ESH AL 2018 | Improving outcomes after transplant in AML

Charles Craddock

Charles Craddock, CBE, FRCP (UK), FRCPath, DPhil, of the University of Birmingham, Birmingham, UK, discusses how we can improve outcomes after transplant in acute myeloid leukemia (AML). Prof. Craddock touches upon a range of avenues, including measurable residual disease, the optimal conditioning regimen and novel therapies. This video was recorded at the 2018 European School of Hematology (ESH) Clinical Updates on Acute Leukemias, held in Budapest, Hungary.

Transcript (edited for clarity):

One of the central themes of this meeting has been the increasingly central role of allogeneic transplantation in optimizing outcomes in adults with AML, and the recognition that there’s now almost universal donor availability and that for patients with a predicted risk of relapse if treated with conventional chemotherapy of more than 40-45%, an allograft should be considered if they’re fit. So, that means almost every patient over 60, unless they’ve got good risk cytogenetics, is now an allograft candidate providing their fit. So, we have to address now how we improve outcomes after transplant.

There’s been a substantial reduction in transplant-related mortality in the last 20 years; a lot of that due to improved supportive care, but also reductions in the incidence of severe acute graft-versus-host disease. Disease relapse, however, remains the major problem and occurs in up to 60% of patients allografted for an adverse karyotype or otherwise defined high-risk AML, that’s a definition that includes not only adverse karyotype, the presence of a FLT3 ITD mutation at diagnosis, failure to achieve a CR after one course of induction chemotherapy and, increasingly now, molecular definitions of adverse risk, including mutations in p53.

So, if one thinks about what we could do to reduce the risk of relapse, it’s important to note that the emerging retrospective data says that the MRD status going into transplants is an important predictor of relapse, although there is, as yet, no prospective data around this. But if it’s the case that the presence of residual disease is an important predictor, then one wants to ask a question, and it was raised a number of times at this meeting, as to whether there’s anything you could do to reduce the level of MRD and actually whether that reduction impacts on relapse risk. So, randomized trials are required in that area using either novel agents or drugs such as CPX-351.

The next question is what’s the optimal conditioning measurement, particularly in older patients over the age of 50, and there’s a number of possibilities that are emerging as new conditioning regimens, which appear to be associated with the reduced risk of relapse, but prospective trials of the TBF regimen that has been pioneered by Bacigalupo with thiotepa and the FLAMSA regimen that’s been pioneered by Christoph Schmidt are very important.

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