BACKGROUND Relapsed and refractory (R/R) acute myeloid leukemia (AML) represents a significant therapeutic challenge, with limited treatment options and poor survival outcomes. While salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative strategy with potential efficacy for these patients, its application in patients who fail to achieve complete remission (CR) before transplantation remains controversial due to historically poor survival rates. To date, there is no consensus on how to optimize transplantation strategies for this high-risk cohort, necessitating urgent real-world evidence to guide clinical practice.

OBJECTIVES This study seeks to evaluate the feasibility, efficacy, and prognostic factors associated with salvage allo-HSCT in R/R AML patients in non-CR status, providing valuable insights into its role as a potential therapeutic strategy when other options are exhausted.

METHODS This retrospective study analyzed 120 R/R AML patients who underwent allo-HSCT in non-CR status at Seoul National University Hospital between 2005 and 2024. Overall survival (OS) was estimated using the Kaplan-Meier method, while relapse and nonrelapse mortality (NRM) were assessed within a competing-risks framework. Prognostic factors were analyzed using univariate and multivariate Cox regression models.

RESULTS The median OS was 5.2 months, with a 3-year OS probability of 23%. At three years, the cumulative incidence of relapse was 45.7%, while NRM reached 51.1%. In multivariable analysis, several variables retained independent associations with poorer survival, including age ≥ 50 years (HR 2.90, 95% CI 1.59-5.29; P = 0.001), adverse cytogenetics (HR 2.39, 95% CI 1.46-3.91; P = 0.001), and a bone marrow blast count ≥ 20% at the time of transplantation (HR 1.86, 95% CI 1.15-3.02; P = 0.012). Among post-transplant complications, severe acute graft-versus host disease (GVHD) was associated with markedly inferior survival, whereas chronic GVHD did not significantly affect OS.

CONCLUSIONS Salvage allo-HSCT in non-CR shows substantial variability in outcomes, highlighting the importance of careful patient and donor selection, particularly regarding age, cytogenetic risk, disease burden, and donor type. Severe acute GVHD was clearly associated with markedly worse survival. These findings highlight the need for individualized donor choice and early control of acute GVHD to improve outcomes in this high-risk group.