EBMT 2025 | Clinical outcomes of MRD based on GvHD prophylaxis in patients with ALL or AML undergoing alloSCT

There have been multiple data coming from mainly retrospective cohorts that have shown that MRD positivity remains a significant factor in terms of long-term survival outcomes for patients undergoing allogeneic transplantation. There are some retrospective data that suggest that myeloablative conditioning and haploidentical transplantation based on the fludarabine melphalan conditioning could sometimes or could possibly overcome this negative outcome of MRD positivity. There’s limited data in the post-transplant cyclophosphamide era with in general allogeneic and particularly since the results published on PROGRESS III, most US institutions have switched into post-transplant cyclophosphamide being their main GVHD prophylaxis regimen, particularly in patients with reduced intensity conditioning. 

So we decided to review our own experience at our center. We had 97 patients with acute leukemia that had MRD data prior to transplantation. This included approximately half and half of patients with acute myeloid leukemia and acute lymphoblastic leukemia, and decided to review their general outcome based on both MRD positivity and GVHD prophylaxis status. 

And so in this cohort overall both the CNI methotrexate-based group and the post-transplant cyclophosphamide-based groups were overall well balanced. We did see as expected an increase in haploidentical transplantations amongst patients with PTCy, but other than that the only small detail that was noted was that our patients with post-transplant cyclophosphamide did have an increased rate of NRAS mutations. 

And so taking a look into their overall outcomes, we saw that patients with MRD-positive disease had a significantly increased incidence of relapse at two years of approximately 59% as compared to a little bit less than 20% amongst patients that were MRD-negative. Then that of course translated into worsened outcomes both from a relapse-free survival perspective, a graft-versus-host disease-free relapse-free survival, and overall survival. This was persistent amongst MRD positivity regardless of CNI or PTCy group throughout all of these outcomes. 

And so in general we are seeing that even though there are some suggestions in some literature that we are, of course, on the right track, there’s still a lot that needs to be done as MRD positivity remains a significant factor for decreased or inferior outcomes long term.

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