New diagnosis DDX41 MDS-EB1: what made you start treatment?

Welcome @thick. There are a few other members in Connect who also have AML with the DDX41 mutation. Their stories and conversations are shared in a couple of different discussions. I'm away from my computer today and don't have access to my references. However, I'd like to tag members @sherbs @fortuitous and @asarnesejr (who already replied below).

From my understanding the DDX41 mutation has unique characteristics so it requires detailed attention. Mayo Clinic has some of the leading researchers for this genetic mutation. I had a bone marrow transplant 7 years ago (do not have the DDX41) but because of my involvement in Connect, my doctor and I discuss blood cancers. One of our chats was about DDX41 and how it isn't always the better option to go with a BMT. The discussion link posted below talks about that with members @sherbs and @fortuitous who both have sought 2nd opinions at Mayo Rochester.

AML with DDx41 mutation; Anyone else in the same boat?
https://connect.mayoclinic.org/discussion/aml-with-ddx41-mutation-anybody-else-in-the-same-boat/
There are numerous other conversations. If you type in DDX41 mutation in the top search bar you'll see a listing for all of the references.

AML is complex and can certainly be confusing. With 4 differing opinions that has to be making your head spin. I'd really recommend following through with the consult at Mayo Rochester if you're able. Mask up if you fly, there is an airport in Rochester with shuttle service to Mayo. Mayo also has free concierge services to help you with travel plans, lodging, etc. If you do schedule an appointment, our discussions in Connect cover a lot of bases so we'll talk you through all of it. You're not alone here. ☺️

Your situation sounds stable right now so you have time to make considerations. Do you have someone who would travel with you to Rochester?

Thank you, Lori -you are so helpful! I am starting to get the hang of this website haha. I appreciate all the other patients as well, and seeing that people are doing good who are further along on their journey.

I am just getting back results from another bone biopsy to see how I have progressed, and then will be meeting with my doctors in the next couple of weeks. That being said, what I have learned here about Mayo Rochester sounds amazing. I really would love to hear their opinion as well and will talk about possibly going there w my husband. I just wish it was closer and better timing since other close family members are having health issues too that makes the trip more difficult to plan.

Hi @lhick - it is not unusual with DDX41 MDS to watch and wait, but you also need to watch your blood counts - especially neutrophils and platelets. The latter looks on a low side for your blast %.

I was diagnosed with DDX41 AML (which most likely developed on the back on DDX41 MDS) - this happened 15 months before I actually started the treatment - such long period is highly unusual for AML. Germline DDX41-driven MDS/AML is typically very indolent and in some cases may take years to develop when some more aggressive AMLs may take only a few weeks.

It is probably unlikely that your blasts declined - most likely it is just slight variation in different parts of the marrow and accuracy of the tests. At the same time the fact that that the blasts are not growing is a further evidence of the indolent nature of your MDS.

Just as a side note, your germline variant R339 looks slightly unusual. You somatic one on the oyster hand is by far the most common somatic variant for DDX41.

Thank you for helping me and sharing what happened to you, igorp. I think it just shows that everyone's progression is different. Is there any reason you can think of why you may have stayed stable so long (like healthy diet, exercise, keeping stress down, support from loved ones, etc)? Can I ask what was the reason that you eventually started treatment - was it when you got to a certain blast percentage or when you got a certain mutation?

What you mentioned about my blasts declining is pretty much what my doctor was explaining to me yesterday, that the decrease is most likely due to sampling area. I understand that, and the fact that this mds isn't just going to suddenly go away. But, I also feel like if the change went the other way from 8% to 9-11%, the doctor would probably have said that I worsened instead of being stable... so I am still taking it as some sort of positive. Also, I got the rest of the results back, the DDX41 339 stayed at 49% and the DNMT3A mutation went from 8% to undetectable .. and the DDX41 525 went from 10% down to 3%. Again, this could have just been a difference within the sample taken as well I guess. Does anyone know if this is typical for mutation percentages to go down like this, or do they usually just keep increasing?

Hi There,

My story very much matches yours! I have a lot to share but may not be able to touch on everything in a single post.

Diagnosed with MDS in Aug 2024, DDX41 mutation (different mutation than yours but still in the DDX41 group), initial BMB showed 7% blasts. I felt fine - had fairly normal RBC and Hemoglobin, low WBC, and low platelets but nothing dangerously low.

My first medical team at Northwestern Medicine advised starting HMA as a bridge to immediate transplant. And, initially, I thought this was the road I would be traveling.

However, when I began to do research, I discovered quite a few papers that gave me significant concerns regarding this approach. These were not youtubers or fluff papers. These were published articles in medical journals indicating the opposite course of treatment - that DDX41 driven MDS is typically slow moving. Also that DDX41 patients seem to have a much more difficult time with SCT.

I told Northwestern that we were putting on the brakes and that I was going to seek another opinion. I sought a second opinion from Mayo Clinic. When I went to Rochester, they showed me some of the same papers I had read! Their advice on a course of action was MUCH more conservative than Northwestern and matched up with every piece of data I could gather on my own.

We did proceed with a 3 rounds of Inqovi - and since I've been watch and wait. I'm fortunate in that the variant of my DDX41 mutation is considered low risk. My blasts dropped due to the Inqovi treatments (<2% as of 6 months ago), and my blood counts are very much the same as they were two years ago... I feel fine and am grateful that I can very much continue living my life - at least for now.

You have some time here! Use it to your advantage and specifically seek out an opinion from Mayo Clinic regarding what your course of treatment should be. There are variants of DDX41 mutations that can lead quickly to AML. And there are many more variants of DDX41 that are considered 'indolent'. Mayo is really the only place that I think a DDX41 patient should consider getting advice from.

You need to know what you are dealing with and I'd only be comfortable with an opinion and guidance from the folks at Mayo. They have the data to back up their decisions. Northwestern did not at the time of my diagnosis (things have changed greatly there since then). It is very likely that trip to Mayo saved my life - or at the very least, saved this version of it.

I've also hooked up with a Naturopathic physician as well in the hopes that whatever small edge I can find in this fight will help delay any progression. Lots to say on this subject but might be worthy of a different post or private message. I do believe there is benefit in this area but that it is likely marginal.

What I will also tell you (as I've been very recently informed by both Mayo and NWM) is that DDX41 might be linked to other cancers as well. The evidence is very sparse but it is worth knowing... I've been advised to be very proactive about cancer screenings for all sorts of things - skin, prostate, colon, etc... You probably should too - but the folks at Mayo are the ones you need to seek out for that advice.

Hi @lhick I just wanted to make sure you’ve seen this excellent reply by @sherbs about their experience with the DDX41 mutation! Very detailed and informational.
https://connect.mayoclinic.org/comment/1646697/