Red blood cell transfusions are still the cornerstone of supportive care in many hemato-oncological patients. A chronic and underestimated side-effect of red blood cell transfusions is iron overload, which is associated with increased morbidity and mortality. This thesis focuses on red blood cell transfusion strategies and the management of iron overload due to frequently administered red blood cell transfusions. A nationwide survey showed a large variation in red blood cell transfusion practice throughout the Netherlands. This is probably due to the lack of high grade evidence-based guidelines. In a meta-analysis was demonstrated that a restrictive red blood cell transfusion strategy was safe and could lead to fewer side-effects and reduced costs in hemato-oncological patients. In order to diagnose iron overload, tissue biopsy is still the golden standard. Due to its risk of complications, tissue biopsies are not likely to be performed in this patient group. In this thesis, we assessed the value of bone marrow iron scores in frequently transfused acute myeloid leukemia patients. We concluded that bone marrow iron scores on routinely performed bone marrow aspirate specimens could guide iron-lowering therapy and/or transfusion strategies in an early stage. Finally, in a large European registry we showed that toxic iron species as non-transferrin bound iron and labile plasma iron are associated with inferior overall survival in lower-risk myelodysplastic syndrome patients. Likewise, treatment with iron chelation therapy led to an improvement in overall and progression-free survival in lower-risk myelodysplastic syndrome patients. Sanquin Blood SupplyLUMC / Geneeskund