Safe and Efficient Chelation by Deferasirox In Thalassemia Major Patients with Low Liver and Cardiac Iron Concentrations

Abstract 5168

Chelation treatment of iron overload from chronic blood (RBC) transfusion is still a challenge to both, patients and medical caretakers. Different treatment regimes have been recommended so far, especially for chronically transfused patients with low or even normal liver iron concentration. We report the results from 16 regularly transfused patients with thalassemia major (TM) who were on iron chelation treatment under normal to mild liver iron concentration (LIC). All patients received deferoxamine (DFO) treatment before they changed to deferasirox (DSX) treatment.

16 TM patients (mean age 13.6 y) were treated with DSX (median dose 18 mg/kg/d, range: 7 – 33 mg/kg/d) for 6 to 71 months. Liver iron measurements by biomagnetic susceptometry (BLS) and/or MRI-R2 as well as cardiac MRI-R2* were performed in intervals of 6 to 12 months. The median LIC was 782 μ g/g-liver wet weight (range: 460 μ g – 1122 μ g). Median RBC transfusion rate was 8500 ml/y, equivalent to about 2 erythrocyte concentrates per 3 weeks or a daily iron influx of 16.2 mg/d. For each measurement interval, the ratio of daily iron influx and DSX dose rate was calculated. This represents the equilibrium molar efficacy for iron balance.

In all 16 TM patients no severe side effects were observed and creatinine was in the normal range of < 0.9 mg/d throughout the treatment with DSX. From baseline DFO treatment interval to the endpoint of DSX treatment, liver iron decreased by 124 – 4689 μ g/g-liver (conversion factor of 6 for mg/g-dry-wgt), while serum ferritin decreased by -596 to 8283 μ g/l. For all measurement intervals, molar chelation efficacies between 18 % and 56 % were calculated at equilibrium with a median efficacy of 31 % (interquartile range = 16 %). This agrees with molar efficacies of DSX reported earlier, but for relatively higher LIC and chelation doses (Blood 2005; 106(11):#2690 and Blood 2007; 110(11):#2776). The cardiac R2* (median R2* = 38 s^-1) was either below the normal threshold of 50 s^-1 (T2* > 20 ms) or decreased by about 24 %/y under DSX treatment. In these few patients at low LIC, this was even higher than recently reported.