Diagnostic criteria for monoclonal B‐cell lymphocytosis

Very 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.

[1]  R. Houlston,et al.  Inherited predisposition to CLL is detectable as subclinical monoclonal B-lymphocyte expansion. , 2002, Blood.

[2]  G. Morgan,et al.  Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. , 2001, Blood.

[3]  Michael J. Green,et al.  Monoclonal B lymphocytes with the characteristics of "indolent" chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts. , 2002, Blood.

[4]  Terry M Therneau,et al.  A long-term study of prognosis in monoclonal gammopathy of undetermined significance. , 2002, The New England journal of medicine.

[5]  E. Kimby,et al.  Clonal cell surface structures related to differentiation, activation and homing in B‐cell chronic lymphocytic leukemia and monoclonal lymphocytosis of undetermined significance , 1989, European journal of haematology.

[6]  G. Marti,et al.  CD20 and CD5 Expression in B‐Chronic Lymphocytic Leukemia , 1992, Annals of the New York Academy of Sciences.

[7]  J. Byrd.  Clonal lymphocytosis of uncertain significance (CLUS): what clues will CLUS yield? , 2002 .

[8]  R. Kyle,et al.  Monoclonal gammopathies of undetermined significance. , 2002, Reviews in clinical and experimental hematology.

[9]  Chen Wang,et al.  Differentiation of monoclonal B lymphocytosis of undetermined significance (MLUS) and chronic lymphocytic leukemia (CLL) with weak CD5 expression from CD5(-) CLL. , 2002, Leukemia research.

[10]  M. Potter,et al.  Mechanisms of B cell neoplasia 1991 : workshop at the Basel Institute for Immunology, April 14-16, 1991 , 1991 .

[11]  Douglas A. Hosack,et al.  Telomere length and heavy-chain mutation status in familial chronic lymphocytic leukemia. , 2002, Leukemia research.

[12]  G. Marti,et al.  Evolution of leukemic heterogeneity of human B-CLL lymphocytes between and within patients. , 1992, Current topics in microbiology and immunology.

[13]  T. Barbui,et al.  Investigation of chronic lymphocytosis in adults. , 1988, American Journal of Clinical Pathology.

[14]  G. Marti,et al.  Anticipation in familial chronic lymphocytic leukemia. , 1999, American journal of human genetics.

[15]  G. Marti,et al.  A 20 Year Clinical and Laboratory Study of Familial B-Chronic Lymphocytic Leukemia in a Single Kindred. , 1991, Leukemia & lymphoma.

[16]  G. Marti,et al.  B‐cell monoclonal lymphocytosis and B‐cell abnormalities in the setting of familial B‐cell chronic lymphocytic leukemia , 2003, Cytometry. Part B, Clinical cytometry.

[17]  E. Kimby,et al.  Higher T-cell imbalance and growth factor receptor expression in B-cell chronic lymphocytic leukemia (B-CLL) as compared to monoclonal B-cell lymphocytosis of undetermined significance (B-MLUS). , 1989, Leukemia research.

[18]  G. Marti,et al.  Clinical Characteristics of Familial B-CLL in the National Cancer Institute Familial Registry , 2001, Leukemia & lymphoma.

[19]  M. Grever,et al.  National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. , 1996, Blood.

[20]  M. Potter,et al.  Mechanisms in B-cell neoplasia. , 1986, Immunology today.

[21]  E. Montserrat,et al.  Natural history of chronic lymphocytic leukemia: on the progression and progression and prognosis of early clinical stages. , 1988, Nouvelle revue francaise d'hematologie.

[22]  R. Braziel,et al.  Prominent clonal B-cell populations identified by flow cytometry in histologically reactive lymphoid proliferations. , 2004, American journal of clinical pathology.

[23]  R. Houlston,et al.  Familial chronic lymphocytic leukemia. , 2006, Seminars in oncology.

[24]  G. Guida,et al.  Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly. , 2004, Blood.

[25]  Natural history of stage A chronic lymphocytic leukaemia untreated patients , 1990, British journal of haematology.

[26]  P. Åman,et al.  The leukemic B-cell population of patients with monoclonal lymphocytosis of undetermined significance (MLUS) are functionally distinct from the chronic lymphocytic leukemia (CLL) derived cell population. , 1991, Leukemia research.

[27]  B. Andersson,et al.  Serum levels of helper factors (IL-1 alpha, IL-1 beta and IL-6), T-cell products (sCD4 and sCD8), sIL-2R and beta 2-microglobulin in patients with B-CLL and benign B lymphocytosis. , 1992, Leukemia research.

[28]  Kenneth C. Anderson,et al.  Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group , 2003, British journal of haematology.

[29]  B. Andersson,et al.  Serum levels of helper factors (IL-1α, IL-1β and IL-6), T-cell products (sCD4 and sCD8), sIL-2R and β2-microglobulin in patients with B-CLL and benign B lymphocytosis , 1992 .

[30]  R. Houlston,et al.  Familial chronic lymphocytic leukaemia: a survey and review of published studies , 2000, British journal of haematology.

[31]  A. Favero,et al.  Using teicoplanin for empiric therapy of febrile neutropenic patients with haematological malignancies , 1990, British journal of haematology.

[32]  W. Blattner,et al.  Familial chronic lymphocytic leukemia. Immunologic and cellular characterization. , 1976, Annals of internal medicine.

[33]  J. Fraumeni,et al.  Familial chronic lymphocytic leukemia. , 1969, Annals of internal medicine.

[34]  K. Offit,et al.  Referral for cancer genetics consultation: a review and compilation of risk assessment criteria , 2004, Journal of Medical Genetics.

[35]  Chen Wang,et al.  CD5‐negative phenotype of monoclonal B‐lymphocytosis of undetermined significance (MLUS) , 2002, American journal of hematology.

[36]  F. Mandelli,et al.  Prognosis in chronic lymphocytic leukemia: a retrospective multicentric study from the GIMEMA group. , 1987, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  Guy B. Faguet,et al.  Clone Emergence and Evolution in Chronic Lymphocytic Leukemia: Characterization of Clinical, Laboratory and Immunophenotypic Profiles of 25 Patients , 1992 .

[38]  Neil E Caporaso,et al.  CXCR4 expression is associated with survival in familial chronic lymphocytic leukemia, but CD38 expression is not. , 2002, Blood.

[39]  H. Mellstedt,et al.  Low IL-1 beta production in leukemic cells from progressive B cell chronic leukemia (B-CLL). , 1989, Leukemia research.