Azacitidine maintenance therapy post-allogeneic stem cell transplantation in poor-risk acute myeloid leukemia.

Abstract

OBJECTIVE/BACKGROUND\nAllogeneic hematopoietic stem cell transplant (HSCT) is the potential curative modality for poor-risk acute myeloid leukemia (AML), relapse remains the main reason for transplant failure. Early-phase studies showed azacitidine is safe for post-transplant maintenance therapy in AML.\n\n\nMETHODS\nWe performed a single institutional prospective cohort study to evaluate the benefit of azacitidine maintenance therapy following allogeneic HSCT in poor-risk AML. The main objective of this study is to generate a hypothesis aiming to optimize post-transplantation outcomes in poor-risk AML. Forty-nine adults with poor-risk AML who underwent allogeneic HSCT were evaluated in a nonrandomized prospective cohort fashion. Thirty-one participants received post-transplant azacitidine (32\u202fmg/m2) on Days 1-5 for a 28-day treatment cycle beginning approximately 40\u202fdays after transplantation. The study was controlled using 18 matched individuals who were on a noninterventional surveillance protocol.\n\n\nRESULTS\nThe relapse rate was significantly higher in the control cohort (66.67%) versus (25.81%) in the azacitidine maintenance cohort (p\u202f<\u202f.005). Time to relapse was significantly prolonged by azacitidine maintenance, not reached versus 4.1\u202fmonths in the control arm (p\u202f<\u202f.0001). In addition, median overall survival was lower in the control cohort at 7.6 versus 27.4\u202fmonths in the interventional cohort (p\u202f<\u202f.0001). At a median follow-up of 24\u202fmonths, incidence of graft-versus-host disease (GVHD) did not differ between study groups (p\u202f=\u202f.325). In both cohorts, minimal residual disease was correlated with higher hazard of relapse (95% confidence interval, 2.31-13.74; p\u202f<\u202f.001).\n\n\nCONCLUSION\nWe conclude that low dose azacitidine maintenance following allogeneic HSCT in poor-risk AML, decreased relapse rate, and increased both the time to relapse and overall survival without increased risk of GVHD.