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ASH 2025 | AlloSCT in older, fit patients with AML: understanding predictors of post-transplant toxicity

Charles Craddock, CBE, FRCP(UK), FRCPath, DPhil, FMedSci, University of Birmingham, Birmingham, UK, discusses the increasing importance of allogeneic stem cell transplantation (alloSCT) as a curative modality in older, fit patients with acute myeloid leukemia (AML). Prof. Craddock emphasizes that age is no longer the primary consideration for alloSCT and that the unmet need is to understand the predictors of post-transplant toxicity. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.

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Transcript

I think one of the themes of this meeting is the increasing importance of allogeneic stem cell transplantation as a curative modality in older, fit patients with acute myeloid leukemia. We have seen data presented which have shown increasing donor availability, the opportunity using post-transplant cyclophosphamide to use mismatched unrelated donors, getting almost equivalent results to what you see with matched unrelated donors...

I think one of the themes of this meeting is the increasing importance of allogeneic stem cell transplantation as a curative modality in older, fit patients with acute myeloid leukemia. We have seen data presented which have shown increasing donor availability, the opportunity using post-transplant cyclophosphamide to use mismatched unrelated donors, getting almost equivalent results to what you see with matched unrelated donors. And also, strikingly, randomized studies showing two-year transplant-related mortality now in the region of 5% to 10%, much lower than was reported say 10 or 15 years ago. But the centrally important question given the curative potential of an allograft is which older patient is fit. What is clear is that age is no longer the prime consideration and certainly in the UK we are happily transplanting fit adults up to the age of 75 and my American colleagues can even extend it to 80. The assessment that we conventionally use is something called the HCT-CI and this is to some degree an imperfect tool. My assessment is that the best guide is a consultation with the patient before starting a real transplant conversation, which looks at how fit the patient was before they were diagnosed with AML. And I think people who have good exercise tolerance are active and have modest or minimal comorbidities. The evidence now is accumulating that even up to the age of 75, they have an acceptable transplant-related mortality. I think the area of unmet need is to understand what are the predictors of toxicity post-transplant, particularly related to the treatment of graft-versus-host disease with steroids. This is the major complication of an allograft now in older patients, is intolerance of steroids. And so I think there’s quite a lot of work to be done in trying to predict exactly which patients, if they got GvHD, would tolerate steroids poorly.

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