Therapy with RBC transfusions and rHuEPO for management of anemia in patients with myelodysplastic syndromes causes recurrent fluctuations in hemoglobin levels. The purpose of this study was to elaborate a mathematical model for the interpretation of hemoglobin fluctuations and to correlate the resulting numerical parameter (Variaglobin Index) with quality of life and fatigue. In 32 myelodysplastic patients, lower amplitude of the Variaglobin Index was found significantly correlated with a better quality of life and less fatigue. The mathematical model proposed here makes it easy to monitor anemia in myelodysplastic patients and to adjust therapy accordingly.