Does anyone else have AML with ddx41 genetic mutation?

Hi @rosejen - indeed, DDX41 is not the most common mutation, but there is a sizable body of research in recent years. Mayo clinic is one of them. Their observations and conclusions on DDX41 slightly stand out as unorthodox compared to recommendations by some other leukaemia clinics, but I think they make a good point.

There are 2 big questions with the treatment - when to start the chemo and whether or not to
do allo HSCT immediately after that:

1. Normally with AML, there is no questions when to start. The answer to this question is in its name - Acute Leukaemia. Things usually unravel very quickly. This is not the case with germline DDX41 as a founding mutation. This MDS/AML subtype usually takes years to progress and has a very indolent nature. Your mum however is in the AML stage by now and this is where a general recommendation my AML profession is to start the treatment. I however, have not started myself yet (after 12+ months after the diagnosis), but may start soon. Age and health condition is another important factor.

2. If you don’t do HSCT after the chemo, then relapse is almost guaranteed within 3 years. You can find an article on DDX41 published by N. Duployez in 2022 (if not mistaken). This was quite fundamental paper on this mutation at the time and, among other things, illustrated the high risk of relapse from DDX41 AML if no transplant. The latter is the only cure for germline DDX41 known at this stage. On a flip side, HSCT is a serious risk and many things can go wrong (risk of rejection, GVHD and other NRM from pathogens). Risk from gut bacteria and sepsis are very important contributors to NRM. So, this is an important risk trade off. In my case however, I have no plans to delay the transplant once I start the treatment (and assuming CR - which is not guaranteed). Your mum’s case is not exactly the same, so such decision needs to be carefully evaluated based on all factors - most importantly, her current health condition.

DDX41 also tends to have a better % of CR with Ven + Aza compared to average AML cases. So, your consultant is correct about more favourable outlook, but it also has some darker sides too (risk of relapse and NRM risks after the chemo).

In which hospital do you plan the treatment? Which mutation where identified by molecular analysis/NGS, their VAFs, % of blasts, FBC and Haemoglobin readings?

We can also connect offline if you share your email address.