Transplantation Outcomes of 8/8-Matched Unrelated Donors Compared with Matched Siblings and Autologous Transplantation for Acute Myeloid Leukemia with Intermediate Cytogenetics in First Remission

There have been a few multicenter or registry data assessing the feasibility of unrelated donors (URD) in acute myeloid leukemia (AML) compared to HLA-matched sibling donors (MSD). These studies suggest that MSD and HLA-matched URD have comparable outcomes. However, the small number of patients in first complete remission (CR1) and the lack of high-resolution HLA typing in these studies make it difficult to clearly determine the role of 8/8-matched URD in patients with AML CR1. Furthermore, using 8/8-matched URD is not currently standard practice in patients with AML CR1 having intermediate cytogenetics, particularly those without poor risk features, when MSD are not available. These patients are also candidates for non-allogeneic stem cell transplantation (allo-SCT) therapy, such as autologous peripheral blood stem cell transplantation (auto-PBSCT). In order to clarify the role of 8/8-mateched URD in these patients, transplantation outcomes should be compared with non-allo-SCT therapy as well as MSD.

Between 2002 and 2009, 567 adult patients with AML underwent transplantation from MSD, URD, and autologous sources. According to the risk-adapted treatment strategy, AML CR1 with intermediate cytogenetics received allo-SCT as a post-remission treatment, if MSD or 8/8-matched URD was available. Patients with no available donor received autologous transplantation. To determine the role of 8/8-matched URD on transplantation outcomes in patients with intermediate cytogenetics, we evaluated 288 patients with intermediate cytogenetics who underwent transplantation from autologous sources (n=89) or allogeneic donors (n=199) consisting of 8/8-matched URD (n=54) and MSD (n=145) at CR1.

In multivariate analyses, 8/8-matched URD had comparable 6-year overall survival (OS, P=0.997), disease-free survival (DFS, P=0.951), and relapse (P=0.672) to MSD, whereas 8/8-matched URD had a higher OS (P=0.070) and DFS (P=0.035) with lower relapse (P=0.009) than autologous transplantation. No difference in non-relapse mortality was observed according to donor type. Notably, these equivalent or superior outcomes of 8/8-matched URD compared with MSD or autologous transplantation, respectively, were particularly evident in patients without poor risk features (n=200), such as older age, hyperleukocytosis at diagnosis, and myelodysplasia-related changes, who are not usual candidates for URD transplantation.

In conclusion, this study confirmed the comparable outcomes of 8/8-matched URD with MSD in AML CR1 with intermediate cytogenetics. Additionally, this study strongly suggests that 8/8-matched URD is preferable to auto-PBSCT in AML CR1 with intermediate cytogenetics, when MSD are not available. Finally, our data indicate that 8/8-matched URD are feasible next option in AML CR1 with intermediate cytogenetics, when lacking MSD, even in patients without poor risk features.