Has anyone had their monocytes go up (above normal range) while on therapy, specifically acalabrutinib or venetoclax or both?
(Mine has creeped up over the past two months since I started venetoclax, don't know if any of these are related or just coincidence.)
Monocyte reference range for my lab is 0.2 to 0.8. I think the typical USA range is lower and tighter 300 to 500 (0.3 to 0.5 in my units).
Mine have been low - below the lower reference range, most of the 11 years before I started treatment, averaging 0.07. During treatment they averaged 0.14. After treatment, they are averaging just within the reference range at 0.21. I've had my highest results - up to 1.4, while on regular filgrastim (G-CSF) injections. None of my monocyte counts exceeded the upper limit during treatment (acalabrutinib + venetoclax + obinutuzumab. I don't think haematologists tend to get too concerned about high monocyte counts unless they are very high.
Per Chaya Venkat of CLL Topics/Updates fame, from whom I learned much of my early CLL knowledge;"Monocytes are the precursors of dendritic cells and macrophages – literally garbage monsters that can eat bacteria and other other pathogens alive. Dendritic cells are essential for alerting T-cells to the exact nature of the enemy.
Without dendritic cells telling them what to fight, T-cells are blind and unable to mount an effective attack strategy."
Neil
I started acalabrutinib in March and venetoclax on June 2 (6/2/22) with 6/13 being the 5th week of ramp up. Coincidentally, this is when the monocytes start to go up and it seems to be a trend. Don’t really know what is considered high for the monocytes. I did have a drop on 7/10, but I was in the hospital and dehydrated which I believe could have an effect on counts. I’m just hoping it’s not something like Chronic Myelomonocytic Leukemia.
I wouldn't be at all concerned with those results. It would be extremely rare to have a second blood cancer in the myeloid stem cell line (Lymphocytes and hence CLL are derived from the lymphoid stem cell line), plus you've only a few mildly high results - similar to mine in fact. The range should be provided on your lab test results, but it's not unusual to have the occasional result above the upper limit, particularly if you are responding to an infection.
Neil
PS good to see you tracking your results in a spreadsheet.
Thanks. I'll sleep better tonight. Could be a low-grade infection that is asymptomatic—fingers crossed. I believe I got the spreadsheet on the CLLsociety website.
I had elevated monocytes the year before last, for 8-10 months. They finally went back to normal. I am chalking it up to either I had something around stimulating macrophages, or perhaps my body wanted to make dendritic cells in response to something involving my T-cells. Or, somehow the machine read my odd CLL cells as monocytes. Since my CLL cells once briefly presented as blast cells, who knows.
My current lab abnormality since starting Venclexta is elevated bilirubin. It trends up....then down....then up again. Part of the downside to intensive monitoring IMO is that we now capture random trends like this, compared to once a year testing.
Lavinia-Blue -
I can't comment about monocytes and therapy. But I would say that hematologists lack any excitement for high monocyte values. I'm in watch and wait, and Dr. Thompson at M.D. Anderson was not concerned at all about my high absolute monocyte count, which was 6.68K/uL. Their normal range is 0.08K to 0.7K.
He said it's more common in Trisomy 12. It's been high for about 4 years now. I've indeed had flow cytometry to make sure that my lymphocytes, which are often activated lymphocytes that are larger than normal, are not being misread as monocytes.
Overall, I don't think they get excited about anything that's near the arbitrary low and high limits. It's not like someone has done a study that says, "All patients with cells slightly above or below normal immediately suffer the following adverse effects." So they wait till you turn green or get admitted for some other symptom. A sudden, dramatic spike receives more attention than a gradual change.
Monos vary throughout the day, as well. So getting your blood draws at the same time of day will help smooth circadian changes:
onlinelibrary.wiley.com/doi...
Effects of circadian variation, lifestyle and environment on hematological parameters: A narrative review
The upper and lower limits, BTW, are based on studies of various populations. Women differ from men. Fat people differ from skinny people. Asians differ from Africans. Populations within a country may vary due to economics or genetics. For example:
aidsrestherapy.biomedcentra...
Establishment of reference CD4+ T cell values for adult Indian population
"Results: The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/μL and for female population was 447-1846 cells/μL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/μL for Indian male population and 826-2997 cells/μL for female population."
Laboratory instrument manufacturers select a reference value for each cell type. Sometimes, that can be changed on the instrument, I believe.
The upper and lower limits are usually based on statistics seen in a population. The normal range is usually the center 2 quartiles of the population. Outside those 2 quartiles are the arbitrary abnormal levels. It would be somewhat different if statisticians had decided to use quintiles or sextiles for rough probability significance.
en.wikipedia.org/wiki/Quartile
The normal stats for Red Blood Cells, at least, are about a century old:
ashpublications.org/thehema...
Maxwell Myer Wintrobe: Influential Teacher in the Field of Hematology
"He realized that there were no published, reliable, normal blood values to use in clinical practice. He was the first to document statistically normal values in adults and children."
From his biography written by William N. Valentine, which I found on the National Academies Press web site, I found that he was researching the idea that anemia was more common in the southern U.S. than elsewhere. He based his normal values for red blood cells primarily on students:
"Wintrobe's careful observations made on Tulane medical students and women from Sophie Newcomb College—together with observations by Russell Haden in Cleveland, Edwin Osgood in Portland, and a few made in Europe— served as basic data for establishing normality in terms of quantitatively accurate observations. ...
Another important innovation came to Wintrobe in the middle of the night while puzzling over the inadequacies of the various indices then in vogue. These included color, volume, and saturation indices derived indirectly from ratios based on "percent of normal" for red cell numbers, hemoglobin content, etc. Wintrobe's method permitted direct calculation of the average cell size, MCV (mean corpuscular volume in cubic microns), MCH (mean hemoglobin
content in picograms), and MCHC (mean corpuscular hemoglobin concentration in percent)
—quantifications that are standard procedure in research and clinical laboratories today. "
If anyone is interested in Wintrobe's biography, please message me, and I can mail a PDF to you. After exploring the Tulane Medical School online archives for a class on the history of pandemics, I've become interested in the history of leukemia and medicine in general.
I hope this has been entertaining, and somewhat relieves anxiety.
=seymour=
Has anyone been on the combination therapy of Venetoclax, Ibrutinib and Obinutuzumab?
POST 4 - CAR-T cell therapy
Ultrasound Therapy for Inflammation 
V & O combination therapy
HG and platelet number for starting therapy
