Does G6PD-Deficiency Related Oxidative Stress and Hemolysis Affect Erythroid Response to Erythropoietic Stimulating Agents (ESA) in Myelodysplastic Patients?

Abstract

Background: Anemia is the most frequent cytopenia in Myelodysplastic Syndrome (MDS). Epoetin alfa, Epoetin beta and Darbepoetin alfa (ESA) have been investigated in several studies as useful to treat anemia in this category of patients. Available preclinical data support oxidative stress and hemolysis contributing to ESA resistance but not clinical data is today available. G6PD deficiency is an X-linked condition characterized by a markedly reduced capability to protect red blood cells from oxidative stresses. In the island of Sardinia the prevalence is reported to be as high as 12%. Patients and Methods: We retrospectively analyzed all MDS patients who had received ESA in our centre. Diagnosis of MDS was made according to WHO criteria. Patients were stratified based on International Prognostic Scoring System (IPSS). At diagnosis baseline EPO level and G6PD quantitative estimation were detected. G6PD deficiency was defined as an enzyme dosage of less than 0.96 UI/g of Hb in the peripheral blood. Red blood cell (RBC) transfusions requirement before starting treatment was evaluated. Erythroid hematologic improvement (HI-E) was evaluated according to the International Working Group (IWG) response criteria ( Cheson et al JCO 2006). Results: Thirty patients met the above specified criteria. Table 1 showed patients’ characteristics. Of them 7 were G6PD-defiecient and 23 had normal G6PD level values. Twenty four patients (80%) achieved an HI-E (14 major and 10 minor). In the G6PD-deficient group HI-E was observed in 7 over 7 patients ( major in 4 and minor in 3). In the control group HI-E was observed in 17 over 23 patients (major in 10 minor in 7). (P= 0.29). Conclusions: We evaluated 30 MDS lowrisk and Int I IPSS patients who received ESA in the last 20 years in our centre. Despite the common belief that oxidative stress and hemolysis may contribute to ESA resistance, no statistically significant difference to potentially resistance to ESA treatment in G6PD deficiency have been observed. We conclude that G6PD-deficiency does not contraindicate the use of ESA in this setting of patients.