Why, with Chronic Lymphocytic Leukaemia, CLL, White Cell percentages can be dangerously misleading. You may not be neutropenic!

[AussieNeil]

Frightened by falling neutrophils? Worried about being at a greater risk of infection? This is a common and often totally unnecessary fear, simply because standard blood count reports give more emphasis to presenting the percentages* of the different white blood cell types than the absolute counts. They may not even provide absolute count figures. If so, this is the ONLY time you need to look at percentages† , so that you can calculate your absolute counts.

The accompanying image includes two plots from typical results for a CLL patient with a lymphocyte doubling time of about 8 months. The top plot shows neutrophils dropping - or does it? This plot just shows the percentage of neutrophils dropping. If you look at the absolute count plot in the lower plot and in the included table, you'll see that the neutrophil counts are excellent and actually improving! (Purple solid line). That's because with CLL, your lymphocyte count typically rises (dotted blue line) and the total percentages of all the white cell types must add up to 100%. So when your lymphocyte count increases, the percentage of lymphocytes also increases, provided other white cell absolute counts have not changed much. You can't exceed 100% in your total percentage of white cell types, so the other percentages must fall. Neutrophil counts may even increase slightly while their percentage falls, as in this example, where the absolute neutrophil count has risen 28% over the year.

Commonly in blood test reports, the white cell count types are reported in what's termed a blood differential test. This measures the amount of each type of white blood cell (WBC) that you have in your blood sample. There are typically white cell five types listed, here provided in decreasing count order:

- Neutrophils or Segs (normally about 65% of the total) Reference range ~2 to 8

- Lymphocytes (which include CLL cells plus healthy B and T cells and normally about 30% of the total. This is why it is important to monitor your lymphocyte count, not your WBC with CLL: healthunlocked.com/cllsuppo...

- Monocytes

- Eosinophils

- Basophils

(I've lumped these last three types into 'Rest' in the plots above)

I seem to be spending more time lately, reassuring members that they probably do not have a problem with falling neutrophil counts (i.e. at risk of developing neutropenia). Hence this post. It's extremely important to be aware of your neutrophil count, because our neutrophils are so important in keeping us free from dangerous bacterial and fungal infections. During watch and wait, they can fall as our bone marrow becomes more infiltrated with CLL and all CLL treatment drugs carry with them the risk of neutropenia.

Neutrophils quickly respond to infections. They cause a wound to become red and swollen as the neutrophils move out of the blood into the tissue around the wound, where they engulf bacteria and fungi along with dying body cells. When they have done all they can to protect you from infection, they die, forming pus. This post covers neutropenia precautions: healthunlocked.com/cllsuppo...

This video by Dr. Erel Joffee, lymphoma specialist with Memorial Sloan Kettering Cancer Center, recorded for the USA's Leukemia and Lymphoma Society, covers both neutropenic fevers and how to interpret blood counts. Note his words from the 6:38 mark, especially from the 6:50 mark, "You should only look on the absolute numbers. You should look if the absolute numbers are within the reference, not the total number and definitely should not look at the percentages... The percentage of the neutrophils, lymphocytes, monocytes and so forth are completely irrelevant and please do not look at them."

youtu.be/ScXCNf_WUZM(Not working as expected?)

Also note his remark at the 9:21 mark, with respect to absolute lymphocyte counts. "If the patient is asymptomatic, absolute number, we don't care."

A useful analogy for why absolute counts, not percentages are so important is to think of two belligerent countries. If we consider neutrophils as aircraft (air supremacy being so important in warfare), the country with a greater percentage of aircraft in its defence forces would not go to war against its foe if that foe had absolute supremacy in aircraft numbers.

* White cell differential percentages are great for your GP/PCP for 99.99% of their patients. CLL is a rare cancer, so most doctors would only see a few cases in their entire career. The percentage differential provides a quick, at a glance indication of any imbalance in white cells, typically indicating an infection or allergy. However, when you have CLL, percentages do far more to confuse than to help. Ignore percentages and concentrate on absolutes. Please!

† If absolute counts are not provided on your blood test report, you can easily work them out by multiplying the WBC count by the percentage of the white cell you want to know. For example, in the image above, the total WBC in January is 33.4. The percentage of neutrophils in January is 8.7% (rounded to 9% in the table). 33.4 x 8.7% = 2.9, which is the absolute neutrophil count for January.

Blood count tracking spreadsheet templates are available per this post: healthunlocked.com/cllsuppo...

Neil

This post is unlocked/open for discovery on the Internet, it's so important.

healthunlocked.com/cllsuppo...

Last updated 20th November 2021

[Walkingtall62]

Hi, thanks for that report. Very interesting

[Psmithuk]

So grateful to have this explained!

[Zia2]

Great explanation. Thankfully both of my labs have ANC and ALC listed on them. My own excel computes it too when I enter numbers into it. (I no longer do this since the CLL doc's staff have my labs listed in three different ways that I can view them now. The "graphs" not numbers is what i like the most). Thanks Neil

[albie58]

Great explanation! Thank you!

[Schubert1870]

Thank you so much for the informative post.

This will allay concerns when deciphering future blood tests.

[Sushibruno]

What is considered a high absolute count? I know that doubling is what's important but I like to know if I'm making sense🤣 .I feel like the student that's lost in her class🤣

[AussieNeil Partner Administrator in reply to Sushibruno]

I'm using the typical US lab lymphocyte counts below, where the normal lymphocyte count is around 2,000. In most other countries that would be a count of around 2.0.

I'd tend to consider 'high" when talking CLL, more like height, rather than blood pressure, that is, it's more of an observation than an indication of potential health concerns*. High counts are rarely a problem, because CLL cells aren't sticky and are only a tiny bit bigger than red blood cells, (which is only because red blood cells lose their DNA), so CLL cells aren't likely to block small capillaries or otherwise cause blood circulation problems.

When your lymphocyte count gets to around 4,000,000, you'd have around 1 CLL cell for every red blood cell in your blood. The highest lymphocyte count I've heard of with CLL is 1,400,000. We have members who have mentioned having counts in the 500,000 to 800,000 region. I chose lymphocyte counts above 30,000 in my example above, because CLL specialists only really begin to take an interest in doubling time when the lymphocyte count exceeds 30,000.

*I guess I consider above 100,000 high, but it really depends on the context. If you are going to be treated with a very fast acting drug like Venetoclax, above 25,000 would be considered high enough to put into place a protocol to manage the potential risk of tumour lysis syndrome, but the absolute lymphocyte count isn't really a consideration until treatment is initiated.

Neil

[Sushibruno in reply to AussieNeil]

😁thanks Neil.

[Sushibruno in reply to AussieNeil]

thanks for the reminder Neil, I take it that im likely to get TLS with a Alc of 278k? My numbers are out of wack.

[AussieNeil Partner Administrator in reply to Sushibruno]

No, you might be a likely candidate for TLS if your doctor doesn't follow the protocol for assessing your TLS risk for your chosen treatment and putting you on allopurinol if needed and monitoring your blood counts when you are at most risk, to see if any further support is needed. I'm certain that Dr Lamanna would do that. Please leave your care to Dr Lamanna - that's her job! If you have any particular concerns that you read about, ask her when you discuss your choice of treatment.

I was probably a risk for TLS before I began treatment, because I had a rather swollen spleen and some enlarged nodes. A month of acalabrutinib followed by obinutuzumab infusions reduced my tumour burden sufficiently, so that I didn't need to go to hospital during my venetoclax ramp-up, when I would have been at most risk of TLS.

TLS can happen when you have a large tumour burden and you kill it off way too fast for your body to manage the recycling tasks from all the dead CLL cells.

Neil

[Sushibruno in reply to AussieNeil]

thanks Neil, I'm getting ready for Tuesday that's why im here to get an idea of what to ask. Yes dr. Lamanna is the expert and i trust her like i never trusted a doctor. Im just plain paranoid.

[AussieNeil Partner Administrator in reply to Sushibruno]

If you start on acalabrutinib or another BTK, you might see your lymphocyte count temporarily climb to 600 to 700 before they die. We've had some other members report that happening. Won't it be good to see all your CLL cells being flushed out and dying off?