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EBMT 2025 | Preventing GvHD in sibling and unrelated transplants in AML: ATG versus PTCy
Arnon Nagler, MD, Chaim Sheba Medical Center, Tel-Aviv, Israel, discusses the main strategies for preventing graft-versus-host disease (GvHD) following allogeneic stem cell transplant (alloSCT) for patients with acute myeloid leukemia (AML), emphasizing the importance of preventing this complication. Prof. Nagler highlights many approaches, drawing focus on the use of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy), explaining when to use each approach. This interview took place at the 51st Annual Meeting of the EBMT in Florence, Italy.
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Transcript
So, GVHD is the main obstacle for successful allogeneic transplant and the main cause of mortality and so we need to prevent GVHD. And so besides the calcineurin inhibitor in combination with methotrexate and MMF, the two main strategies are ATG and PTCy. ATG, we have 30-40 years of experience, six randomized studies. In all of them, there is a decrease in acute and chronic GVHD, but there is no decrease in non-relapse mortality and no improvement in overall survival...
So, GVHD is the main obstacle for successful allogeneic transplant and the main cause of mortality and so we need to prevent GVHD. And so besides the calcineurin inhibitor in combination with methotrexate and MMF, the two main strategies are ATG and PTCy. ATG, we have 30-40 years of experience, six randomized studies. In all of them, there is a decrease in acute and chronic GVHD, but there is no decrease in non-relapse mortality and no improvement in overall survival. And PTCy, which has been pioneered in Haplo, showed reduction in non-relapse mortality and acute GVHD, and in the American CTN 1703, in which they compared the PTCy-based to the conventional methotrexate tacrolimus, they showed reduction in severe acute GVHD, chronic GVHD, and improvement in GRFS. And this is in unrelated, matched unrelated, and sibling transplant. So PTCy is moving to the unrelated setting, which is the main problem we have there with GVHD. And these two strategies are available.
EBMT recommendations don’t recommend PTCy in sibling transplantation, and for matched unrelated and mismatched unrelated, it’s recommended either PTCy or ATG. And the newer data, mainly from registry-based studies, we don’t have a randomized study, all of them showing, or most of them will show, at least in the mismatched unrelated and some in the matched unrelated, an advantage of PTCy as for acute GVHD and non-relapse mortality. And it’s less so in siblings. So I would say that the more there is HLA disparity, you have more place for PTCy over ATG, and we need a randomized study. The other, the future direction, is combining the two in order that we can reduce the doses of ATG and PTCy and have less toxicity. Also we may have more efficacy and because the dose and the timing is not decided for ATG but also for PTCy we are reducing the doses in order not to have cardiac toxicity or hemorrhagic cystitis. And we need to make the endpoint of the patient quality of life and to see that we are not increasing infection and relapse rate. Currently with the combination of PTCy to ATG there is a decrease in acute GVHD in some of the studies without increase in relapse or infection.
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