What does CD 38 indicates?

[Nour80Leen2011]

My CD 38 = 5% what does it mean? And how can I know if I am muted or unmuted? Thanks a lot

Firas

[Hidden]

If you are CD38 (one of many "Cluster Differentials...basically a molecule) and ZAP70 positive you are assumed to be unmutated. Those are considered less favorable markers. I am unsure at what percentage you are "positive" or "negative".

These are determined by Flow cytometry test and do not actually test to see if you are IGHV mutated. They are used as a proxy which shows probably. Being mutated IGHV is considered better.

The CD38 molecule seems related to CLL cell survival and interferes with Apoptosis (cell death) although I read about all that last year and might be off some.

Scott

[Ironj]

I just got my results to tell if I was Mutated. The test was a Bone Marrow Biopsy test was looking at the IGVH. That’s about all I know, you’ll get much better answer to follow from others on the site that can explain in detail. Best wishes John

[Hidden]

I looked it up, under 30% is considered negative.

[Nour80Leen2011 in reply to Hidden]

Thanks dear

[Newdawn Administrator]

This is a very good explanation from a reliable source (the originating link is no longer operative);

CD 38 & ZAP 70

What is the significance of CD38 in CLL?

The presence of the antigen CD38 on B-CLL cells is a much discussed prognostic indicator in CLL. Whether it is a truly independent prognostic indicator or simply a reflection of IgVH gene mutational status, CD38 clearly seems to have some relevance in predicting whether a patient’s CLL is likely to have a favorable or unfavorable clinical course. CD38 is detected by flow cytometry, a diagnostic technique frequently used in confirming CLL.

Patients with less than 30 percent CD38+ B-CLL cells are likely to have a favorable clinical course requiring minimal or no therapy. Patients with equal to or greater than 30 percent CD38+ B-CLL cells are more likely to have an unfavorable clinical course requiring earlier and ongoing treatment. Significant differences in survival are also thought to exist between these two groups. CD38 expression remains stable over time in the majority of patients, but it is known to change in approximately 25 percent of cases. Its level of expression does not seem to be influenced by chemotherapy.

The connection between CD38 expression and IgVH gene mutational status is not well understood. It appears that patients with less that 30 percent CD38+ B-CLL cells are likely to have mutated IgVH genes while patients with greater than 30 percent+ B-CLL cells are more likely to have unmutated IgVH genes. While this is often the case, there is approximately a 30 percent discordance between assays for CD38 and IgVH mutational status (see also: What is the significance of IgVHgene mutational status in CLL?)

Both CD38 and IgVH gene mutation are thought to be useful prognostic indicators in B-CLL, but because of the relative ease of testing for CD38, it is a much more convenient test.

CD38 and IgVH mutational status are just two of a number of prognostic indicators in CLL. Others include, circulating levels of beta-2-microglobulin and soluble CD23, lymphocyte doubling time, serum thymidine kinase levels, bone marrow histology, and chromosome abnormalities.

What is the significance of ZAP-70 in CLL?

ZAP-70 is an abbreviation for Zeta-chain-associated protein kinase 70. This protein is a member of the protein-tyrosine kinase family and when expressed on B-CLL cells is surrogate marker for IgVH gene mutational status. The presence of ZAP-70 can be detected by flow-cytometric analysis, and the level of expression is thought to correlate with mutational status.

CLL patients with less than 20 percent ZAP-70 positive B-CLL cells are likely to have mutated immunoglobulin V genes, predictive of a more favorable clinical course, while patients with greater than 20 percent positive B-CLL cells are likely to have unmutated immunoglobulin V genes, predictive of a less favorable clinical course.

Hope this helps. Best wishes,

Newdawn

[albie58 in reply to Newdawn]

Newdawn....can your beta-2 change throughout your disease?

[Newdawn Administrator in reply to albie58]

My understanding is it can Albie and influenced greatly by tumour burden. It’s not a test that seems to be routinely carried out despite being an important clinical indicator. This HU discussion from some years ago may help you because there’s experiential accounts but some of the links within it are now defunct;

healthunlocked.com/cllsuppo....

Newdawn

[caven in reply to Newdawn]

30% is the level for identifying an ‘adverse finding’ as indicated by NewDawn ~ so, the lower the percentage the better it is for the CLL-person!

“With regard to clinical outcome, progression-free survival was significantly longer (75% versus 37% at 5 years; P = .00006) in patients with lower CD38+ B-cell percentages.” (See: Blood, 2001 98:2633-2639; doi: doi.org/10.1182/blood.V98.9....

CD38 is a protein antigen marker attached to the outside of leukemia cells ~ i.e., the B-cell Receptor, BCR. "The presence of an elevated CD38 suggests a faster progression “...but "scientists still do not completely understand why CD38 plays a role in CLL/SLL.”

Caven

[Cllcanada Top Poster CURE Hero in reply to caven]

Simply..CD38 is a surrogate marker for IGHV gene mutation. There is a 30% tipping point.. below the 30% you would be IGHV mutated. If well above then unmutated...

Mutated generally have an indolent, slow moving disease. This has been used for 15 years, and has proven to have over 70% accuracy.

~chris

[albie58]

Thank you!!

[JR1964]

As in talking with Dr. Weirda at MDA. I asked him about the CD38 expression. His answer was that he was not concerned about it and that it was not going to be a factor for him to decide anything in the course of treatment. CD38 or ZAP70 to him were unreliable in deciding a patient's condition or treatment for that matter. As well as he added the whole treatment landscape is changing so drastically that what holds true today - not so tomorrow. With the upcoming treatments coming all walls that were once impregnable are now crumbling. AND BELIEVE- THE CURE IS COMING- HAVE FAITH- STAY STRONG J.R.

[AussieNeil Partner Administrator in reply to JR1964]

But for those outside of the USA or without access to accurate IgHV testing, CD38 and sometimes ZAP-70 are available in the Flow Cytometry CLL diagnostic report. Knowing with around 70% accuracy that you are likely unmutated (i.e. CD38 and ZAP-70 positive) is rather important when you are facing treatment and it's hard to get non chemo treatment...

[JR1964 in reply to AussieNeil]

It is unfortunate for ones outside the U.S. not to have access to what in the U.S. we have. I ask many questions of Dr. Weirda and his team. As well as Dr. Keating and such. I take it for granted. But in talking with both, everything is changing. With all the treatments unmutated vs mutated has become much of the same level of playing field. It comes down to which treatment is the best from all the testing. But even with the advance testing done here, there are still instances such as a friend of mine. Given FCR and not knowing is markers and such. Becoming quite ill. But insisting to stay with a Oncologist in the area who is not a CLL Specialist. That does not do the specialize testing. And MDA only being 35 minutes away. Very frustrating. STAY STRONG J.R.

[SeymourB in reply to AussieNeil]

I've read that Australia doesn't have many labs doing IGHV testing, and that it has been expensive there. I wonder how much it costs now, and how the cost varies country to country.

As far as the whether CD38 or ZAP70 are a good substitute, I have my usual long story to tell.

My initial results in February, 2011, ordered by a general oncologist showed:

12.52% CD38+ - Immunophenotypic Analysis, CD38 expression is not detected. Lack of CD38 expression in B cell chronic lymphocytic leukemia (CLL) is associated with a more favorable outcome.

So, 12% is considered "not expressed." Cool. I didn't like the oncologist, and found a hematologist/oncologist, who ordered additional tests in April, 2011, which showed:

70% of the lymphocytes are CD19 positive and 14% of the selected lymphocytes express ZAP70 with CD19. Therefore, 20% of the B-Cells (CD19 positive) are ZAP70 positive. Our Data shows that patients with >/= 10% ZAP70 positive cells have more aggressive disease. Positivity for ZAP70 in the leukemic cells in patients with CLL usually, but not always, correlates with more aggressive disease, unmutated IgVH, and positivity for CD38. Negativity or ZAP-70 does not always rule out unmutated IgVH or aggressive disease. We strongly recommend correlation with IgVH mutation..

So I was really worried about the 20% ZAP70 result. I need to review the paper copy of that test result to see if CD38 was even reported.

I read articles by Chaya Venkat on clltopics.org that urged getting an actual IGHV test because CD38 and ZAP70 are not very reliable. In March, 2013, I finally got that test:

IgVH Mutation Status - Mutated, VH3-7 family

IgVH Mutation Rate - 15.44%

In 2016, CD38 came back as 2%, negative.

So the ZAP70 was not a reliable proxy for IGHV mutation status for me. In other places, I've read similar things.

ncbi.nlm.nih.gov/pmc/articl... - see Table 1.

Terry Hamblin commented on the IGVH (IGHV) test in his blog in 2010 ( mutated-unmuated.blogspot.c... )

"First, it is a matter of expense. The test costs $200 to do, though commercial labs charge $1000. You can get it done and interpreted in England for $200 plus the cost of the blood draw and a courier. Set next to the cost of one course of fludarabine let alone rituximab, this is peanuts."

I've had quite a few tests that were priced over $1000, though the gangster deals that U.S. pharmacies make with the insurance company lowers the actual cost considerably. Someday, I'll write it all up.

What I learned from all this is:

1. Test results can lead to significant emotional strain.

2. You often can't really compare tests done by different labs.

3. 12.52% looks so exact. It's not. Don't let precision-looking readings fool you into thinking they are accurate. It's almost criminal for a lab to give a reading without a range of certainty.

4. For me, the IGHV status seemed to go along with CD38, but not with ZAP70. I bet there's someone reading this who experienced the opposite.

5. New prognostic indicators are discovered every year, it seems. No single test result can give you a prognosis. A good prognosis requires a number of tests, examinations by qualified specialists, and takes into account age and other health issues.

6. In the U.S., and possibly elsewhere, one must ask for tests, and not wait for the doctor to decide what's best if they are not a CLL specialist. Almost every expert now says that IGHV is a mandatory test for CLL prognosis.

7. Biochemists really confused me by renaming the gene from IGVH to IGHV right around 2010.

8. When you get a good prognostic result - focus on it. Stare at it. Cherish it. Share it with people. Try not to let the bad prognostic results take over your life. Hope is powerful medicine.

=seymour=

[SeymourB]

Firas -

Based on my own experience, and many things I've read, that CD38 result should give you some hope.

Best wishes,

=seymour=

[ThreeWs]

Hi Nour...,

Keep in mind that CD38 is only one data point in the complex puzzle that is anyone's CLL. The percent of CD38 expressed from your report is low and is not something to be alarmed about.

Your post has expanded the "marker" CD38 issue to include much discussion about ZAP-70 for which I wrote a patient perspective article in the CLL Society Tribune. The uncertainty surrounding the accuracy and meaning of ZAP-70 makes it doubtful as to how useful the test is for us patients. I say this in spite of my being educated through ZAP-70 study to the important concept of directed therapy to target the aberrant signaling which drives CLL.

ZAP-70 is a rabbit-hole that can be educational and fascinating to glimpse what goes on in a slice of the CLL puzzle.

For those interested: Read the article "CLL Markers and What They Mean – A Patient Perspective – Part I – ZAP-70 | CLL Society" Click the link - cllsociety.org/2018/03/cll-...

Criticisms welcomed,

WWW