Had my initial appointment with a Haematologist today who said I have Clonal Lymphocytosis. Can I ask how many of you started with Clonal Lymphocytosis and it develop into CLL?I am 47 and have had rising lymphocytes for the past 5 years.
Clonal Lymphocytosis : Had my initial... - CLL Support
Clonal Lymphocytosis
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Ambrose04
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I don't feel confident enough to hazard a guess, the articles I found that is current is deep and I'd need to do some close reading. It could send you down the wrong path. Someone more experienced than myself will take a crack at it sooner than me. I won't be able to reply until I understand it enough. A little knowledge is a dangerous thing.
But don't feel down, I just don't want you to feel ignored. I will post the links after I verify they are of any use.
🙂
AussieNeilPartnerAdministrator
Could you please list your last few lymphocyte counts - the absolute values, not the percentages.
The precursor to CLL is Monoclonal B Cell Lymphocytosis, MBL, the incidence of which becomes increasingly common in the general population with age. MBL can be either low or high count. Low count MBL is unlikely to progress to CLL, while there's a risk of progression of 1 to 2% per year for high count MBL.
Flow cytometry is the test used to identify what specific blood cancer comprises the clone. While MBL/CLL is the most common adult leukemia/lymphoma, others, such as Follicular Lymphoma and Mantle Cell Lymphoma and even rarer blood cancers are possible.
Neil
Thanks for your reply. I'm not sure I know my absolute count, all I know is my last fbc came back as lymphocytes 18.3.The haematologist I saw today said he would be able to tell me more when he gets today's blood results back some of which are genetic testing so he said could be 5-6 weeks.
Sorry to be so fague with my information.
If you have had rising lymphocyte counts for the past 5 years, the good news is that you have a slowly growing, that is chronic, cause for your lymphocytosis, so it's probably chronic B cell lymphocytosis, most likely CLL. There has been a revolution in the treatment of CLL and its close cousins in the past decade, with new and improved drugs regularly becoming available.
On your FBC, there's a section called the differential. Brief versions show the total WBC and percentages of different white blood cell types. Usually, a more extended presentation of the differential is provided, where both the percentage and absolute counts of the different white blood cells are given. If your absolute lymphocyte count is 18.3 and you have B cell lymphocytosis with the characteristics of MBL/CLL, you are definitely into CLL territory. What stage you are is determined by where else in your body the clonal B cells are accumulating.
Neil
Yes its definitely a slow progresser so far which is good. I'm having a scan on my spleen and liver as I'm getting alot of discomfort on side.
This first article is only hinting at a perhaps more accurate way of prediction as the older methods are relating less to actual outcomes. The most important take away in prognosis is really in informing your doctors if treatment approaches what may be the best course to take. That I add this article is only informational to show us not to be frustrated with the older less reliable information floating around the internet. We're improving but not there yet.
"In summary, the authors have identified a new signature to identify individuals with HC-MBL with a particularly high risk of progression to CLL, who also appear to have a shorter OS. Although this new prognostic signature is promising, further validation in independent data sets is crucial,... Moreover, given the diverse treatment regimens received by patients in the collected cohorts over the long time span of the study, the OS data may not be reflective of current treatment practice and might therefore be a less definite finding.
Therefore, assessing the impact of the ELCLV3-21 signature in more homogeneously treated cohorts, in particular in relation to targeted therapies such as Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors, is essential".
(added emphasis my own)
[ashpublications.org/blood/a...]
In short, this second article states, "MBL detection is based on the identification of B cell expansions in the blood circulation with the characteristic “CLL-specific” phenotype, yet of a smaller size than the one required for CLL diagnosis. This criterion, based solely on a mathematical cutoff is devoid of any biological context, perhaps hampering our understanding of the mechanisms driving disease onset. Thus, the in-depth characterization of MBL holds great potential for understanding the mechanisms that represent major drivers in the process of its transformation to CLL. (again with my added emphasis) [frontiersin.org/journals/on...]
My crude explanation is that this shows the promising potential of understanding the interplay of MBL with CLL further study may very well be fruitful.
Personally, AussieNeil's direct informational gathering is going to be of far more practical use to you. As you get your bearings this may be of interest later on. It really is more of a demonstration of the complexity of the disease, the varied sometimes baffling differences of CLL, and the wonder of the complexity of our natural immunological system.
Oh, Welcome! 🙂
Thank you for all the info will definitely have a good read up, and thanks for the welcome. It certainly is a very complex condition to get your head around.
Like you I was initially diagnosed with MBL due to rising lymphocytes over the past 12 months but that diagnosis has recently been changed to CLL following genetic testing.
Still trying to get my head round it but it seems I have a slow developing type of CLL, with the IGHV mutation and not TP53. Hopefully no need for treatment for some time yet - my lymphocytes were 21 at last test and I’ve been told treatment is unlikely until I develop any symptoms or my count goes over 100.
After 21 years of living with another indolent type of blood cancer (ET), which I still have, I’m familiar with the various tests, acronyms etc for that but now having to learn a whole new set of them for CLL..!
Thanks for your reply. He's done some blood tests for genetic testing along with others and said he would have a better idea of what's going on once these come back. I am terrible at waiting and unfortunately the genetic ones can take 5-6 weeks to ome back.If my spleen or liver is enlarged does that change it from MBL to CLL or is it blood counts alone that?
Spleen enlargement can be a symptom of CLL as the malformed CLL cells build up in your blood and get filtered out by the spleen. Typically this presents as pain below the lower left rib cage and/or a feeling of fullness and loss of appetite. This usually wouldn't happen until higher ALC counts though.
I don't believe liver is generally impacted by CLL but it definitely can be during treatment.
If your doctors have identified such swelling, there might be other issues.
For those starting out on the CLL journey, cllsociety.org is a good resource to get the lay of the land. Look under Info & Mgmt for the Newly Diagnosed tab.
In general, CLL is a slowly-progressing disease and, unlike most cancers, there's good statistical evidence that the best course of action is to "watch and wait" until more significant health impacts emerge. And there are good treatment options. So even if you are diagnosed with CLL, many patients have a close-to-normal life.
The genetic tests are more to map out a treatment plan... CLL treatments and progression vary quite widely and the genetics will help make informed choices about frequency of checks during watch-and-wait and treatment options down the line.
Try not to stress. Read up a bit. If you do have CLL (sounds to me like you might based on your numbers), you have plenty of time to figure it out.
Down the line you will want to look into having a CLL specialist as part of your care team. They can supplement your hematologist. cllsociety.org will walk you through that.
Not sure of the significance of spleen and liver in CLL. Mine are normal and monitored as part of my other condition.
It seems like genetic testing is the gold standard for CLL diagnosis but blood counts and B symptoms (fever, unexplained weight loss and night sweats) are significant too - I don’t have any of those symptoms.
I’m not good at waiting either! I know so much about my other condition that it’s frustrating me to start all over again with CLL. I have a lot of faith in my haematology team but like to know the details not just top line!
Spleen my.clevelandclinic.org/heal... The spleen is the major lymphatic organ. As CLL is a cancer of the immune system the spleen swell not more football games, seat belt low over hips, and yes a large spleen can be removed but it is not usually because even if it isn't healthy it serves a purpose better than being without one.
Thanks - that’s interesting to know. Splenomegaly can also be a symptom of MPNs, the myeloid conditions that my ET belongs to, as it takes over blood cell production when the bone marrow starts to fail.
Spleen removal used to be more common in those conditions too but is largely avoided now by the use of targeted therapies that bring its size down as well as addressing other problems.
Most of us would have been diagnosed either having developed CLL/SLL symptoms, or on the basis of a high ALC following a routine blood test. Most of us would be unaware of any prior lymphocytosis.
As Neil has said, low count MBL is fairly common in the population, more so with age, yet only a small minority of those cases progress to high count MBL and CLL. CLL being a rare disease, it's a valid question to ask: if you have CLL, does that mean you necessarily had low count MBL in the past? The answer, from large studies, is yes. nejm.org/doi/full/10.1056/N...
I have seen smaller studies that recorded low count MBL in patient cohorts up to 16 years prior to CLL diagnosis sciencedirect.com/science/a...
As 5-10 % of CLL is hereditary, it could be that low count MBL in those cases and some others, is established very early in life, coming to light as CLL several decades later.
I assume that a 100%. All CLL starts with clonal lymphocytosis. But not all clonal lymphocytosis develops into CLL.
Yes thats my understanding of it too. I also think that high count MLB is likely to develop than low count.
LCMBL much more prevalent than HCMBL.
All hounds are dogs not all dogs are hounds.😀
Some greyhounds are buses.
😆Sandra
CLL is assumed to proceed from a single B lymphocyte with one or more mutations key to its survival, hence clonal lymphocytosis.
This is still an assumption, because that early a stage in the history of the disease has never, to my knowledge, been observed. The origin of CLL is, like the Big Bang, a theory.
The origin is one thing. From LCMBL through HCMBL to CLL is the progression.
SLL origininates in a lymph node. The NCCN guidelines recognise this, noting SLL can potentially be cured by radiotherapy if caught when restricted to a node or a few, localised nodes. Unfortunately, SLL generally goes undetected until it is too well established, unless the originating node is in an obvious location. We have had a few members join with localised, potentially curable SLL.
CLL, on the other hand, originates in the bone marrow.
Neil
Thanks for the ref. I can only open the version for patients, so my question is: how do we know? I thought that all B cells are made in the marrow and mature in the nodes, and in SLL they stay there.
Annoyingly the NCCN guidelines prohibit quoting. 
Both CLL and SLL cells most certainly accumulate in the bone marrow, which is why other blood counts fall. It was the development of cytopenias that led to my diagnosis while my lymphocyte count was on the normal range.
About 10 years ago, one theory for the development of CLL, for which its incurable nature was one argument, was that it arose in a lymphoid stem cell which wasn't touched by chemo and from what it could rebuild. That hypothesis seems to have gone out of fashion.
Neil
You just have to register an account on NCCN, easy as 1,2,3,4! Then click the link in verification e-mail. I'm a "Patient or cancer survivor".
iSRT - involved-site radiation therapy
nccn.org/professionals/phys...
Yes thanks guys. I did register but it might as well be NIH guidelines (Needle In Haystack). Do they really have anything to say on the origins of CLL and SLL?
While the NCCN guidelines don't say anything about the origins of CLL and SLL, targeted radiotherapy wouldn't be effective if the CLL/SLL wasn't restricted to localised nodes.
Thanks. Re CLL and SLL it seems our respective concepts of 'origin' differ.
It would be interesting to know why some folk develop one, some the other. I guess there's a spectrum, with 5 ALC in peripheral blood the dividing line for definition purposes. I read in an old paper that 15 % of SLL cases (in the study) were preceded by MBL.
Neil, So if SLL originates in the nodes and the blood work is normal is the bone marrow impacted yet? I haven't had a BM biopsy and have always been curious if I have infiltration. From your comment I'm thinking significant BM impact is low.
Bigfoot
I know you didn’t ask me but in the meantime….
If you have SLL your bloodwork can look rather normal. I finished treatment with a partial response and my lymphocytes in the blood are 0.5. But, BMB says close to 15% of all cells in the sample are CLL/SLL cells. MRD last week in blood is 0.31. I think the Z+V trial got all the easy cells and the belligerent CLL cells are still in the nodes and marrow. My uninformed interpretation.
I also recall someone on healthunlocked did a degrader clinical trial at U Penn. Their peripheral blood was clear but the bone marrow was completely packed.
So my interpretation is: Yes, sometimes for some people the bone marrow can be impacted while the bloodwork is normal. I can’t state any statistics for the average CLLer.
Somewhere I read that at the time of diagnosis with CLL, the bone marrow is typically around 20% infiltrated. At the time of starting treatment, I've seen cases where members who've have a bone marrow biopsy prior to starting treatment report over 90% infiltration. CLL/SLL is a highly heterogeneous illness and that's also the case with the degree to which CLL/SLL infiltrates the bone marrow and which blood counts are impacted. For some, red blood cell production and hence haemoglobin takes the initial hit, for others, it's platelets and for others it's neutrophils (which makes sense when you appreciate that neutrophils comprise about two thirds of a healthy white blood cell count and neutrophils only last a matter of a week or less).
What's important to realise as you get closer to needing treatment, is how much bone marrow production capacity you have left and the impact of further bone marrow infiltration or suppression. If your bone marrow is 50% infiltrated, a further 5% infiltration still leaves you with 45% infiltration or 90% of your previous blood cell production capacity. The same 5% increase in infiltration when you are at 90% infiltration, leaves you with just 50% of your previous blood cell production capacity. So when you get to around 90% bone marrow infiltration, you are likely to soon drop out of the optimal treatment window, particularly if other indications of tumour growth are showing fast progression.
With an SLL presentation, you miss out on the ALC growth indicator, so you are more reliant on tracking changes in spleen and node sizes and downward trends in haemoglobin/red blood cell counts, platelet and neutrophil counts to assess your progression.
Neil
Thanks Neil. Great explanation.
Thank you. I appreciate the response. That was my assumption, but where and when the nasty CLL cells camp out is always a bit of a mystery.
I seem to have created quite a discussion. Thank you so much for all the information.
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