EBMT 2026 | Promising approaches for optimizing transplant conditioning in AML

Transplant conditioning is a very important part of the transplantation and also for the treatment strategy for AML. And we cannot change the age of the patient, we cannot change the type of the disease, but we can modify the conditioning, and this is something that we should optimize in order to have a successful transplant. Now, for 25 years, we were debating about the intensity of the conditioning, myeloablative, and reduced intensity. And after 25 years, the overall survival and leukemia-free survival were the same, but with less intense conditioning, we have less organ toxicity, less transplant-related mortality, and so we can offer transplant to actually any age. And the median age of AML and MDS is 72, so it’s very important that we can give transplantation with slight conditioning so we can offer transplant to any age. 

I think that in the current era, we should move from cytotoxic-based chemotherapy to more intelligent conditioning based on immunological means or immunological aspects. So introducing new agents and new drugs to the conditioning and maybe the platform for immunotherapy post-transplantation. We can also give the chemotherapy in accordance with the PK studies. There are some data that you can start the chemotherapy busulfan day minus 22 before the transplant or melphalan at day minus 11 before the historical conditioning in order to make it less toxic. But, you know, introducing new drugs like venetoclax, decitabine, azacitidine (vidaza), cladribine, these are drugs that are extremely important, they also manipulate in part the immune system like NK cells, and they are being introduced now into conditioning in order to optimize conditioning, especially for patients that are elderly. So there we have the issue of toxicity. And for relapsed/refractory AML, and there we need to have a really optimal conditioning to conquer the disease. And we can give post-transplantation, you know, another time, or also introduce targeted therapy. 

Now, the conditioning may be based in the future on mutation profile on cytogenetics and MRD. We have some data from the EBMT that shows that there was no difference between the patients that received reduced intensity or myeloablative, or now we do it according to the TCI. But patients that were intermediate risk cytogenetic and FLT3-positive benefit from more intense conditioning, while patients that were FLT3-negative benefit from less intensive conditioning. And there is this data, all data from the CIBMTR, CTN, that intense conditioning helps for a high-risk mutation, and not everybody agrees with this. The Figaro study did not show this data. So we may base the conditioning also, optimize the conditioning according to the mutation, and also include the targeted drug. 

And I will say that there is a new horizon for the conditioning. We are back to graft manipulation. There is the phase three ORCA study in which they engineered the graft with T-regulatory cells with beautiful results. There is radio-labeled antibodies. There is targeted TBI. And also there is data from China about CAR T-cells paving the way for the transplantation with no need for conditioning. So maybe, you know, not in our time, but we will talk about chemotherapy-free conditioning or immune-based conditioning.

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