Deferasirox (ICL670) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with ␤-thalassemia aged 2 years or older. Patients were randomized and received treatment with deferasirox (n ‫؍‬ 296) or deferoxamine (n ‫؍‬ 290), with dosing of each according to baseline liver iron concentration (LIC). The primary endpoint was maintenance or reduction of LIC; secondary endpoints included safety and tolerability, change in serum ferritin level, and net body iron balance. In both arms, patients with LIC values of 7 mg Fe/g dry weight (dw) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin, and effects on net body iron balance. However, the primary endpoint was not met in the overall population, possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw. The most common adverse events included rash, gastrointestinal disturbances, and mild nonprogressive increases in serum creatinine. No agranulocytosis, arthropathy, or growth failure was associated with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload. (Blood. 2006;107:3455-3462)

Patients with ␤-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged > 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received > 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with > 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ؎ 11.2 mg Fe/g dry weight (dw; n ‫؍‬ 103; P < .001) and 3.1 ؎ 7.9 mg Fe/g dw (n ‫؍‬ 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n ‫؍‬ 196; P < .001) and 371 ng/mL (n ‫؍‬ 147; P < .001), respectively, after > 4 years' exposure. Investigator-assessed, drugrelated adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with ␤-thalassemia suggests treatment for < 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials-.gov as #NCT00171210. (Blood. 2011; 118(4):884-893)

We aimed to study the effect of iron deficiency anemia (IDA) on immunity. In 32 children with IDA and 29 normal children, the percentage of T-lymphocyte subgroups, the level of serum interleukin-6 (IL-6); and the phagocytic activity, the oxidative burst activity of neutrophils and monocytes and the levels of immunoglobulins were compared. There was no difference in the distribution of T-lymphocyte subgroups. The mean IL-6 levels was 5.6+/-3.9 pg/ml in children with IDA and 10.3+/-5.3 pg/ml in the control group (P<0.001). The percentage of neutrophils with oxidative burst activity when stimulated with pma was 53.4+/-32.7% in children with IDA and 81.7+/-14.3% in the control group (P=0.005). The percentage of monocytes with oxidative burst activity was 13.8+/-11.7% in children with IDA and 35+/-20.0% in the control group (P<0.001) when stimulated with pma. and 4.3+/-3.1 versus 9.7+/-6.0% (P=0.008) when stimulated with fMLP. The ratio of neutrophils with phagocytic activity was 58.6+/-23.3% in the anemic group; and 74.2+/-17.7% in the control group (P=0.057). The ratio of monocytes with phagocytic activity was 24.3+/-12.0% in the anemic group; and 42.9+/-13.4% in the control group (P=0.001). IgG4 level was 16.7+/-16.6 mg/dl in children with IDA and 51.8+/-40.7 mg/dl in healthy children (P<0.05). These results suggest that humoral, cell-mediated and nonspecific immunity and the activity of cytokines which have an important role in various steps of immunogenic mechanisms are influenced by iron deficiency anemia.

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