Monoclonal B-cell lymphocytosis

Monoclonal B-cell lymphocytosis (MBL) is a condition that resembles chronic lymphocytic leukemia (CLL), but does not meet the criteria for CLL, and does not require treatment. However, CLL requiring treatment develops at the rate of 1.1% per year.[1][2]

The definition of CLL includes >5,000 CLL-phenotype B-cell lymphocytes per cubic millimeter. Patients with <5,000 (but not 0) CLL-phenotype B-cell lymphocytes per mm³, and no symptoms of CLL, are diagnosed with MBL.

The term monoclonal means that all the B cells are derived from a single cell.

Causes

Little is yet known about the causes of MBL, but as it is a forme fruste of CLL the etiologies of these two conditions would be closely related. Genetic changes that can be found in CLL have also been found in MBL, and relatives of people with CLL have a much higher chance of having MBL (13% of first-degree relatives in one study).[3]

One concern about MBL is related to blood transfusions. MBL was found in 0.14% of blood donors in one study. It is unknown whether blood transfusion can transmit MBL.[4]

Laboratory diagnosis

Using flow cytometry, monoclonal cells with cell surface markers similar to those in CLL can be detected in some healthy adults, who do not meet the criteria for CLL (i.e., >5,000 CLL-type lymphocytes per mm³).[5] If the diagnosis of CLL is based on the B cell count rather than the total lymphocyte count (which includes both B and T cells), many patients formerly diagnosed with Rai Stage 0 CLL would instead be classified as having MBL.[6] Molecular techniques can detect monoclonal B cell levels as low as 3-5 B cells/microliter (comparable to the amount of stem cells in peripheral blood).[3] The term "monoclonal B-cell lymphocytosis" was proposed by a consensus committee in 2005 to indicate a monoclonal B cell population in a person with less than 5,000 B lymphocytes per milliliter (or 5.0 x 109 B lymphocytes/L), no enlarged lymph nodes or enlarged liver and/or spleen or other indications of a lymphoproliferative disorder.[7]

Epidemiology and prognosis

MBL has been found in less than 1% of asymptomatic adults under age 40, and in around 5% of adults older than 60.[7] Exact numbers depend on the population studied and the sensitivity of the diagnostic technique.[4] Like CLL, it appears to be more common in males.[4] It is also a common finding among older adults with unexplained lymphocytosis.[8]

Recent studies suggest that CLL is very often preceded by MBL,[9] and that MBL progresses to CLL requiring treatment at a rate of around 1-2% per year.[7] Advancing age and high initial B cell count predispose to progression from MBL to CLL; however, only a small fraction of people with MBL die because of CLL.[8]

Thus, MBL could be regarded as a premalignant condition from which some cases progress to CLL (much similar to the progression of some cases of monoclonal gammopathy of undetermined significance to multiple myeloma).[6]

No treatment is required, but follow-up might be able to detect new diagnoses of CLL. However, this might lead to increased costs, repeated investigations, unnecessary anxiety about cancer and health insurance concerns, while there is no means to prevent progression to CLL.[7]

Footnotes

  1. ↑ Rawstron, N Engl J Med 359:575
  2. ↑ Monoclonal B-Cell Lymphocytosis Progresses to Leukemia in Some Patients, Roxanne Nelson, Medscape Medical News, Aug. 7, 2008
  3. 1 2 Marti G, Abbasi F, Raveche E, Rawstron AC, Ghia P, Aurran T, Caporaso N, Shim YK, Vogt RF (December 2007). "Overview of monoclonal B-cell lymphocytosis". Br. J. Haematol. 139 (5): 701–8. doi:10.1111/j.1365-2141.2007.06865.x. PMID 18021084.
  4. 1 2 3 Rachel JM, Zucker ML, Fox CM, Plapp FV, Menitove JE, Abbasi F, Marti GE (December 2007). "Monoclonal B-cell lymphocytosis in blood donors". Br. J. Haematol. 139 (5): 832–6. doi:10.1111/j.1365-2141.2007.06870.x. PMID 17961190.
  5. ↑ Hallek M, Cheson BD, Catovsky D, et al. (June 2008). "Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines". Blood. 111 (12): 5446–56. doi:10.1182/blood-2007-06-093906. PMC 2972576Freely accessible. PMID 18216293.
  6. 1 2 Vogt RF, Kyle RA (February 2009). "The Secret Lives of Monoclonal B Cells". N Engl J Med. 360 (7): 722–72. doi:10.1056/NEJMe0810453. PMID 19213686.
  7. 1 2 3 4 Marti GE, Rawstron AC, Ghia P, et al. (August 2005). "Diagnostic criteria for monoclonal B-cell lymphocytosis". Br. J. Haematol. 130 (3): 325–32. doi:10.1111/j.1365-2141.2005.05550.x. PMID 16042682.
  8. 1 2 Rawstron AC, Bennett FL, O'Connor SJ, Kwok M, Fenton JA, Plummer M, de Tute R, Owen RG, Richards SJ, Jack AS, Hillmen P (August 2008). "Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia". N. Engl. J. Med. 359 (6): 575–83. doi:10.1056/NEJMoa075290. PMID 18687638.
  9. ↑ Landgren O, Albitar M, Ma W, et al. (February 2009). "B-Cell Clones as Early Markers for Chronic Lymphocytic Leukemia". N Engl J Med. 360 (7): 659–667. doi:10.1056/NEJMoa0806122. PMID 19213679.
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