An association between compatible but ABO non-identical red blood cell (RBC) transfusions and increased in-hospital mortality was identified in an observational study. A review of the literature was performed to explore plausible biological mechanisms and inflammation was chosen. This thesis describes a body of work that was performed to develop a PICOT research question and design a pilot feasibility randomized crossover trial in patients with myelodysplastic syndrome (MDS) to determine whether there is evidence of an inflammatory response resulting from transfusion of ABO non-identical RBCs compared with the transfusion of ABO identical RBCs. The work undertaken as part of this thesis included: identifying a theoretical framework to guide the selection of outcome measures that would detect inflammation; identifying an appropriate and feasible population to study; designing the feasibility pilot study to answer the research question that was developed; and a discussion of ethical issues that were considered as the design of the pilot study was developed. The work that was done to develop the elements of PICOT resulted in the following research question: Is it feasible to perform a randomized crossover trial in chronically transfused blood group A patients with myelodysplastic syndrome (MDS), that looks for laboratory evidence of inflammation (in vitro biomarkers measured at baseline and pre-specified times between 1 and 96 hours post transfusion), following the transfusion of group O RBCs (ABO non-identical) compared to transfusion of group A (ABO identical) RBCs? / Thesis / Master of Science (MSc)