Acute Myeloid Leukemia (AML) and related cancers of the blood system can be cured by hematopoietic stem cell transplantation from healthy allogeneic donors (allo-HSCT), due to the capacity of immune cells from the donor to recognize and attack mismatched human leukocyte antigen (HLA) molecules on the patient’s leukemia. However, the success of allo-HSCT in curing AML is hampered by disease recurrence, which is frequently due to selective loss of the patient-specific HLA by recurring leukemia posttransplantation (“HLA loss relapse”). In this project, 6 of the major European HSCT centres (each involved in translational research and clinical activity) will join in a combined bench-to-bedside effort aimed at developing new methodologies for early detection of HLA loss relapse, determining its frequency in different transplant settings, and identifying clinical and immunogenetic risk factors for the development of this leukemia variants. Results expected from this study will provide a unique platform for dissemination of novel technical and clinical know-how within Europe, and facilitate a significant step forward in the early detection and cure of leukemia.