Does anyone else have AML with ddx41 genetic mutation?

Hi @fortuitous, There’s another member in Connect (@sherbs)with the same DDX41 mutation only with MDS, not AML. I just wanted to make sure you saw their message to you. Here’s the link. https://connect.mayoclinic.org/comment/1188060/

How have you been doing since reducing your degogen and venclexta?

Following up on this after my meeting with my team at Mayo Rochester.

For anyone with DDX41, I can highly recommend getting an opinion from Mayo. There really isn't a better group out there that has familiarity with this relatively rare mutation. I learned that there are many sub-types of DDX41 mutations - some more serious than others. It is important to know what sub-type you have as it may indicate different course of action and/or different treatments.

There are no guarantees, of course, and this could still develop into AML requiring more aggressive treatment and even SCT at some point down the road.

However, Mayo did disagree with the approach taken by Northwestern Medicine and indicated that early transplant is probably not the best course of action. This approach agrees with all of the research I've done on DDX41. I'm not sure why Northwestern wanted to take such an aggressive approach to treatment - when I confronted them on their approach and provided links to the papers I've found, they certainly didn't sell me on why early SCT would be a good idea. They just kind of dismissed the literature as not being significant due to the small numbers of patients studied. There may be some truth to that concept but, for me, making decisions based on the best information available makes sense over ignoring it without good cause.

I'd advise anyone working with Northwestern Medicine to seek additional opinions - no matter your mutation(s).

Thank you for the update! I’d read about delayed SCT for DDX41 mutations and realized my hematologist/transplant/research specialist at Mayo was one of the authors of the study. Their hematology department is second to none. Of course I’m a little bias but your message was a validation for what I already feel about Mayo Clinic. A 2nd opinion there is definitely warranted for anyone who is questioning a diagnosis or treatment for blood cancers.
I hope your condition never progresses to AML but if it does and you require a SCT, you know where to go! ☺️
How often do you return for labs?

Hi Lori!

Given that I live about a 4 hour drive from Mayo, I'm still doing labs here in Chicago with Northwestern. There isn't much difference when it comes to labs that would make me want to return to Mayo just for labs.

As of now, we are doing labs 1x/week. As I start the next cycle of Inqovi, we might go to 2x/week - my platelets did drop down to 60 or so on the first cycle so we were close to needing an infusion but didn't pull the trigger on it - had recovered back to 70 on the next lab and went up from there.

Mayo is collaborating with my team at Northwestern so I feel comfortable still going to NW for the more routine stuff.

In about 3 months (or 2 or 3 cycles of Inqovi), we are going to repeat the bone marrow biopsy. I might go to Mayo for that but haven't decided yet. 4-5 hour drive home with a sore hip bone might suck. FWIW, Mayo read the same biopsy that Northwestern read and reported only 4% blasts (whereas NW was at 7%). It does make you wonder, eh?

I’m 58 and was diagnosed with AML DDX41 10 months ago. I have both germline and somatic DDX41 + CUX1 + CBL. Other than my bone marrow and blood readings, I’m in good health otherwise, no anaemia, no clear symptoms and indolent nature of my AML. I’m based in the UK and still have not started any treatment, but consider to start soon.

Would be interest to learn about other people’s experience with DDX41 and would be keen to talk to someone as well.

Whether my wait and watch approach makes sense or whether it is better to start the treatment asap?
What is a preferred approach - intensive treatment or reduced intensity? My doctor plans to start on Venetoclax+Azicitidine (rather than intensive chemo) - which makes sense to me, but good to understand other experiences/perspectives.
Whether to start HSCT asap after the chemo (as seems the medical/scientific consensus suggests)?
What is the risk of and experience with potential complications, including bacterial (gut bacteria), fungal and viral infections, refractory/relapse, acute or chronic GHVD, etc?
Any other practical recommendations, observations, etc.?

Welcome, @igorp You popped into the perfect conversation with some of our other members who have AML with the DDX41 mutation. There are other discussions as well that you might be interested in reading through. Please feel free to tag a member if you have questions. You can do that by clicking the blue reply oval in the reply so that the person gets notified.
Here is that list: https://connect.mayoclinic.org/search/

If you do require a HSCT, at least in my personal experience, having the transplant soon after the final round of chemo is usually advisable. Basically, the ‘cleaner’ we go into transplant the better chances for a longterm positive outcome. There are definitely considerations with a SCT. You mentioned several potential complications. There have been great advances in SCT protocol over the years to help mitigate the worst of the graft vs host issues. The first 3 months following the transplant is when the patient is most vulnerable so precautions are taken such as a ‘temporary’ immune system by taking prophylactic antibiotics, antiviral and anti-fungal meds, along with an anti-rejection medication for several months post transplant. It’s advisable to wear a mask and avoid situations where exposure to infection is high. I’m coming up on 7 years post transplant and frankly, I feel 98% back to my old self. (I’m 72).

Because the SCT is complex it’s important to have this done at a larger teaching/research hospital who does many of these procedures. Has your doctor brought up the conversation about requiring a transplant?

Hi Lori - yes, we have identified a potential unrelated donor with 10/10 match. My sister was a match too, but we had of course to search for an unrelated one given germline origin of my DDX41. The HSCT is going to be an important challenge with GVHD, chimerism, NRM, etc. My doctor told me that the most common reason for the latter (NRM) is our own (normally harmless) gut bacteria. Whether any known solution to this problem - other than generic prophylactic antibiotics?
At the current stage however, the most important decision for me is whether to start the chemo treatment (venetoclax + azacitidine) now or delay given no any symptoms and good overall physical condition. Despite substantially lower levels of WBC (especially neutrophils), I don’t seem to be more vulnerable to pathogens in practice than people around me. Since I was diagnosed 10 months ago, I continue my daily work in the office, taking busy public transportations, flying long and busy flights, doing shopping, socialising and even doing sport. My life is almost BAU - other than my regular hospital visits and abnormal blood readings. However, I know a number of things may go wrong once I start the treatment - and there is no way back. I do understand that the treatment is unavoidable in order to have a chance of remission and potential longer life, but the question is when?

Hi @igorp It sounds like you’re getting all your ducks in a row for a possible bone marrow transplant. Having an unrelated donor would be preferable in your case so it’s great that you have a match.

As for side effects post transplant, almost everyone has some gut related issues the first couple of weeks due to the preconditioning chemo. Many types of chemo interfere with rapidly dividing cells, which include cancer cells. Unfortunately there are other rapidly dividing cells in the body which become collateral damage such as the digestive system-from mouth down to the exit! The normal gut biome is also impacted so it can be a struggle.
One item that helped me immensely throughout my intensive AML treatments and the SCT was eating Greek yogurt daily with a teaspoon of ground flax mixed in. Also, during this time you may want to avoid dairy products which contain lactose. Lactose free products can help eliminate one source of inflammation. A caution though, no probiotic supplements!

It’s understandable to be concerned about all things related to the BMT (SCT) but if I may, try not to get too wrapped up in the potential side effects. Most of us who have undergone an allogenic transplant, will experience ‘something’ post transplant.

The main goal of the transplant IS to have some form of reaction to the new stem cells….gvhd. Think of it as graft vs leukemia. The newly implanted cells become your new immune system! Your old immune system no longer recognizes the leukemic cells. So the cancer cells can proliferate unchecked. The intention behind getting the new immune system is to recognize the cells as leukemic again. So if they reemerge after treatment, the new cells attack the cancerous cells and your life goes on…the cancer doesn’t. To do that you need to have some level of graft vs host event.

You have a big decision ahead on whether starting treatment or waiting. Those are good questions to work through with your doctor/bmt team. At 58, you’re still very young. If treatment can be delayed, they may suggest waiting until you actually need to go ahead with ‘the program’. It’s not unusual for people to have a BMT as late as their early 70s. If you can avoid it until later, that may be an attractive option.

It’s really difficult to make this decision when you’re feeling healthy and energetic. What’s your gut feeling?