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EBMT 2025 | Optimizing conditioning regimens for SCT in AML and MDS
Mohamad Mohty, MD, PhD, Saint-Antoine Hospital, Paris, France, comments on the optimization of conditioning regimens for stem cell transplantation (SCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), highlighting that despite recent advancements, there is no definitive answer regarding the best choice of regimen. Prof. Mohty notes that new approaches, such as the use of treosulfan and targeted antibodies, are being explored, but emphasizes that the priority should remain on minimizing toxicity. This interview took place at the 51st Annual Meeting of the EBMT in Florence, Italy.
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Transcript
The choice of a conditioning regimen or a preparative regimen prior to allogeneic stem cell transplantation is a crucial step for the success of the transplant procedure. In the last few years, we thought that this is a case closed. First, may I kindly remind you that historically, we lived with two famous myeloablative conditioning regimens, namely cyclophosphamide, high-dose TBR, or busulfan, high-dose busulfan, and high-dose cyclophosphamide, standard conventional myeloablative conditioning regimens...
The choice of a conditioning regimen or a preparative regimen prior to allogeneic stem cell transplantation is a crucial step for the success of the transplant procedure. In the last few years, we thought that this is a case closed. First, may I kindly remind you that historically, we lived with two famous myeloablative conditioning regimens, namely cyclophosphamide, high-dose TBR, or busulfan, high-dose busulfan, and high-dose cyclophosphamide, standard conventional myeloablative conditioning regimens.
In the late 90s, early 2000, we’ve seen the advent of the so-called reduced-intensity conditioning regimens or non-myeloablative regimens. And this has been a huge and significant turning point in the practice of allotransplant because it allowed to offer a curative treatment option like allotransplant to the older and frail population who are in need. And we had, in the last 20 years a very nice development and refinement of the use of these reduced intensity conditioning regimens.
Obviously there is no ideal regimen, different institutions, different countries have some preference for this or this regimen. Fludarabine is a key component of all of these regimens and you may wish to combine it with busulfan. Flu-bu is one of the most popular regimens in Europe. Some colleagues are very keen on Flu-Mel, Flu-melphalan, but recently we’ve seen an increased enthusiasm about the use of fludarabine and treosulfan. And this is based on this Phase III randomized trial published in 2020, comparing flu-bu to flu-treo, showing superiority of flu-treosulfan.
So you can see the case is not closed. And despite many years of development, we can see some new approaches, and I think treosulfan is definitely a new player in this arena. There are also some targeted antibodies that are being developed. So you can see, I think we will continue to work on the development of conditioning regimens.
But at the end of the day, I would say irrespective of whatever conditioning you prefer or you would like to use, we should not forget about the priority, and this is about reducing the toxicity. And this is where it is quite difficult in this landscape, because we would like to find this delicate balance between reducing the toxicity, reducing the cytotoxic component of the regimen, while improving or favoring disease control as part of the conditioning regimen, but also trying to promote the graft versus tumor or graft versus leukemia effect. So I think we will continue to improve, but there are already some great achievements in this space.
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