Informing the design of an age of blood crossover randomized controlled trial in patients with Myelodysplastic syndromes to study change in quality of life as a response to RBC transfusion

Abstract

Patients with myelodysplastic syndromes (MDS) frequently receive red blood cell (RBC) transfusions to alleviate symptoms of anemia and improve health-related quality of life (HR-QoL). Patients can sometimes continue to feel unwell after transfusion and the age of the transfused RBCs could contribute to this observation. Three pilot studies were conducted to inform the design of a randomized crossover trial to determine if fresh blood to MDS patients could improve HR-QoL post-transfusion. A systematic review was performed to inform the background and rationale for the trial. The results showed a dearth of literature addressing the research question. Only two clinical trials have been conducted to date where fatigue and HR-QoL were the primary outcomes of interest. Although results of the trials were negative, several limitations and generalizability issues warrant additional research in this area. Crossover designs necessitate patients have a stable prognosis while being observed; hence, a chart review of adult MDS patients was conducted to assess clinical stability using the following criteria: interval of days between transfusions; pre-transfusion Hb; number of hospital admissions; and severe infections. Results indicated that the majority of patients who had received greater than 3 transfusions within the 6-month observation period had stable disease and were appropriate for a crossover trial. The criteria defining stability will be useful for identifying eligible patients. Finally, an applied qualitative study in adult MDS patients in Hamilton was conducted to inform the selection of an appropriate outcome measure (i.e. HR- QoL tool). Short semi-structured interviews were conducted with participants to elicit information about anemia related symptoms and changes in well-being in response to transfusion. The results of the study support clinical observations that suggest patients do not immediately recover post-transfusion. Findings indicate that an appropriate HR-QoL tool should be short, be disease specific, and have a short recall period. Currently, the Quality of Life-E tool, validated in patients with MDS, fits most of these criteria. In conclusion, data from the systematic review and the two pilot studies suggest that it may be feasible to conduct an age of blood crossover trial in MDS patients where the primary outcome of interest is HR-QoL.