Iron overload, a potentially serious consequence of multiple blood transfusions, can be effectively managed with chelation therapy. Deferasirox, an investigational once-daily oral chelator, has been evaluated in a 1 year study of iron-overloaded adult and pediatric patients (n=184) with transfusion-dependent anemia including β-thalassemia, myelodysplastic syndromes (MDS) and Diamond-Blackfan anemia (DBA). Patients were stratified into four daily dose groups (5, 10, 20 and 30 mg/kg) according to baseline liver iron concentration (LIC; 2–3, >3–7, >7–14 and >14 mg Fe/g dw, respectively). Iron balance was determined for all patients, based on transfusional iron intake and chelator-induced iron excretion, derived from the change in LIC during the study (Table 1).
Patient characteristics, LIC, serum ferritin and iron excretion/intake ratio during deferasirox treatment
| β-thalassemia (n=85) | DBA (n=30) | MDS (n=47) | Other anemias (n=22) | |
|---|---|---|---|---|
| *Mean ± SD | ||||
| Age*, years | 24.7 ± 10.0 | 16.1 ± 10.3 | 65.1 ± 12.5 | 35.8 ± 22.9 |
| Body weight, kg | 51.1 ± 14.1 | 39.1 ± 18.7 | 70.4 ± 12.5 | 56.1 ± 18.5 |
| Deferasirox dose*, mg/kg | 23.8 ± 7.2 | 23.6 ± 7.4 | 20.0 ± 8.3 | 21.9 ± 6.5 |
| Iron intake*, mg/kg/day | 0.35 ± 0.12 | 0.40 ± 0.11 | 0.28 ± 0.14 | 0.31 ± 0.19 |
| <0.3, n (%) | 28 (33) | 6 (20) | 25 (53) | 10 (45) |
| 0.3–0.5, n (%) | 49 (58) | 19 (63) | 20 (43) | 7 (32) |
| >0.5, n (%) | 8 (9) | 5 (17) | 2 (4) | 5 (23) |
| Serum ferritin*, ng/mL | ||||
| Baseline | 4321 ± 2881 | 3245 ± 2439 | 3343 ± 1978 | 3144 ± 1850 |
| Absolute change | −386 ± 1626 | −118 ± 1373 | −268 ± 2053 | −750 ± 1517 |
| LIC*, mg Fe/g dw | (n=76) | (n=26) | (n=28) | (n=17) |
| Baseline | 19.3 ± 10.9 | 18.8 ± 10.7 | 15.6 ± 11.9 | 15.1 ± 6.2 |
| Absolute change | −4.7 ± 8.6 | −1.6 ± 6.5 | −5.7 ± 6.3 | −3.7 ± 6.3 |
| Iron excretion/intake ratio | 1.5 ± 0.90 | 1.1 ± 0.46 | 1.7 ± 0.93 | 1.6 ± 1.48 |
| β-thalassemia (n=85) | DBA (n=30) | MDS (n=47) | Other anemias (n=22) | |
|---|---|---|---|---|
| *Mean ± SD | ||||
| Age*, years | 24.7 ± 10.0 | 16.1 ± 10.3 | 65.1 ± 12.5 | 35.8 ± 22.9 |
| Body weight, kg | 51.1 ± 14.1 | 39.1 ± 18.7 | 70.4 ± 12.5 | 56.1 ± 18.5 |
| Deferasirox dose*, mg/kg | 23.8 ± 7.2 | 23.6 ± 7.4 | 20.0 ± 8.3 | 21.9 ± 6.5 |
| Iron intake*, mg/kg/day | 0.35 ± 0.12 | 0.40 ± 0.11 | 0.28 ± 0.14 | 0.31 ± 0.19 |
| <0.3, n (%) | 28 (33) | 6 (20) | 25 (53) | 10 (45) |
| 0.3–0.5, n (%) | 49 (58) | 19 (63) | 20 (43) | 7 (32) |
| >0.5, n (%) | 8 (9) | 5 (17) | 2 (4) | 5 (23) |
| Serum ferritin*, ng/mL | ||||
| Baseline | 4321 ± 2881 | 3245 ± 2439 | 3343 ± 1978 | 3144 ± 1850 |
| Absolute change | −386 ± 1626 | −118 ± 1373 | −268 ± 2053 | −750 ± 1517 |
| LIC*, mg Fe/g dw | (n=76) | (n=26) | (n=28) | (n=17) |
| Baseline | 19.3 ± 10.9 | 18.8 ± 10.7 | 15.6 ± 11.9 | 15.1 ± 6.2 |
| Absolute change | −4.7 ± 8.6 | −1.6 ± 6.5 | −5.7 ± 6.3 | −3.7 ± 6.3 |
| Iron excretion/intake ratio | 1.5 ± 0.90 | 1.1 ± 0.46 | 1.7 ± 0.93 | 1.6 ± 1.48 |
Transfusion requirements and iron intake during the study varied widely between diseases. However, LIC and serum ferritin decreases were consistently achieved in all patient groups. More than one-third (38%) of patients, most of whom had MDS or other anemias, had an iron intake rate <0.3 mg/kg/day (average: 0.2 mg/kg/day; corresponding to 5.6 ml RBC/kg/month). In these patients, deferasirox at 10 and 20 mg/kg reduced LIC.
Overall, an iron intake- and dose-related response pattern was observed for both LIC and serum ferritin (Figure 1).
Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year
Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year
According to these results, deferasirox demonstrates the ability to stabilize and effectively decrease body iron levels at doses of 10, 20 and 30 mg/kg/day, depending on the degree of iron intake. In conclusion, dosing of chelation therapy should be guided by a patient’s transfusion requirements and the treatment goal, which is either to maintain or reduce body iron.