Allogeneic Transplantation in Acute Myeloid Leukemia in the Era of Novel Therapies: Changing Indications and Dynamic Risk Assessment

Allogeneic HSCT remains a major potentially curative treatment for patients with AML at high risk of relapse. However, the rapid development of targeted agents and novel non-intensive therapies has substantially changed the therapeutic landscape, raising questions regarding the optimal timing and indications for transplantation. In this narrative review, we discuss how recently introduced therapeutic strategies may influence transplant decision-making, with particular emphasis on disease risk, treatment response, measurable residual disease, and the integration of pharmacological therapy before and after allogeneic HSCT. Novel therapies have primarily modified rather than replaced the role of allogeneic HSCT. Venetoclax-based regimens may allow initially unfit patients to achieve remission and become transplant candidates. At the same time, targeted agents such as FLT3, IDH, and Menin inhibitors can provide effective disease control in molecularly defined AML, particularly in the relapsed/refractory setting. They may enable transplantation in patients with limited therapeutic options. Growing evidence also supports using selected targeted agents after allo-HSCT, particularly FLT3 inhibitors, while post-transplant maintenance with IDH or Menin inhibitors and hypomethylating agents remains investigational. Across these settings, MRD is emerging as an increasingly important tool for refining transplant decisions and identifying patients who may benefit from additional therapy. The role of allogeneic HSCT in AML is evolving from a decision based predominantly on baseline genetic risk toward a dynamic, response- and MRD-adapted strategy. Novel agents should not currently be viewed as alternatives to transplantation in patients with a substantial risk of relapse, but rather as complementary therapies that may improve disease control before HSCT and reduce relapse risk afterward. Prospective studies integrating targeted therapy, MRD assessment, and post-transplant maintenance are needed to define the optimal therapeutic sequence and identify patients who may safely avoid transplantation.