CD 38 positivity issues

[Vlaminck]

Hey, all, it is from this forum that I first came across mention of someone being "CD38 negative.' Read a bit more since then. I've been on W&W for almost 2 years, doc initially rated me at zero, am mutated, and he's mentioned a couple of other good things. He's never mentioned CD38, but checking my Flow cytometry thanks to seeing mention here, I am clearly positive -- 20 or so.

I know CD38 is not good. But does anyone know whether this impacts treatment, for example, special treatment for CD38 possibly (like treatment for her2 positive in breast cancer perhaps)? Has anyone else been positive and seen the level go down, as I understand that Flow cytometry can change over time.

Any other significance other than, well, bad to share about this issue?

Thanks in advance

Deborah

[AussieNeil Partner Administrator]

Hi Deborah,

This is probably not an issue for you, given you live in the USA. Also, what you are missing is the historical context of CD38 (and ZAP-70) testing. When it was discovered that CLL could almost be considered to be two different leukaemias/lymphomas, depending on IGHV mutation status, the challenges of reliably performing this test became an issue. It was also costly. IGHV unmutated folk typically had a short time to treatment after diagnosis and on the chemo drugs available back then, typically had a shorter remission time compared to those who were IGHV mutated. Then it was found that if you were IGHV mutated, FCR treatment gave very long remissions. So with the arrival of targeted 'non-chemo' treatments for CLL, it was important to ensure that FCR and other older chemo treatments were not given to those who were IGHV unmutated if these newer, 'non-chemo' treatments were available.

So for a few years there was a great deal of research into finding cheaper, hopefully more reliable ways of determining IGHV mutation status. From that research it was determined that being CD38 negative and ZAP-70 negative correlated with around a 60% chance of being IGHV mutated. The correlation isn't perfect, so it is quite possible to be CD38 positive, like you and still be IGHV mutated. (ZAP-70 is even less reliable than CD38 in predicting IGHV mutation status, plus CD38 and ZAP-70 results can change over time. IGHV mutation status rarely changes, and when it does, most often that would be due to the challenge of reliably testing it.)

In the USA, FCR is only recommended by some CLL specialists, if they consider that the ~55% chance of achieving a 'cure' is worth the longer term risks associated with FCR, for which you also ideally to be under 65. Only about 10% of those with CLL fall in that category. In summary, if you get to the stage of needing treatment and your specialist recommends FCR, that would be a good time to ask them about your CD38 positive result, IF the 55% chance of a cure appealed to you. If you are offered another chemo treatment, BR or chlorambucil, ask for a second opinion!

Neil

[johnl]

It's been a while, but if I remember correctly the cut off percentage for CD38 positive/negative is around 30%. So if your 20% cd38 your negative.

I also remember that CD38 percentages changes about 25% of the time.

john

[AussieNeil Partner Administrator in reply to johnl]

Different studies have identified different dichotomous cut-off points for labeling expression as positive or negative, most commonly 20% [4] or 30% [3], while others have recommended that levels as low as 7% may be associated with a poorer prognosis[5].

tandfonline.com/doi/pdf/10....

[Vlaminck in reply to AussieNeil]

Thanks so much, Neil and John. That's all interesting -- and my education grows constantly from this website. I like that the CD38 can change over time (hopefully can go down? and not just up) -- In reading about CD38, I see the main reason it's a bad marker is because it tends to reduce NAD. That led me to read about NAD, and I'm now going to target increasing my NAD to counter it with diet and supplements (hey, can't hurt, right?) plus continuing my other phytonutrients which already help with NAD, esp. green tea, and curcumin. (Started doing like you, Neil, and some days green tea, others curcumin --I think I read somewhere that that was your protocol)