Is MBL the same as CLL stage 0?

[Jazzandblues]

hi. I recently got diagnosed with MBL and I’m reading a lot about CLL stage zero on this board. I’m a little confused with the terminology. I’m trying to understand if it is the same thing or not can anyone help?

[Newdawn Administrator]

Much depends on whether it’s high count or low count MBL. Whereas low-count MBL rarely progresses to CLL, high-count MBL progresses to CLL requiring therapy at a rate of 1% to 2% per year. High-count MBL is distinguished from Rai 0 CLL based on whether the B-cell count is above or below 5 × 109/L.

In 1–2% of cases, high-count MBL progresses to CLL requiring treatment. It’s sometimes referred to as a precursor to CLL but there’s no certainty that it will progress.

MBL is therefore not classed as a cancer and may never develop beyond mild lymphocytosis. A flow cytometry test is required to distinguish the distinctive cell patterns which confirm CLL.

‘MBL is defined as a clonal B-cell count less than 5.0 × 109/L in the peripheral blood without evidence of lymphadenopathy, organomegaly, or extramedullary involvement.’

ncbi.nlm.nih.gov/pmc/articl....

Hope this helps.

Newdawn

[SeymourB in reply to Newdawn]

Newdawn -

Can MBL also progress to SLL, where the white count remains below 5 × 109/L, but lymph nodes and spleen swell?

=seymour=

[Newdawn Administrator in reply to SeymourB]

That’s where it starts to become quite complex Seymour and although a now very dated article (‘blog’), I can’t answer this remotely as well as the late, great Terry Hamblin. The follow up questions reflect the complexity of the subject though I appreciate there have been many scientific and treatment developments since this time. The principles remain the same and it’s always good to read back on his thoughts.

mutated-unmuated.blogspot.c...

The difference of course is a need to test differently using the nodes as opposed to the peripheral blood. As a SLL’er, Neil will no doubt have greater personal experience of this but I don’t ever recall him mentioning the possibility of him having MBL.

If as you say there’s evidence of swollen lymph nodes and spleen, the final line of my last post would seem to apply. It’s highly likely that SLL is more likely than MBL where there’s evidence of ‘lymphadenopathy, organomegaly, or extramedullary involvement’ even the absence of lymphocytosis.

Newdawn

[AussieNeil Partner Administrator in reply to Newdawn]

SeymourB and Jazzandblues, as Newdawn notes, what differentiates MBL from SLL is whether there is any involvement other than the blood; "It’s highly likely that SLL is more likely than MBL where there’s evidence of ‘lymphadenopathy, organomegaly, or extramedullary involvement’ even the absence of lymphocytosis."

"Extramedullary involvement (EMI) refers to leukemic cells found in organs or tissue outside the blood or bone marrow. The most common sites of extramedullary disease are skin, bone, and lymph nodes."

I was diagnosed at stage 1V CLL/SLL because of "lymphadenopathy, organomegaly" specifically an enlarged spleen protruding below my rib cage, and a scattering of enlarged nodes, cytopenias (low neutrophil and platelet counts due to bone marrow involvement). My specialist specifically gave me a diagnosis of CLL/SLL, though I met the 'SLL' criteria. I would have been bordering on having a diagnosis of high count MBL if it hadn't been for the other than blood involvement. There were enough monoclonal CLL phenotype B lymphocytes in my blood for flow cytometry identification. ('SLL' is commonly diagnosed from a node or bone marrow biopsy.) About 2 years after my diagnosis, my lymphocyte count moved into 'CLL' territory.

Jazzandblues, even if you have high count MBL and it develops into CLL/SLL, you may never need treatment. What's important is that you appreciate that by definition, you are now (slightly) immune compromised. Given that your immune system function is unlikely to improve with time, now is the time to get up to date with all your non-live vaccinations. Keeping them up to date healthunlocked.com/cllsuppo... is the best way to reduce your now higher risk of death from infection.

Neil

[Jazzandblues in reply to Newdawn]

thanks so much for this. So It’s not the same as CLL stage O.

[Newdawn Administrator in reply to Jazzandblues]

My understanding is that it is not the same as CLL stage 0 but some doctors do use the expression and it confuses patients.

I suspect they may use it more with high count MBL where they’re monitoring counts with more expectation of a development to CLL. MBL is not classed as a cancer however.

Newdawn

[SeymourB in reply to Newdawn]

Newdawn -

I think that doctors mentally file their MBL patients along with CLL stage 0 - i.e. just watch, no enlarged nodes. 6-12 month test interval is likely.

I think doctors are also often clueless about immune dysfunction in both groups. You should certainly get vaccines, but it might be good to get vaccine titer tests before and after vaccination, or a COVID spike IgG test 6 to 8 weeks after a COVID vaccine as a rough gauge of antibody response. Bear in mind that antibodies are only part of our immune system, but be more cautious in crowds and wash hands more frequently during cold, flu, COVID, and RSV season if antibody responses are low.

=seymour=

[Newdawn Administrator in reply to SeymourB]

I’ve no doubt that they do Seymour especially GP’s and primary physicians who may not have the same level of understanding. I clearly had MBL and my GP and a local haematologist had discussions about my situation (I wasn’t aware). The haematologist told him he wasn’t interested in taking on cases of lymphocytosis and my ALC was about 12 before he tested me. Only after the flow did I receive a definitive CLL dx. He told me he knew I’d ‘suss him out’ when I insisted on pursuing testing. Thankfully we had a good relationship.

Even then my GP said he preferred to think of it as lymphocytosis rather than a cancer and I replied that he could refer to it as a verruca if he preferred but I knew it had the potential to kill me! 😉

Newdawn

[lankisterguy Volunteer]

Hi Jazzandblues, &    SeymourB ,

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The only absolute about CLL is that it does not follow absolute rules (also called "heterogeneity") , and neither do our doctors & medical associations. Groups like the iWCLL20018, NCCN and NHS attempt to provide guidelines or suggested terminology, and these keep evolving as more data becomes well known.

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A narrower definition of CLL only became suggested by the USA NCI in 1988 and refined in 1996. About the same time frame the formerly separate diagnosis of SLL was recognized as being the same disease as CLL. And as the immunophenotype testing improved and became more cost effective, the experts discovered that many people had lymphocytes with the characteristics of CLL but did not ever develop a increasing number of those cells. So the category of MBL was defined, and then revised a few times.

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So I would submit that the definitions are fluid and evolving, and the understanding and use of those terms by our medical professionals is also fluid and evolving.

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ncbi.nlm.nih.gov/pmc/articl...

SNIP: Chronic lymphocytic leukemia (CLL) is one of the most common lymphoid malignancies in the Western World. Criteria to formalize the diagnosis of CLL were developed by the National Cancer Institute (NCI) in 1988 and underwent revision in 1996

According to these criteria, individuals with a lymphocyte population that expresses B-cell markers (CD19, CD20, and CD23), the CD5 antigen, and dim surface immunoglobulin along with a peripheral blood absolute lymphocyte count (ALC) ≥5.0 × 109/L are classified as having CLL

1. More recently, the advent of highly sensitive, multicolor flow cytometry techniques has revealed that approximately 3% of the population over the age of 40 has a circulating population of clonal lymphocytes with a CLL phenotype in the absence of lymphocytosis

2. The frequency of this finding is even higher among first-degree relatives of patients with CLL

3. Individuals with this combination of peripheral blood findings have been classified as having monoclonal B-cell lymphocytosis (MBL).

While the natural history of MBL continues to be defined, it is clear from data on the incidence of CLL that the majority of individuals with MBL will not develop CLL. To ensure uniformity of diagnosis and thereby facilitate studies of the biology and natural history of MBL, the International Familial CLL Consortium recently published formal diagnostic criteria for MBL

4. These criteria classify individuals with a monoclonal B-cell population in the peripheral blood, a B lymphocyte count 5.0 × 109/L rather than an ALC ≥5.0 × 109/L to establish the diagnosis of CLL5.

While this modification is intended to improve diagnostic precision, it was not based on objective evidence and involves re-classifying the diagnosis of patients from a leukemia diagnosis (CLL) to what is thought to be a pre-malignant condition (MBL) if their B lymphocyte count is <5.0 × 109/L. Ideally, such revisions to diagnostic criteria should be based on objective determination of the elements that best characterizes patient’s clinical outcome.

If you want to read the history in depth here are some articles ( most written in MedSpeak):

onlinelibrary.wiley.com/doi...

ncbi.nlm.nih.gov/pmc/articl....

pubmed.ncbi.nlm.nih.gov/235...

-

Len

[SeymourB in reply to lankisterguy]

lankisterguy -

I found an additional article that sheds light on some possibly useful testing that might distinguish LC-MBL (Low Count MBL) from HC-MBL, and progression to CLL:

ncbi.nlm.nih.gov/pmc/articl...

Understanding Monoclonal B Cell Lymphocytosis: An Interplay of Genetic and Microenvironmental Factors

Front Oncol. 2021; 11: 769612.

So the question becomes, should we bother to do additional tests to detect MBL cases that will probably progress to CLL. The same issue exists in CLL - how much testing how early?

After 12 years of Watch and Wait, and now in treatment, I think less early testing can equal less anxiety for many people. A few want to know as much as possible (me). But it's by no means a guarantee. Psychological counseling is needed for anything that feels like doom.

=seymour=

[Newdawn Administrator]

I’m not sure where you’re from Jazzandblues so don’t know which staging system your doctor will use. It’s usually the Rai staging in the USA and Binet in the U.K. This may help you to understand the staging because it’s not difficult to see why this is so confusing;

cancerresearchuk.org/about-...

In that Stage 0 on Rai says;

stage 0 - you have a high number of lymphocytes

it must be puzzling when MBL also has that sole characteristic. However, a definitive CLL diagnosis requires more and certain characteristics are required on the flow cytometry test.

‘The diagnosis of CLL is often made incidentally on a routine full blood count, showing lymphocytosis (total lymphocyte count >5.0 x 109). The immunophenotype displayed on flow cytometry shows a monoclonal population of mature B lymphocytes expressing a unique phenotype of CD19+, CD20+,CD5+ and CD23+.

When this cell pattern is seen exclusively on lymph node biopsy with peripheral blood component <5 x 109, the diagnosis is small lymphocytic lymphoma (SLL). The World Health Organization (WHO) considers SLL and CLL to be biologically the same disease’.

Hope your situation remains in the MBL camp. Remember, a very high percentage does and is more common than people imagine.

Regards,

Newdawn

[Jazzandblues]

thank you so much. I’m actually in the UK

[Pacificview]

Hello and a very warm welcome to our community here.

After reading your post. I am thinking we have very little info on you. We do not know whether you are low count MBL or High Count MBL. It makes a big difference! Because most people with low count MBL never progress to full blown CLL/SLL. So a very important question I would ask my Doc is, am I high count or low count? If your low count its a thank you Jesus moment for you.

If you are high count, then you will want to know what your markers are. As they usually will give a good idea of the disease course

Your Docs should already know whether your high count or low. Since they gave you the MBL diagnosis.

So find that out and let us know? I will be praying that it is low count...

John

[Jazzandblues]

Lymphocytes, 5.9 of which 53% mono B cells. My understanding is that is HC. Lymphocyte numbers rose out of normal in May 2020 which makes me wonder if it was Covid (March 2020 pre vaccination) waiting to hear if it is genetic. I had cellulitis in my arm May 2023 and a dull ache behind my left rib so decided to get a scan. They saw a slightly enlarged spleen which led to a haematologist visit and a diagnosis of MBL. I’m female 54 from the UK.

[Jazzandblues]

The slightly raised lymphocytes in May 2020 were not picked up. The presumption must’ve been that it was just a post Covid number. It’s only looking back at my bloods that I saw things had started to rise then.

[blueloon]

Hi there, this is my first reply on this forum -I’m 57, from Canada and I also have MBL. I was diagnosed 2 years ago with high count MBL after a flow cytometry was completed. I also had an ultrasound done for my spleen which was fine. I had no other symptoms other than an elevated lymphocyte count @6.

I saw two hemotologists for their opinions and both stated that MBL is benign. MBL can possibly progress (as some of the previous responses have outlined). MBL can also revert back, undetectable. They said to carry on with normal life and keep stress to a 0. After climbing down from my mountain of worry, I put this diagnosis on my back burner and moved forward.

Fast forward to today - I just had my annual followup with my hemotologist and I remain MBL. They look at my bloodwork, check my lymph nodes, ask questions, and always go through a checklist for symptoms. My lymphocyte count was normal however increases to the high range (5-12) sometimes. I also have an autoimmune condition which requires monthly IVIG and daily low dose prednisone - both of these play with one’s bloodwork count. Infections will also change your CBC.

If my lymphocyte count doubles or the pattern is continuous elevation then at that point the hematologist will request another flow cytometry test to decipher the possibility of progression to CLL.

I hope you stay positive and ask as many questions as you can when seeing your hematologist. It’s so important for peace of mind and keeping stress to a minimum. My hematologist is a phone call away so if I see anything suspicious or head scratching on my bloodwork I call.

I also recommend starting a “medical binder” for yourself. Keep all records/results/notes/doctor’s notes/checklists etc in one place. This is also a great way to track/compare results. I never thought I’d have one of these but I love having it. It keeps me organized and is handy to have in doctor appointments.

Keep well and stay positive. Stay informed and never hesitate to ask questions. You are your own best advocate.

[Jazzandblues in reply to blueloon]

Thank you so much. Wishing you well.

[DanBro1]

I am unaware that CLL has "stages"........

[AussieNeil Partner Administrator in reply to DanBro1]

As Newdawn noted there are two staging systems used for CLL, RAI and Binet healthunlocked.com/cllsuppo... SLL being a lymphoma can also be staged with Ann Arbor. Unlike most other cancers, CLL/SLL staging is more about assessing the degree of bodily impact of the disease than determining when treatment is required.

Neil

[Odinn]

MBL is not CLL, it can turn into CLL but the percentage that progress is low. Repeating tests and when it is done depends on what your blood count was. Mine was 4100 so I was told it was High Count MBL. At this point they will monitor for symptoms and do blood counts again in a year. Per my doctor most people with MBL live a normal life span. You do have to watch for infections and keep up on your vaccinations. I was told that having High count MBL that I was considered immunosuppressed and should be aware. Just follow up with your doctor.

[Pacificview]

Jazz,

I was origonally diagnosed with CLL/SLL after flesh from a prostate procedure was sent routinely to patholgy for exam.

Results came back, and in those results it was discovered that my prostate was infiltrated with CLL/SLL.

So my Urologist sent me off to a oncologist. I had no symptoms of CLL/SLL at the time except for a swollen prostate with associated symptoms.

So the Oncologist sent me off for all the standard tests and then some. One of those tests tells you how large your Monoclonal B cell population is.

Mine came back with a monoclonal B-Cell population that was just high enouh to place me as High Count MBL according to the lab.

So I was High Count MBL. So next I wanted to know what converts my MBL into CLL?

On my Charts it already said I had a non hodgkins lymphoma/ CLL/ SLL diagnosis.

So I was thinking, hey not so fast. I am MBL which is not cancer right? So I can't have the non hodgkins lymphoma/ CLL/SLL diagnosis or can I?

So I went on a research hunt. Why does my chart say that I have cancer? Tecnically I am HCMBL, why does everything with my name on it say Non hodgkins lymphoma CLL/SLL?

Well, because they found a monoclonal B Cell population that has CLL/SLL markers on the fish test. Yes, but I have HC MBL which only has a 1 to 2% chance per year of turning into CLL/SLL!

So I took this question to my New CLL/SLL team a Duke University. Dr. Brander.

I asked to clarify what is the difference between HCMBL and CLL/ SLL. Because I am thinking maybe I will never morph into this cancer called CLL/SLL. How do I morph from a worm to a butterfly anyway? Mbl to CLL, how does that happen?

She told me it was the size of the monoclonal b cell population. If the monoclonal b cell population grows enough to move past LC MBL. You are then classified as technically HC MBL. If that monoclonal b cell population grows more. You move out of the MBLs and into CLL/SLL. THE ONLY REAL DIFFERENCE IS THE SIZE OF THE MONOCLONAL B CELL POPULATION. To move you from one classification or the next. Now, this is true if your fish test comes back as positive for a CLL/SLL monoclonal b cell population! You have to test positive for that CLL/ SLL markers. Because those markers identify your monoclonal B cell population as CLL/SLL.

But if you have the markers and you are still low count MBL. The odds of that population growing to high count MBL and then growing to CLL/SLL are slim.

So this is why the answer to the question is important. Are you high Count MBL or low Count? Then do you have CLL/ SLL markers or some other Non hodgkin Lymphoma markers?

If you have a growing mono b cell population but do not have markers for CLL/SLL or some other form of non hodgkins lymphoma. Then you have lymphocytosis. As you have a growing population of lymphocytes.

Then the Docs will look for some other reason causing the lymphocytosis.

[Azzurrina in reply to Pacificview]

You have been diagnosed with the cd5 cd19 cd23? Are those the markers to classify it as CLL? I was POSITIVE for cd5 cd23 cd38(12%) and fcmd, but not the cd19.

[Pacificview in reply to Azzurrina]

First flow cytometry after diagnosis after CLL found in biopsy.Hope this helps...

Black and white

[Jazzandblues]

thanks. That’s what I’ve also discovered. I have HC MBL and do have the markers. Watch and wait. 6 month bloods. Get hot at night which disrupts sleep on many occasions. Doing my best to stay positive. Not easy on the nights you don’t sleep well. Any advice on the disrupted sleep?

[Pacificview in reply to Jazzandblues]

Try taking some diaphenhydromine...(benedryl)Works pretty good for sleepyness.