Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT

Abstract

Background: Optimal post-remission strategy for patients with acute myeloid leukemia (AML) is matter of intense debate. Recent reports have shown stronger anti-leukemic activity but similar survival for allogeneic stem cell transplantation (allo-HSCT) from matched sibling donor compared to autologous transplantation (auto-HSCT); however, there is scarcity of literature confronting auto-HSCT with allo-HSCT from unrelated donor (UD-HSCT), especially mismatched UD-HSCT.

Methods: We retrospectively compared outcome of allogeneic transplantation from matched (10/10 UD-HSCT) or mismatched at a single HLA-locus unrelated donor (9/10 UD-HSCT) to autologous transplantation in patients with AML in first complete remission (CR1). A total of 2879 patients were included; 1202 patients received auto-HSCT, 1302 10/10 UD-HSCT, and 375 9/10 UD-HSCT. A propensity score-weighted analysis was conducted to control for disease risk imbalances between the groups.

Results: Matched 10/10 UD-HSCT was associated with the best leukemia-free survival (10/10 UD-HSCT vs auto-HSCT: HR 0.7, p = 0.0016). Leukemia-free survival was not statistically different between auto-HSCT and 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 0.8, p = 0.2). Overall survival was similar across the groups (10/10 UD-HSCT vs auto-HSCT: HR 0.98, p = 0.84; 9/10 UD-HSCT vs auto-HSCT: HR 1.1, p = 0.49). Notably, in intermediate-risk patients, OS was significantly worse for 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 1.6, p = 0.049), while it did not differ between auto-HSCT and 10/10 UD-HSCT (HR 0.95, p = 0.88). In favorable risk patients, auto-HSCT resulted in 3-year LFS and OS rates of 59 and 78 %, respectively.

Conclusions: Our findings suggest that in AML patients in CR1 lacking an HLA-matched sibling donor, 10/10 UD-HSCT significantly improves LFS, but this advantage does not translate in better OS compared to auto-HSCT. In intermediate-risk patients lacking a fully HLA-matched donor, auto-HSCT should be considered as a valid option, as better survival appears to be provided by auto-HSCT compared to mismatched UD-HSCT. Finally, auto-HSCT provided an encouraging outcome in patients with favorable risk AML.

Keywords: Acute myeloid leukemia (AML); Allogeneic transplantation; Autologous transplantation; Matched (10/10) and mismatched (9/10) unrelated donor transplantation; Post-remission therapy.

Fig. 1

Outcome by type of transplant in the global population. The cumulative incidence of non-relapse mortality (a) and relapse (b) by transplant type; the probability of leukemia-free survival (c) and overall survival (d) in the global population. Kaplan-Meier curves and Cox analysis are weighted for propensity score; Cox analysis is further adjusted for kind of conditioning and stem cell source

Fig. 2

Leukemia-free survival and overall survival by type of transplant in good-risk patients. The probability of leukemia-free survival (a) and overall survival (b) in good-risk patients

Fig. 3

Leukemia-free survival and overall survival by type of transplant in intermediate-risk patients. The probability of leukemia-free survival (a) and overall survival (b) in intermediate-risk patients

Fig. 4

Leukemia-free survival and overall survival by type of transplant in poor-risk patients. The probability of leukemia-free survival (a) and overall survival (b) in poor-risk patients