ASH 2022 | AlloSCT outcomes from younger matched unrelated donor versus older sibling donor for AML

Allogeneic transplantation offers cure for patients with AML, particularly, those who carry a high-risk disease. Now, while we have decade long analyses showing that we have done pretty well over the last few decades and years with decreasing non-relapse mortality, GvHD and infections, relapse has gone up. So, biologically, relapse reduction is a critical unmet need in the transplant setting.

All prior studies that have been conducted, either predated the contemporary transplant practice, or were single-centered or underpowered. With this in mind, we wanted to conduct this study. We hypothesized that allogeneic transplantation, when performed for older adults with AML, with a younger matched unrelated donor as compared to older matched sibling donor, confers superior outcomes. In terms of method, we used CIBMTR database, we had strict inclusion, exclusion criteria. We defined older matched sibling donor as a donor who was either 50 years of age or older and younger matched unrelated donor who was either 35 or younger.

Now, results wise, we obviously included standard GvHD prophylaxis regimens, excluding post-transplant cyclophosphamide, or any other combination of PTCY-based GvHD prophylaxis regimens. The results showed that out of more than 46, 4700 patients, there were significant relapse reduction with younger MUDs, as compared to older MSDs. That did come at a cost of slightly higher non-relapse mortality with younger MUDs, as compared to older MSDs, in the earlier years, from 2011 through 2015. But in the more recent years from 2016 through 2018, that NRM disadvantage vanished. In a multivariate analysis, five-year adjusted cumulative incidence of relapse was also lower with younger matched unrelated donors as compared to older matched sibling donors. Really in the earlier years again, the 5-year cumulative incidence of non-relapse mortality was higher with younger MUDs. That disadvantage vanished in the recent years, at 5 years.

In multivariate analysis, while there was no impact on overall survival, there was a signal in disease-free survival. Particularly, there was a 5-year adjusted DFS, disease leukemia free survival benefit with younger MUDs as compared to older MSDs, in patients with acute myeloid leukemia. Based on these registry-based analysis results, our group concludes that moving forward, when we have both donor types available for patients, younger match unrelated donor should be the preferred donor for transplant centers and practitioners. And the way curves [inaudible] each other at 6 months mark, relapse curves and disease survival curves, really signal that it’s not an impact of conditioning related effect. It’s rather a GvL effect, graft-versus-leukemia effect, which is driven by donor immune repertoire, decreased clonal hematopoieses of indeterminate potential, and really an impact which is driven by donor. Hence, we do think this is a hypothesis generating a potentially practice training study.