BackgroundIron deficiency is the most common disorder in the world, affecting approximately 25% of the world`s population and the most common cause of anemia.ObjectiveTo evaluate the efficacy and safety of intravenous iron sucrose (IS) in the treatment of adults with iron deficiency anemiaMethodsEighty-six adult patients with iron deficiency anemia, who had intolerance or showed no effect with oral iron therapy, received a weekly dose of 200 mg of intravenous iron sucrose until the hemoglobin level was corrected or until receiving the total dose of intravenous iron calculated for each patientResultsThe mean hemoglobin and serum ferritin levels were 8.54 g/dL and 7.63 ng/mL (pre-treatment) and 12.1 g/dL and 99.0 ng/mL (post-treatment) (p-value < 0.0001), respectively. The average increases in hemoglobin levels were 3.29 g/dL for women and 4.58 g/dL for men; 94% of male and 84% of female patients responded (hemoglobin increased by at least 2 g/dL) to intravenous iron therapy. Correction of anemia was obtained in 47 of 69 (68.1%) female patients and in 12 of 17 male (70.6%) patients. A total of 515 intravenous infusions of iron sucrose were administered and iron sucrose was generally well tolerated with no moderate or serious adverse drug reactions recorded by the investigators.ConclusionsOur data confirm that the use of intravenous iron sucrose is a safe and effective option in the treatment of adult patients with iron deficiency anemia who lack satisfactory response to oral iron therapy. Intravenous iron sucrose is well tolerated and with a clinically manageable safety profile when using appropriate dosing and monitoring. The availability of intravenous iron sucrose would potentially improve compliance and thereby reduce morbidities from iron deficiency.

The efficacy and safety of a 2-year treatment with deferasirox was evaluated in 31 patients with sickle cell anemia and transfusional iron overload. At 24 months, there were significant decreases from baseline in mean serum ferritin (from 2,344.6 to 1,986.3 µg/l; p = 0.040) and in mean liver iron concentration (from 13.0 ± 5.4 to 9.3 ± 5.7 mg Fe/g dry weight; p < 0.001). Myocardial T2* values were normal (>20 ms) in all patients at baseline and did not change significantly over the course of the study. However, there was a significant improvement from baseline in left ventricular ejection fraction at 24 months (62.2–64.6%; p = 0.02). Deferasirox was generally well tolerated with no progressive increases in serum creatinine or renal failure observed. These data confirm that deferasirox is effective in reducing body iron burden in patients with sickle cell anemia and transfusional iron overload.

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5148 Background: Majority of patients with sickle cell disease receive repeated blood transfusions by adulthood. Because the body has no physiological mechanism to actively excrete excess iron, chelation therapy is important for the management of iron overload and its complications, including iron deposition into the liver, heart and endocrine organs, eventual death. Deferasirox (DFX) is a once-daily, oral iron chelator that is approved as first-line treatment of chronic transfusional iron overload. Its safety, tolerability and efficacy in reducing body iron burden have been demonstrated in patients with β-thalassaemia major and in other chronic transfusion-dependent anaemias, including SCD. Aims and Methods: Objectives of this prospective, non-randomised, phase IV trial were to evaluate the iron overload status, before and after two year-treatment with DFX, using liver iron concentration [LIC, mg/d dry weight (dw)] by magnetic resonance imaging (MRI) hepatic, MRI cardiac (Cardiac T2*, ms), serum ferritin (SF, μ g/L), and to evaluate the safety and tolerability of DFX. Results: A total of 31 patients with SCD and iron overload, defined as the use of ≥ 20 units of RBC units and/or two SF levels ≥ 1000 μ g/L during the 6 months preceding enrollment, received starting dose of 20mg/kg/day of DFX. Efficacy was assessed monthly by measuring change from baseline in SF levels. Safety was evaluated on a monthly basis according to the incidence and type of adverse events and measurement of laboratory parameters, including serum creatinine and liver enzyme levels. Two patients discontinued treatment at 8 and 9 months, due to pregnancy and moving to other city, respectively. One patient died at 18 months due to pulmonary infection and hemorrhagic stroke. DFX was interrupted in 3 patients due to confirmed SF levels <500 μ g/L at 18-month period of treatment and DFX was not reinstated in none of them during the final 6 months of study. Twenty-five patients completed 2-year treatment. Mean ± SD age 26.9 ± 12.5y; 84% female, 90% afrodescendent, 61.3% on regular blood transfusion; median (range) DFX dose over 24 months and DFX exposure were 20 mg/kg/day (15-25) and 90.5 weeks (35.6-98.0), respectively. Mean SF level (μ g/L) did not significantly reduced at 12 months (p=0.052) but significantly dropped at 24 months compared to baseline [from 2344.6 to 1986.3 (p=0.040)]. Mean ± SD LIC significantly dropped at 12 months and at 24 months compared to baseline [from 13.0 ± 5.4 to 10.4 ± 6.3 (p=0.001) and to 9.3 ± 5.7 (p<0.001), respectively]. The proportion of patients with LIC levels (mg/g dw) ≤7.0, >7.0- ≤14.0 and >14.0 from baseline to 24 months by percentage of patients changed from 13.6% to 44.0%, 40.9% to 44.0% and 45.5% to 12.0%, respectively. In all patients, Cardiac T2* was normal (> 20 ms) at baseline, 12 and 24 months of treatment. There was no significant difference between left ventricular ejection fraction values at baseline and after 12 months but this parameter significantly increased at 24 months of treatment compared to baseline [from 62.2 ± 6.0 to 64.6 ± 6.2 (p=0.02)]. The most common drug-related AEs were mild, transient diarrhea (7 pts), headache (7), nausea (5), vomiting (3), skin rash (2), increases in ALT (2), serum creatinine increases that exceeded the ULN (2). No patient experienced progressive increases in serum creatinine or renal failure. Conclusions: Our data confirms that deferasirox is effective in reducing body iron burden in transfused patients with SCD, well tolerated in pediatric and adult patients and with a clinically manageable safety profile. The availability of deferasirox as a once-daily, oral iron chelator would potentially facilitate improved compliance, and thereby reduce morbidity and mortality from iron overload. Disclosures: No relevant conflicts of interest to declare.

The majority of patients with sickle cell anaemia have received repeated blood transfusions by adulthood. Because the body has no physiological mechanism to actively excrete the excess of iron, chelation therapy is important for the management of iron overload and its complications, including iron deposition into the liver, heart and endocrine organs, eventual death. While studies are limited, progressive iron loading and subsequent tissue injury in sickle cell disease appears similar to other transfused populations. Deferasirox (Exjade, ICL670) is a once-daily, oral iron chelator that is approved for the first-line treatment of chronic transfusional iron overload. Its safety, tolerability and efficacy in reducing body iron burden have been demonstrated in patients with β-thalassaemia major and in other chronic transfusion-dependent anaemias. The objectives of this prospective, non-randomised, phase IV trial were to evaluate the iron overload status, before and after one year-treatment with deferasirox, using liver iron concentration (LIC) by MRI of the liver, MRI cardiac (Cardiac T2*), serum ferritin and the impact of deferasirox treatment on these measurements, and to evaluate the safety and tolerability of this drug. A total of 30 patients with sickle cell anemia and iron overload, defined as the use of ≥ 20 units of RBC units and/or two plasma ferritin levels ≥ 1000 mcg/L during the 6 months preceding enrollment, received starting dose of 20mg/kg/day of deferasirox. Efficacy was assessed monthly by measuring change from baseline in serum ferritin levels. Safety was evaluated on a monthly basis according to the incidence and type of adverse events and measurement of laboratory parameters, including serum creatinine and liver enzyme levels. Mean (range) age 26.4 ± 12.3y (9–49), 83% female, 93% afrodescendent, 60% on regular blood transfusion, mean deferasirox exposure 30.1 ± 5.6 weeks (16–39), mean MRI hepatic (LIC, μmol/g) 233.0 ± 98.8 (45 – 350), mean MRI cardiac (Cardiac T2*, ms) 41.20 ± 5.46 (27.52 – 51.19). Median ± SD and mean (range) serum ferritin level (mcg/L) at baseline and 6 months varied from 2315.5 ± 1083.9 to 2062.5 ± 1320.8 (p=0.032) and 2012.0 (1013–6074) to 1654.0 (688–6729), respectively. The proportion of patients with serum ferritin levels &lt; 2000, 2000- &lt;3000 and ≥ 3000 mcg/L from baseline to 6 months by percentage of patients changed from 50% to 60%, 26.7% to 26.7% and 23.3% to 13.3%, respectively. The most common drug-related AEs were mild, transient diarrhea (23.3%), headache (20.0%) and nausea (16.7%). Maculo-papular skin rash and serum creatinine increases upper limit of normal were observed in 2 (6.7%) patients. No patient experienced progressive increases in serum creatinine or renal failure. Our preliminary data, over 6-month-period of treatment, confirms that deferasirox is effective and generally well tolerated in pediatric and adult patients, and appears to have similar efficacy to deferoxamine in reducing body iron burden in transfused patients with sickle cell anemia. The availability of deferasirox as a once-daily, oral alternative would potentially facilitate improved compliance, and thereby reduce morbidity and mortality from iron overload.