Hematopoietic stem-cell transplantation (HSCT) has evolved from a salvage procedure for otherwise-fatal leukemia into a curative modality spanning nearly every hematological malignancy and several non-malignant disorders. The contemporary landscape has been reshaped by three converging forces: the refinement of disease-specific risk stratification (European LeukemiaNet [ELN] 2022 for acute myeloid leukemia, Molecular International Prognostic Scoring System [IPSS-M] for myelodysplastic syndromes, Mutation-Enhanced International Prognostic Scoring System [MIPSS70+ v2.0], and Myelofibrosis Transplant Scoring System [MTSS] for myelofibrosis); the integration of measurable residual disease (MRD) into dynamic, response-adapted transplant decisions; and the approval of immune effector cell therapies that have displaced transplantation from several long-standing indications while creating new ones (bridge-to-transplant, post-CAR-T consolidation). In parallel, post-transplant cyclophosphamide (PTCy) has largely equalized outcomes across matched sibling, matched unrelated, and mismatched alternative donors, and novel agents (ruxolitinib, belumosudil, axatilimab) have materially reduced graft-versus-host disease (GVHD) morbidity. This narrative review synthesizes current indications for autologous (auto-HSCT) and allogeneic (allo-HSCT) transplantations in adults, and flags areas of persistent controversy where randomized data are still maturing. Across all indications, the clinician’s question is shifting from “transplant or not?” towards “which donor, which conditioning, which bridge, and which post-transplant maintenance?”, each tailored to disease biology, MRD trajectory, and patient fitness.

Allogeneic hematopoietic stem cell transplantation represents the only potentially curative therapeutic approach for Acute Myeloid Leukemia. The choice to perform an allogeneic hematopoietic transplant is the result of a decision-making process that considers disease-related factors (AML-risk category and the state of disease at the time of transplant), the type of donor available and his characteristics (HLA compatibility, gender, CMV serostatus) and the individual risk associated with the procedure itself. The choice of the appropriate conditioning regimen depends on the patient’s age and comorbidities. While the introduction of reduced intensity regimen and the availability of alternative donors allows more patients to be eligible for transplantation, myeloablative conditioning remains the standard of care for fit patients. Disease relapse is the leading cause of treatment failure and new strategies attempting at reducing the relapse incidence post transplantation are currently being investigated.