brief report: natural history of individuals with clinically recognized monoclonal B-cell lymphocytosis compared with patients with Rai 0 chronic lymphocytic leukemia. J Clin Oncol 27:3959-3963, 2009. DOI:10.1200/JCO.2008.21.2704

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16Authors’ Affiliations

Prof. Dr. med. Monika Brüggemann
Universitätsklinikum Schleswig-Holstein
Klinik für Innere Medizin II
Hämatologie und Onkologie
Langer Segen 8-10
24105 Kiel
Ao. Univ. Prof. Dr. Alexander Egle
Landeskrankenhaus Salzburg
3. Med. Universitätsklinik für Hämatologie
Müllnerhauptstr. 48
A-5020 Salzburg
Dr. med. Michael Gregor
Luzerner Kantonsspital
Departement Medizin
Hämatologische Abteilung
CH-6000 Luzern 16
Prof. Dr. med. Karl-Anton Kreuzer
Klinikum der Universität zu Köln
Klink I für Innere Medizin
Kerpener Str. 62
50937 Köln
Prof. Dr. med. Clemens-Martin Wendtner
Klinik für Hämatologie, Onkologie, Immunologie,
Palliativmedizin, Infektiologie und Tropenmedizin
München Klinik Schwabing
Kölner Platz 1
80804 München

17Disclosure of Potential Conflicts of Interest

according to the rules of the responsible Medical Societies.




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