ESH CLL 2022 | MBL: low vs. high count and CLL progression
Alberto Orfao, MD, PhD, University of Salamanca, Salamanca, Spain, shares some insights into monoclonal B-cell lymphocytosis (MBL) in chronic lymphocytic leukemia (CLL), highlighting some important points to consider when investigating low-count and high-count MBL. First, Dr Orfao explains the importance of identifying low-count MBL patients with a high-risk of progression and the role that age plays in disease. Following this, Dr Orfao discusses the need to better understand why these clones appear in patients, and the potential role of the B-cell receptor in the development of MBL. To conclude, Dr Orfao explains the need to further investigate the consequences of having small clones of B-cells and the mechanisms involved in disease progression to CLL. This interview took place during the 2nd ESH Translational Research Conference on Chronic Lymphocytic Leukemia (ESH CLL), 2022.
Transcript (edited for clarity)
I think that there are probably three major points. The first point is how can we identify, and if possible at the earliest stages as possible, those cases that have MBL, even MBL low, but they have a high risk of progression. At present, this is becoming easier and easier in MBL high count, but still at the moment, we don’t have variables that would help predicting progression in MBL low to MBL high in CLL...
I think that there are probably three major points. The first point is how can we identify, and if possible at the earliest stages as possible, those cases that have MBL, even MBL low, but they have a high risk of progression. At present, this is becoming easier and easier in MBL high count, but still at the moment, we don’t have variables that would help predicting progression in MBL low to MBL high in CLL. For sure, age plays a role in terms that if you detect an MBL, particularly an MBL low count at a very advanced stage, the time it will most probably take to develop CLL is longer than the life expectancy of that particular individual, but it might get a high relevance in younger adults with even very small CLL clones or CLL-like MBL clones. That’s the first point.
The second point is why do we get these clones appearing so frequently? So, what is the reason to develop, in parallel with aging, these MBL clones now at the stage of low count MBL? Even if there is the general belief that B-cell receptor stimulation is probably the origin, there is no solid data really placing or identifying the list of causes and co-factors for developing MBL in adults.
The third relevant part is what is the consequences of having for decades in your life, small clones of B-cells in the normal residual B-cells, and more generally in your immune system, and how this affects the known risk increased for infection and even severe infections? There, there is some preliminary data indicating that particularly the B-cell responses and structure are affected, but understanding why they are affected and what are the mechanisms involved remains a challenge.
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