Clinical and Biological Characterization of Patients with Low/Intermediate-1 Risk Myelodysplastic Syndrome and Iron Overload

Abstract 4956 Introduction. Patients with Myelodysplastic Syndrome (MDS) are susceptible to developing iron overload as a response to the red blood cell (RBC) transfusions and ineffective hematopoiesis. This iron overload (IOL) is characterized by an increase in oxygen-reactive species accompanied by a decrease in antioxidants, and results in hepatic, cardiac and endocrine disorders, as well as an increased risk of infection. Ineffective hematopoiesis promotes iron absorption at intestinal level. This process is enhanced by the presence of mutations in the hereditary hemochromatosis gene (HFE). This study aims to define the features that accompany patients with iron overload, comparing them to a MDS population at diagnosis. Patients and methods. 34 low/int-1 MDS patients (International Prognostic Score System, IPSS) were assessed, 22 of them at diagnosis and 12 patients when IOL was developed. Peripheral blood samples were drawn after informed consent was obtained from the patient or the patient′s guardians in accordance with the Declaration of Helsinki. The analyzed parameters were: WHO classification, sex, age, blood count, number of RBC units received, iron metabolism, and mutations of the HFE gene. Liver damage was estimated by measuring Alanine transaminase (ALT) levels, and liver iron concentration (LIC) detected by Magnetic Resonance (MR). Likewise, levels of labile plasmatic iron (LPI) (eLPI Assay Kit, Aferrix) were quantified by spectrofluorimetric determination. Oxidative damage was assessed by quantifying the modified base 8-oxo-2-hydroxi-deoxiguanosine (8-oxo-dG) by means of High-Performance Liquid Chromatography (HPLC) and the O 2 − anion levels by flow cytometry. Results. According to the WHO classification, 72. 2% of cases with MDS and IOL assessed belonged to Refractory Sideroblastic Anemia (RSA) group, unlike 27. 3% of patients at diagnosis (p=0. 0265). In comparison to diagnosis patients, IOL subjects presented lower mean age (76 vs. 81 years; p=0. 0172), hemoglobin levels (7. 5 ± 0. 4 vs. 10. 3 ± 0. 3 g/dl; p vs. 3. 0 ± 0. 1×10 9 /l; p vs. 219 μg/dl; p vs. 31. 5%; p vs. 11. 0 U/l; p=0. 0263) were observed when compared to the diagnosis patients. On the other hand, among IOL patients the average levels for LIC were 13. 8 ± 2. 0 mg Fe/g (normal levels vs. 0. 1 U; p 2 − anions (p=0. 0157) was observed. Conclusions. Patients with IOL show alterations in their hematological and iron metabolism parameters, liver damage and high LPI levels. IOL is associated with increased oxidative damage at DNA level and production of superoxide radicals. There are cases of IOL patients who are not transfusion dependent, where the presence of RSA and HFE gene mutations plays a determining role. Patients with IOL can benefit from effective chelation therapy that reduces the harmful effects of iron. Disclosures: Carbonell: Novartis Farmaceutica, S. A.: Research Funding; Universitat de Valencia: Research Funding.