EHA 2026 | Considerations when screening donors for CH mutations to assess the risk of donor-derived leukemia

Not all mutations have the same level of risk for the patients, for instance. DDX41, for instance, it’s the largest mutation, but it’s less risky than the other mutations, of course. So the idea is, do we need to be worried about every single mutation? I don’t know. So we gave in the article, we published recently, you know, some recommendations regarding the mutations one by one. At least the mutations we are aware of right now. So maybe this list can be enlarged. We need to be careful regarding this. But this brings me to the question. So do we need to screen all donors before transplantations? My simple question is no. Otherwise, it’s not possible. The majority of our patients are receiving transplants from unrelated donors. Now, we will not start screening everybody. And to be honest, if you look at the risk of donor-derived leukemia after transplantation, it’s a small proportion of the patients. So we need to do this balanced benefit-risk for the patients. Now, do we need really, when we observe this genetic mutation in a recipient, to screen all the family of the patient to select a donor or to decide right away to go for unrelated donor transplantation. The question is more difficult. I would say we need to take into account the psychological impact of such, you know, you have one member of your family with leukemia. This is very bad news, catastrophic for the family. And then you will go to the family and say, hey, guys, we need also to check if you have this mutation, et cetera. So the psychological impact on the family, we need to save the patient, but we can kill the whole family, you know, psychologically speaking, you know, because this is something very worrying. I would say so we need really to think when we decide to do this to do it carefully with caution, because not because you are harboring this mutation will you develop 100% leukemia. So why put you in this psychological state, saying you have this, you will develop, you know, when we are not sure that 100 percent you will develop the leukemia? It’s, I don’t know if really we need to alert you about something like this. We need really nowadays, we have a lot of means in our hands, and we can discover a lot of things, but I’m not sure that is the right way, you know, to do it. We need to think about this, not because I discovered something, I need to announce this to the whole family. So we need to be careful with this. And the last thing I can say, yes, I can go to the family, I can announce, I can go screening if I have something to do, if I can give them a treatment to prevent the development of leukemia. But if I have nothing but announcing the bad news, so we need to really take this into account. You know, when we are a doctor or researcher, we are within our discoveries and these mutations, et cetera, we don’t take into account the psychological aspect of the whole family. This should be one of our roles, actually, to protect people from these bad news. For these bad news, we have nothing to do, and we don’t see the real impact of this discovery.

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