STAG2 mutation predicts superior posttransplant survival in acute myeloid leukemia treated with low-intensity induction

Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly offered to patients with acute myeloid leukemia (AML) who achieve remission on low-intensity, venetoclax-based induction, but the molecular determinants of posttransplant outcome in this population are poorly defined. [ 1 ] In a recent report of 111 patients with newly diagnosed AML who received frontline venetoclax plus a hypomethylating agent (Ven-HMA) and subsequently underwent allogeneic HSCT, age ≥ 65 years, STAG2 mutation ( STAG2 MUT ) and DNMT3A mutation ( DNMT3A MUT ) were each associated with superior posttransplant overall survival (OS). [ 2 ] Combined into a three-tier score, these variables separated 3-year OS of 89%, 59%, and 19%. Two of the three components — older age and DNMT3A MUT — invert conventional prognostic expectations, and the third, STAG2 MUT , is derived from a subgroup of 12 patients. Given the counterintuitive prognostic associations of older age and DNMT3A MUT , we therefore applied the model to an independent Asian cohort transplanted after low-intensity induction for external validation.