CD38 POSITIVE AND ZAP -70 POSITIVE : New to this... - CLL Support

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CD38 POSITIVE AND ZAP -70 POSITIVE

Ladydi49 profile image
17 Replies

New to this forum but not new to CLL as I was diagnosed in Sept of '07 and so far no treatment but rather watch and wait. I was recently reviewing my flow cytometry from Sept of '07 and saw that I'm CD38 POSITIVE AND ZAP-70 POSITIVE so, I Googled it and it scares me! The article was suggesting that people who test positive with these 2 markers don't do as well? Does anybody else have this and does anybody know if it's true regarding good vs poor outcome? I also just had (3) days ago the first of 3 ivig infusions as my IGg is low and because I have been unable to fight off a sinusitis/bronchitis infection that started 7 weeks ago. So far I haven't had any side effects from it. Wishing everyone the best, Dianne

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Newdawn profile image
NewdawnAdministrator

Hi Dianne and welcome.

The first thing that occurs to me is you’re 10 years in and still on W&W so certainly not a poor clinical course so far! I’m not sure what Google reports you’ve been reading but some are dated and a bit grim without taking into account the massive impact the new novel treatments are having on CLL, particularly those who have an unmutated status which you seem to be suggesting you have. Has your specialist ever confirmed your IgVH mutuational status because as you’ll read from this very informative information, much depends on percentages of CD38. You’re certainly bucking the trend at the moment which is more unusual in patients who are unmutated.

‘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.’

cllfaq.info/ddpot.html#cd38

Best wishes,

Newdawn

Cllcanada profile image
CllcanadaTop Poster CURE Hero in reply to Newdawn

Newdawn... CLLFAQ is now off line, so the link is no longer available, as a reference. It's a sad loss.

~chris

Newdawn profile image
NewdawnAdministrator in reply to Cllcanada

Yes I realise that Chris and I appreciate sadly why. I included it only as reference to original respected source but meant to mention it’s no longer online (which is why I included the whole text instead of just the link).

Thanks Chris,

Newdawn

DebLeeCox profile image
DebLeeCox in reply to Newdawn

Hi Newdawn, quick question can on be CD38 and Zap70 negative but still be unmutated? And if this is the case what does it mean for prognosis? Thanks Deb

Newdawn profile image
NewdawnAdministrator in reply to DebLeeCox

Hi Deb,

Oh boy this isn’t such an easy question to answer and I’m relying on the more advanced ‘boffins’ to chime in here because even the article says;

‘The connection between CD38 expression and IgVH gene mutational status is not well understood.’

My understanding, even though it must be remembered that there is a ‘30 percent discordance between assays for CD38 and IgVH mutational status’ (which means they don’t always get it right), is that presently the 30 percent CD38+ B-CLL cell result is used diagnostically as an indicator of mutational status. My understanding therefore is that this will be the interpretation of mutational status based on these results. So in brief, the answer to your question would probably be no in relation to being negative for both CD38 and ZAP 70 but I’m not prepared to say that definitively.

However, it’s a complex area and this isn’t the whole story. As Professor Pettitt says in this excellent article;

‘Although many different things can predict outcome in CLL, it should be stressed that there is as yet no proof that knowledge of these things influences outcome in any way.’

cllsupport.org.uk/making-se...

‘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.’

The one certainty I’ve discovered about CLL is there’s no certainty which is why predicting outcomes and spooking people with predictions emanating from individual prognostic factors concerns me. Recently I had a pm from a member with a 17p deletion who was still treatment free and doing well after donkey’s years. There’s so many factors and it seems that the interplay between them is key. It’s such a heterogenous disease and becoming more scientifically understood weekly.

You’ll hear a lot about clinical outcomes for patients with an unmutated status and this relates to the observed less favourable response to FCR for the unmutated especially with associated adverse prognostic factors. However, the BTK inhibitors like Ibrutinib have been a game changer to some extent as this quote from Dr. Sharman indicates;

‘In contrast to the general themes of who does better / worse with chemo, it would appear that patientswith unmutated BCR / IgVH actually respond more quickly and deeply to ibrutinib.’

cll-nhl.com/2014/04/mutated...

Apologies it couldn’t be a quick answer but it’s immensely complex and others much more scientifically informed will be able to give you greater help.

The important thing is your discussion with your doctors particularly as it relates to treatment choices. In the U.K., IgVH mutational status isn’t routinely checked for and probably (certainly) not given as much clinical prominence as it perhaps should unless adverse chromosomal deletions are thrown into the pot.

Source the very best clinical advice you can.

Best wishes,

Newdawn

DebLeeCox profile image
DebLeeCox in reply to Newdawn

Thank you Newdawn, such a comprehensive answer you definitely answered my question, thank you! Appreciate it

Ezjacobs profile image
Ezjacobs in reply to Newdawn

Very very helpful explanation, new dawn! Thank you!

Suzieinwv profile image
Suzieinwv in reply to Newdawn

Your response is simply wonderful!!! Very informative & it gives me some hope. I was diagnosed around 6 weeks ago. I am CD38 positive & Zappa 70 test is borderline, which my specialist indicated that result is neither positive or negative. I am on W&W & staged at 0. I am still waiting on Fish result to find out if I’m mutated. I am going to save your response...as it’s a wealth of info.

Merry Christmas

Suzie

Ladydi49 profile image
Ladydi49 in reply to Newdawn

Thanks for the info...that being said, it's scary and there are times I hate having this disease. My hubby is a bury his head in the sand kind of guy and not very supportive especially if I'm talking about this disease probably because at my very first hematologist visit the doctor said to live my life...you won't die from this disease so that's all my hubby had to hear and why he doesn't want to hear truth/facts etc. That first doctor was right...I'll probably die from infection....

DebKat999 profile image
DebKat999

I just saw your post after writing my own first post. Seems that we are in somewhat similar situations with the very same concerns! All the best to you Dianne

Ladydi49 profile image
Ladydi49 in reply to DebKat999

Thanx and all the best to you too

MsLockYourPosts profile image
MsLockYourPostsPassed Volunteer

Dianne - you will reach a point of knowing which google sites are worth looking at, but for now stick to reliable resources like cllsociety.com and the sites listed on their home page. They have a good explanation of the basics as well as a glossary. When I was first diagnosed (2003) there were limited resources and everything I found googling said I'd be dead in five years. I'm still here!

Pat

Ladydi49 profile image
Ladydi49 in reply to MsLockYourPosts

Thanks Pat...as a nurse for 30 years I know too much and what is new to me I Google which I'll have to stop doing

seoul profile image
seoul in reply to MsLockYourPosts

And you will stay with us for another 25 years or more😏

seoul profile image
seoul

My test in 2013 before FCR was CD38 negative and ZAP 50%, but they told me, I am Unmutated.

Doing well since the end of FCR in 4/2014!

Seoul

Suzieinwv profile image
Suzieinwv

I am also CD38, and my Zappa 70 marker is Borderline, which means not positive or negative. I was recently diagnosed, placed on W&W and staged at 0. I am still waiting on Fish result to tell me if I’m mutated. Sigh...still trying to make sense of it all. Your 10 year wait before treatment Imho??? Sounds pretty good!

Take care,

Suzie

Ladydi49 profile image
Ladydi49

Thanks Susie...Wishing you the best, Dianne

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