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Questions submitted by readers and answered by the CLL Society Medical Advisory Board
By Susan Leclair
My blood work is showing something called variant lymphocyte and prolymphocytes. This showed up right after my second FISH test showing a 3rd chromosome del adding 17p- TP53 to my 11q-/22,23 ATM and 13q. I was told it was an evolution even though I have never had treatment. Also, something called white cell fragility (cell lycing?) Where would you go for a second opinion?
When they work correctly, lymphocytes are the cells responsible for your immune system. They begin their lives as lymphoblasts, then go through a series of maturation steps which cannot be distinguished one from the other when using the common staining method in the CBC. Thus, they are all lumped together as “prolymphocytes”. The mature looking cells are then called lymphocytes. Functionally these cells can be separated by the use of an instrument called a flow cytometer.
All leukemias begin by damage to the DNA. Once it is damaged, DNA can become unstable. This instability then can create even more damage. For example – and forgive me for the type of examples I use, some of the time they are a bit of a stretch. Dirt on a hill is simply dirt. Add a little water and plants grow and the hill becomes stable. But dirt subjected to 10 inches of rain, while still remaining dirt, can rip out plants and become unstable. Once that has happened, that dirt can become a mudslide with only a little rain. This is what happens in leukemia. A beginning DNA damage can allow additional damage to happen. This is the evolution of which they speak. IN your situation, they can prove which mutations are causing this evolution.
Just like the dirt analogy with rained soaked dirt affecting the plants, once DNA becomes damaged, it affects the rest of the cell. In CLL, one of the most common sights are cells that has been ruptured during the specimen collection and testing process. They are sometimes reported as “smudged cells” since that is probably what happened to them during the testing.
I noticed my absolute lymphocyte counts and my hemoglobin and other values in my CBC can vary quite a lot from the tests done by my community hematologist and those labs done at a different lab at the referral center.
Whose results should I trust? Should I worry about the fluctuations?
This is a very common question in today’s world. Let’s divide the testing issue into three parts –
- What happens to the patient prior to the blood specimen being collected.
- How was it collected and transported to the testing site.
- What testing is performed and are there variations among different sites.
- How do the provider and patient interpret the results.
The first part is called the pre-analytical phase of testing. You want to be in the same condition and have the collection performed at the same time and in the same manner to enhance precision. For example, hemoglobin and hematocrit values change up to 15% during the day. So, if those two values are important to you, you should always have the blood collection approximately at the same time. Typically, values are higher in the morning and decrease as the day goes along. This means that if your first specimen was drawn at 8 o’clock in the morning and your hemoglobin was 14.0, a second specimen taken at 4 o’clock in the afternoon could have a hemoglobin value of 11.0-12.
White cell counts are also affected by external and internal issues. And, in many situations, these variations will change throughout the day. For example, want to increase your granulocyte count? Do some exercise prior to having the blood collected. The granulocytes which attach themselves to the inner walls of the blood vessels will be shaken off and increase the number of cells counted. Lymphocytes have a more consistent number, but they too can be influenced by changes in adrenaline (stress, fear, etc.) or by exposure to various things like a cold virus or by any trauma (bruises, bug bites and the like).
Then come collection. The most variable collection method is the capillary puncture or fingerstick. Here you are not getting blood but a mixture of blood and cells and other fluids. Since there is no way to regulate the mixture, it is very difficult to compare this set of values with the last set.
Then come the length of time that the tourniquet is on, the speed with which the blood is taken up into the test tube, the proportion of blood and anticoagulant, how well the blood and anticoagulant were mixed together (too violent you get hemolysis – too slight and clotting can occur in the test tube).
I am going to assume that both sites perform the test on site; otherwise we would need to get into transport criteria.
Now for the analytical issues.
There are about a dozen different instrument manufacturers making multi-channel hematology instruments. Each has some advantages that the others do not. One would expect to see some variation simply due to the processing in the instrument. If one wanted an instrument that was highly sensitive to platelets, then one might have to accept a slightly less accurate MCV or some other test. Another example but this time in chemistry. Do you want a blood glucose test that is accurate to the 4th decimal place? If you do, then you will have to settle for a 15-minute wait once the sample is placed in the instrument. Or do you want a lesser accuracy in order to get a fast result?
A side note – Most instruments are well maintained but some are older than others. With age comes a loss in quality.
Then there is the post-analytical issue.
At the core are these values so different that they cause a change in interpretation? Again, would you really mind that your totally accurate hemoglobin is 14.0g/dL and your result is 14.1? Or would you mind if your absolute lymphocytes should be 5.5 and the instrument said it was 6.0? Obviously if the values were 5.0 and 15.0, then you have a big concern, but if the value difference is small, it is usually not significant.
Who should you trust? Your physician. Ask him/her to explain these differences to you. It may be that you will get an explanation that sounds like, “Well, I know that there can be some differences but, as long as they remain small, I use them as indicators, not exact values”.
In watch and wait the typical blood work numbers that get focused on are hemoglobin, neutrophils, lymphocytes, and platelets. Recently the monocytes numbers have crept upward. Would like to learn more about monocytes.
Monocytes are phagocytes, that is, their prime action is to remove dead and dying “your” cells as well as anything that is foreign (think particles from air pollution or a virus). They do most of their work in the tissues and use the blood stream as a mean of rapid transport from one place to another. So, when they bounce up, one has to first look back over the past 48 hours and determine, what have you come in contact with? A bruise? A virus? An abraded gum line? A paper cut? Air pollution? etc. There are also many medications that cause monocytes to come out of the tissues into the blood stream.
For people with CLL, all of those exposures can cause an exaggerated response. And, since monocytes are part of the immune system, they can sometimes be stimulated by the CLL cell’s actions. How to tell the difference is hard. You need to be very detailed about the recent past and then see if the absolute increase comes and goes or is in a steady increase that lasts for at least 3 separate CBC results.
Susan Leclair is Chancellor Projessor Emerita at the University of Massachusetts Dartmouth; Senior Scientist, at Forensic DNA Associates; and Moderator and Speaker, PatientPower.info – an electronic resource for patients and health care providers.
Originally published in The CLL Tribune Q3 2018.