Thalassemia is a severe hereditary blood disorder that leads to chronic anemia and life-long blood transfusion dependence and reduced life expectancy. Children with severe thalassemia can be cured with a stem cell transplantation. In this treatment, the unhealthy blood stem cells are replaced by blood stem cells from a healthy donor. Unfortunately, transplant fails in one out of five thalassemia patients. Then, a second HSCT procedure is needed. It is unclear why transplant failure occurs so often in thalassemia patients. Earlier research showed that the bone marrow of thalassemia patients is a hostile environment for healthy stem cells. In this study, we will investigate the role of bone marrow macrophages in thalassemia transplant failure. Macrophages are immune cells that are important to maintain stem cells and support red blood cell production. In particular, we will study whether, when intoxicated with iron as in thalassemia, macrophages have a negative impact on donor blood production. The knowledge from this project will contribute to better treatment of patients with thalassemia and other severe blood diseases.