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ABSTRACT: Plasma markers in addition to serum ferritin (SF) may be useful for the assessment of iron overload; however, predictive utility may differ depending on underlying, transfusion-dependent, anemias. Data were collected before and after 1 year of deferasirox treatment (end of study; EOS) from the large, 1-year EPIC (Evaluation of Patients' Iron Chelation with Exjade(®) ) study. Trends were evaluated between liver iron concentration (LIC), transferrin saturation (TfSat), pre-dose labile plasma iron (LPI) and their relationship to SF categories in 1530 patients: thalassemia major (TM; n=1114), myelodysplastic syndromes (MDS, n=336) and sickle cell disease (SCD, n=80). Baseline and EOS SF values showed a clear and similar relationship to LIC for all disease groups. TfSat also showed a relationship to SF, most clearly in SCD patients, where TfSat was lowest in the lowest relative SF category. Unlike SF or LIC, TfSat did not decrease at EOS in any disease group. Baseline LPI was raised in TM and MDS, but not in SCD patients, decreasing at EOS in both patient groups. After 1 year of chelation therapy, there was a significant trend for greater LPI reduction in TM patients achieving LIC <7 mg Fe/g dw (P=0.0137). Despite limitations, SF showed the clearest relationship, of the plasma markers evaluated, to LIC before and after 1 year of deferasirox in TM, MDS and SCD patients. In TM patients, changes in LPI with chelation show a significant relationship to EOS LIC and may provide an additional indicator of chelation response (clinicaltrials. gov identifier: NCT00171821). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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ABSTRACT: Background Following a clinical evaluation of deferasirox (Exjade) it was concluded that, in addition to baseline body iron burden, ongoing transfusional iron intake should be considered when selecting doses. The 1-year EPIC study, the largest ever investigation conducted for an iron chelator, is the first to evaluate whether fixed starting doses of deferasirox, based on transfusional iron intake, with dose titration guided by serum ferritin trends and safety markers, provides clinically acceptable chelation in patients (aged >or=2 years) with transfusional hemosiderosis from various types of anemia. DESIGN AND METHODS: The recommended initial dose was 20 mg/kg/day for patients receiving 2-4 packed red blood cell units/month and 10 or 30 mg/kg/day was recommended for patients receiving less or more frequent transfusions, respectively. Dose adjustments were based on 3-month serum ferritin trends and continuous assessment of safety markers. The primary efficacy end-point was change in serum ferritin after 52 weeks compared with baseline. RESULTS: The 1744 patients enrolled had the following conditions; thalassemia (n=1115), myelodysplastic syndromes (n=341), aplastic anemia (n=116), sickle cell disease (n=80), rare anemias (n=43) and other transfused anemias (n=49). Overall, there was a significant reduction in serum ferritin from baseline (-264 ng/mL; P<0.0001), reflecting dosage adjustments and ongoing iron intake. The most common (>5%) adverse events were gastrointestinal disturbances (28%) and skin rash (10%). Conclusions Analysis of this large, prospectively collected data set confirms the response to chelation therapy across various anemias, supporting initial deferasirox doses based on transfusional iron intake, with subsequent dose titration guided by trends in serum ferritin and safety markers (clinicaltrials.gov identifier: NCT00171821).
Hôpital Henri Mondor (Hôpitaux Universitaires Henri Mondor)Créteil, Île-de-France, France