The effect of blood transfusion therapy on fatigue in patients with Myelodysplastic SyndromeDr Callum Brownstein

Supervisors: Pr Guillaume MILLET & Dr Denis GUYOTAT

What are Myelodysplastic Syndromes?

Myelodysplastic syndromes (MDS) are a group of cancers characterised by ineffective production of blood cells. MDS occurs as a result of mutations taking place in the bone marrow, where cells responsible for the production of mature healthy blood cells are situated. As a result, MDS primarily manifests as a reduced number of mature blood cells, known as cytopenia. The most common cytopenia in patients with MDS is a reduction in the number of red blood cells, which are responsible for delivering oxygen inhaled through the lungs to other parts of the body, such as the muscles, brain and other organs.

Although MDS can affect people of any age, it is most common in older people, with the average age of MDS diagnosis occurring at 70-75 years of age. It has been estimated that in people aged ≥ 65 years, between 75 and 162 per 100,000 are diagnosed with MDS. The symptoms of MDS vary considerable between patients, with some patients displaying no symptoms and a life expectancy similar to the normal population, and other patients displaying severe symptoms and a risk of developing leukemia. As a result, patients with MDS are grouped into low- and high-risk based on their symptoms and relevant clinical variables, with most patients (around 80%) belonging to the low-risk category.

Fatigue in MDS

The most common symptom in MDS patients is fatigue, which has been reported by over 90% of patients. This symptom, characterized by sensations of tiredness and weakness and limitations in functional capacity, is unrelated to previous activity, and can have serious and distressing physical and emotional implications. As fatigue in MDS is strongly linked with a reduced quality of life, as well as inactivity and depression, identifying the factors which contribute to fatigue and implementing strategies in an attempt to reduce fatigue is an important area of research.

Fatigue in MDS, as with other chronic health conditions, is complex and unlikely to be induced by a single cause. However, one of the primary candidates contributing to fatigue is anemia. The reduced number of red blood cells associated with anemia increases the demand on the heart and lungs to sustain adequate oxygen supply during rest and physical activity, while also increasing metabolic stress in the muscles during normal daily activities, such as walking, climbing stairs, or carrying shopping bags. While anemia is linked to fatigue in MDS, it does not entirely explain the fatigue experienced by patients, and a better understanding of the causes of fatigue in MDS is required. Other potential physiological and psychological contributors to fatigue, such as inflammation, oxidative stress, impaired vascular function, depression and sleep disturbances, require further investigations.

The effect of blood transfusion therapy on fatigue in MDS patients

Blood transfusion is the process of transferring blood into the circulation through the veins to replace lost components of blood. More than 80% of patients with MDS receive blood transfusion throughout the course of the disease to increase red blood cell count and reduce symptoms associated with anemia, such as fatigue. While transfusions have been reported to reduce fatigue in MDS patients, the symptom is not eliminated in all patients following transfusion. It is unclear why fatigue persists in many patients despite an improvement in the number of red blood cells. In light of this uncertainty, our study will assess the effects of blood transfusion therapy on fatigue in MDS patients, and attempt to determine why some patients are still fatigued following transfusions. We will measure a comprehensive group of physiological and psychological variables, such as red blood cell count, inflammation, oxidative stress, vascular function, quality of life, sleep disturbances and exercise capacity. Patients will have all of these measures taken before and after their blood transfusion, as well as being assessed for their level of fatigue. We will then determine whether fatigue improves following transfusion, and whether there is an association between an improvement in fatigue and any of the range of physiological variables measured. The results of the study will improve understand of the causes of fatigue in MDS patients, and could be used to guide future research attempting to reduce fatigue in MDS patients, particularly those who don’t display a reduction in fatigue following blood transfusion therapy.