Monoclonal B Cell Lymphocytosis (MBL)
Written for CLLSA by Professor Chris Fegan
MB, MD, FRCP, FRCPath
Consultant Haematologist, School of Medicine,
Cardiff University January 2015
As you will have read in the Introduction CLL is a type of cancer of B lymphocytes and typically all patients are diagnosed following a blood test. Modern blood analysers can accurately measure the various types of blood cells – neutrophils, monocytes, eosinophils, basophils and lymphocytes. However, they are not able to identify B lymphocytes from the other type of lymphocyte - T lymphocytes. Indeed in a normal person ~80% of peripheral blood lymphocytes are T lymphocytes and only ~ 20% B lymphocytes. In a normal person the peripheral blood can contain up to 4,500 million lymphocytes per litre so the initial blood test would have shown a higher lymphocyte count than this but further tests would have been undertaken to show that this raised lymphocyte count was due to CLL as by definition to be called CLL one has to have 5,000 million CLL cells per litre of peripheral blood. The figure of 5,000 million per litre was simply chosen because the normal blood lymphocyte count is 4,500 million per litre as measured by routine blood analysers. Thus any patient with a blood lymphocyte count above 5,000 million per litre should be screened for CLL.
Obviously cancer has to start somewhere and we know it starts in a single rogue cell but a single cancer cell is not clinically detectable. This one cell has to develop into many thousands of millions of cells before it becomes clinically detectable – so called clonal expansion. We now have the ability to detect CLL-like cells at a very low frequency – even before the patient is ever aware - so the term MBL is used for those patients with fewer CLL cells in the blood than 5,000 million per litre and who do not have any CLL symptoms or signs of lymph node, spleen or liver enlargement.
So what happens to MBL patients with clonal CLL cells but have fewer than 5,000 million per litre of peripheral blood? Studies have shown that MBL is very common indeed with up to 3% of normal blood donors over the age of 60 having MBL and we now know up to 50% of people age >90 have MBL!!! There are some studies claiming that anyone over the age of 70 has MBL!!! In keeping with CLL, the relatives of someone with MBL have a fourfold increase themselves of having MBL.
When we became able to measure these lower levels of clonal B lymphocytes it was assumed that these smaller clones would merely grow and MBL patients would develop CLL. However we now know that in any given year only 1-2% of patients with MBL progress to CLL compared to 5-7% of patients with Rai stage 0. Thus in 10 years only 10-20% of MBL will progress to CLL. Although some studies have shown a higher risk of infection in MBL patients compared to normal people this is still significantly fewer than that seen with Rai stage 0. Furthermore those patients with MBL who do progress to CLL almost universally have lower risk CLL and a much better prognostic outlook than CLL patients presenting with Rai stage 0. Thus at present it is not recommended that widespread screening for MBL should be undertaken outside a clinical study.
Small Lymphocytic Lymphoma (SLL).
CLL is typically diagnosed following a routine blood test showing a high peripheral blood lymphocyte count. If one biopsies the lymph nodes of CLL patients who present with enlarged lymph nodes you find exactly the same CLL cells in the lymph node as the blood. The term lymphoma is used for patients who have normal lymphocyte counts but who come to medical attention either because of B symptoms or because of lymph nodes, liver or spleen enlargement. On biopsy around 10% of patients who present with suspected lymphoma have lymph nodes contain CLL cells just like a lymph node biopsy from a CLL patient. However, they can’t be called leukaemia simply because they do not have a raised blood lymphocyte count!!! So SLL patients – like MBL patients- have a normal peripheral blood lymphocyte count but unlike MBL patients have clinical symptoms and/or clinical organ involvement such as enlarged lymph nodes, spleen, liver or bone marrow infiltration. SLL is about 10% as common as CLL but should be managed in exactly the same way as they are effectively the same disease but for reasons which are not fully explained the CLL cells in the lymph nodes, liver, spleen or bone marrow of SLL patients do not circulate in the peripheral blood.
Only a handful of clinical experts have written about Monoclonal B-cell lymphocytosis (MBL) in lay language for patients understanding . One of these was Prof Terry Hamblin, who helped the first CLLSA members come together in 2005 and supported us as medical adviser. Prof Hamblin was prolific in his writing and determination during his retirement to provide patients and their families expert guidance and left us his blog Mutations of Mortality where MBL is discussed by him at length. His 2010 article What is MBL and 2011 article MBL Versus CLL atand up to the test of time and have formed much of the foundation of our understanding today.
Many of our on-line US members may be familiar with Dr Sharman. He has recently written an article and provided his expert knowledge in understandable English in his Lymphoma Blog, which is one of the most current and informative as more of the picture unfolds today.
Cheya Venkat a scientist whose husband was a CLL patient spent many years selflessly interpreting the science into language for patients and their families to understand. Cheya's website CLL Topics is no longer updated but provides us with enduring information and guidance. Much is now a little out of date but remains relevant today.
International scientific research papers
2014 Review Article BioMed Research International
2013 Pub Med
2012 Overview article PDF download