smudge cells? What does it mean? High potassium from white blood cells?

[Createdpath]

does anyone else have high potassium? I was told to drink 100 oz of water daily isn’t that too much water?

Also what are smudge cells?

[Jm954 Administrator]

Smudge cells are just your CLL cells seen on a blood smear that have broken up with the mechanical forces of making the smear, nothing to be concerned about. Some people have tried to link the incidence of smear cells to various CLL features but there's no correlation.The photo shows smudge cells on the left and intact CLL cells on the right.

100oz of water is almost 3 litres and a reasonable amount to drink each day. I find it's easily doable if I try to drink 33oz morning then again in the afternoon and again in the evening.

cll cells

[AussieNeil Partner Administrator]

CLL cells have weaker membranes than healthy B cells. That's why they easily break in a blood smear and are noted as smudge cells. Having them is a good prognostic indicator. If you had a high absolute lymphocyte count and/or enough of them smudged, then that might explain the high potassium.

100 ounces is about 2. 8 litres. How much you fluid need to drink (and that includes fluids other than water) depends on how active you are, the temperature and what treatment drugs you are on. You should drink enough do that your urine is light straw in colour. If you are putting on weight, you are drinking too much fluid.

Neil

[Shrink in reply to AussieNeil]

Neil , Why are Smudge cells good prognostic indicator ? Best Regards ,

Cyn

[AussieNeil Partner Administrator in reply to Shrink]

Percentage of Smudge Cells on Routine Blood Smear Predicts Survival in Chronic Lymphocytic Leukemia

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

The first suggestion that smudge cells may be biologically significant came from two intriguing observations in the 1950s demonstrating that smudge cell percentage was independent from the degree of lymphocytosis and seemed to be patient specific.23 We recently confirmed these two observations and demonstrated that the percentage of smudge cells remains constant over time in any given CLL patient.13 We also demonstrated that smudge cell formation is inversely correlated with CLL B cell content of vimentin, a cytoskeletal protein critical for rigidity and integrity of lymphocytes. The physiologic role of vimentin may extend beyond maintaining cell integrity; rearrangement of vimentin fibers was shown to participate in cell activation and signal transduction.25 High vimentin expression has been shown to be associated with poor prognosis and metastatic potential in breast26,27 and colon cancer.28

Because the percentage of smudge cells inversely correlates with vimentin expression,13 we hypothesized that the calculated smudge cell percentage on a blood smear would have prognostic value in CLL. Accordingly, patients with low vimentin expression would have a high percentage of smudge cells and a better prognosis, whereas those with high vimentin expression would have a low percentage of smudge cells and a worse prognosis.

:

In the current study, we demonstrate that a low percentage of smudge cells predicts shortened OS as both a continuous and categoric variable in an independent sample of CLL patients participating in a prospective observational cohort study. The percentage of smudge cells was lower in high-risk patients as defined by Zap70 and CD38 expression and 13q deletion; however, there was only weak correlation between Zap70 and CD38 expression as a continuous variable and smudge cell percentage. The lack of strong association of smudge cell percentage with other prognostic factors suggests a distinct role for the cytoskeleton in CLL biology. The latter notion is further supported by the fact that, in multivariate analysis, the percentage of smudge cells was an independent predictor of OS.

[Shrink in reply to AussieNeil]

Thank u Neil. Always !

[Lavinia-Blue in reply to AussieNeil]

I have smudge cells, but unfortunately the test results do not report percentage, only that they are “marked.” I wonder too, if after treatment/therapy the smudge cells decrease, as the treatments would likely wipe them out being that they are the weakest and will go first.?

[AussieNeil Partner Administrator in reply to Lavinia-Blue]

Good question! Given smudge cells are commonly seen in CLL, then yes, as the CLL tumour is reduced in the blood, the incidence of smudge cells should reduce. With BTKi drugs working the way they do in releasing the binding mechanism that keeps CLL cells in the nodes, spleen and bone marrow, so the CLL cells move into blood, you are likely to see smudge cells mentioned for quite a while into treatment. They shouldn't be noted when the absolute lymphocyte count returns to within the reference range.

Looking back at my blood test records, I noted that smudge cells were recorded as being present fairly often up until I started treatment and no mention of them since .

Neil

[Lavinia-Blue in reply to AussieNeil]

Yes, I am wondering if the smudge cells are wiped out completely. So, the weakest CLL cells are gone after treatment and one is left with the hardier cells. As you say, no mention of them since treatment. Like the very, very few cases of IGHV mutated folks going unmutated after treatment.

I will have to keep my eye on this.

[AussieNeil Partner Administrator in reply to Lavinia-Blue]

The CLL IGHV mutation status is most unlikely to change.

[Lavinia-Blue in reply to AussieNeil]

I have read an article a while back and do not have the reference to the article right off hand, but I do have the chart of some folks changing IGHV status following treatment, with two no treatments.

IGHV status following treatment chart.

[AussieNeil Partner Administrator in reply to Lavinia-Blue]

Thanks for finding that interesting paper from which you presented table 1:-

Change in IgHV Mutational Status of CLL Suggests Origin From Multiple Clones

sciencedirect.com/science/a...

Abstract - Background (with my emphasis)

Fluorescence in situ hybridization and immunoglobulin (Ig) heavy-chain variable-region (IgHV) mutational status are used to predict outcome in chronic lymphocytic leukemia (CLL). Although DNA aberrations change over time, IgHV sequences and mutational status are considered stable.

:

Abstract - Conclusion

The existence of these new nonplausible heavy-chain variable regions suggests either the CLL cancer stem-cell maintains the ability to rearrange a previously silenced IgH allele or more likely that the cancer stem-cell produced at least 2 subclones, suggesting that the CLL cancer stem cell exists before the process of allelic exclusion occurs.

Conclusion

The changes in IgHV sequence and mutational status with constant marker chromosomes observed in this series suggests multiple leukemic subclones might be present early in the disease process. Two (patient 3 and patient 4) of the 7 patients began expressing a biologically nonplausible VH region—a region previously deleted from the functional chromosome. Primary laboratory error including incorrect collection or improper IgHV sequence analysis needs to be considered. However, because the...

I don't have access to the full article, so I don't know what follows, but the prior sentence is indeed a likely reason for the expression of a biological nonplausible VH region. IGHV mutation testing is difficult to do correctly and there has been an international program running for a few years to get laboratories doing this test to follow an agreed standard process. It has always been considered possible that a very small percent of those with CLL could have their IGHV mutation status change and indeed having two unrelated clones is one way for that change to occur, but it would be very rare.

Neil

[AussieNeil Partner Administrator]

The paper I quoted explains all this: ncbi.nlm.nih.gov/pmc/articl... Note it states "Other prognostic factors, including IgVH mutational status, Zap70 and CD38 expression, and cytogenetic abnormalities detected by FISH, were also characterized in this cohort, allowing us to investigate the relationship between these factors and the percentage of smudge cells."

Note that this 2009 Mayo Clinic paper was done back when there was a lot of research trying to find faster and cheaper than the at the time, difficult to do reliably IGHV mutation testing. Interestingly, there was an independent paper done in Egypt in 2018 that :

sciencedirect.com/science/a... This paper observed;

Correlation studies with other prognostic factors revealed that lower Smear cell percentage was highly significantly associated with CD38 expression, short lymphocyte doubling time (LDT), the presence of cytogenetic abnormalities, ATM and P53 deletions (p < .05). However, no correlation was reported with trisomy 12 (P > .05) (table 6).

It concluded; In Conclusion, our data indicate that low percentage of smudge cells (<30%) could be considered as an adverse prognostic predictor being associated with high risk prognostic markers. Because minimal technical resources are required, the estimation of smudge cells percentage is a potential, universally available, and applicable prognostic marker. It should be considered in an optimal prognostic stratification of CLL patients. Future studies directed towards elucidating the role of vimentin in various signaling pathways would open up new approaches for the biology of this disease and the development of new therapeutic targets.

Have a read and let me know if you need any clarification.

Perhaps if you show your doctor or specialist the papers, they can ask your pathology lab to do a manual count of smudge cells as a percentage of lymphocytes.

Neil

[LeoPa]

All liquids count,not only water. Drink enough to have light yellow urine. Neither dark nor white.

[Smakwater in reply to LeoPa]

All appropriate relative liquids count. E.g, alcohol or other dehydrating solutions such as those containing high levels of alkaloids and sodium.

[LeoPa in reply to Smakwater]

Yes, that's why it's best to go by an objective measure.

[janvog]

There are some that consider drinking "warm" water to be beneficial for health. "Warm" water is the ONLY liquid which I drink since decades because I always felt "shocked" by cold liquid. Even during the night, due to dry mouth from CPAP, I sip warm water which I keep in a glass bottle sitting in a cup sitting on a cup warmer. What is known about any virtue of "warm" water ?

[Islandvibes in reply to janvog]

Thanks for tip