Abstract
Acute myeloid leukemia (AML) is a heterogeneous malignant disorder of myeloid precursor cells, with high relapse rates, particularly in patients who fail to achieve morphological remission after induction therapy. Allogeneic hematopoietic cell transplantation (allo-HCT) can induce durable remissions through the graft-versus-leukemia (GVL) effect, yet current approaches of allo-HSCT often fail, with relapse rates of ∼40% within 6 months post-transplant. Outcomes following allo-HCT are inversely proportional to leukemia burden at the time of transplant. Both morphological relapse (≥5% blasts in the marrow) or minimal residual disease (MRD) positivity predict significantly reduced overall survival rates. Emerging strategies to improve outcomes in patients with high leukemic burden include aggressive bridging therapies (encompassing intensive salvage chemotherapy, hypomethylating agents, targeted inhibitors, and sequential induction-conditioning approaches such as FLAMSA), tailored conditioning regimens, post-transplant maintenance therapy, and innovative graft engineering methods. Graft engineering strategies, such as ORCA-T, which engineers stem cell grafts with a defined ratio of T-regulatory cells to effector T cells, are particularly promising and under evaluation in phase III clinical trials. These approaches aim to improve upon the poor outcomes for patients with persistent/relapsed AML undergoing allo-HCT.