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Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study.

Porter J, Galanello R, Saglio G, Neufeld EJ, Vichinsky E, Cappellini MD, Olivieri N, Piga A, Cunningham MJ, Soulières D, Gattermann N, Tchernia G, Maertens J, Giardina P, Kwiatkowski J, Quarta G, Jeng M, Forni GL, Stadler M, Cario H, Debusscher L, Della Porta M, Cazzola M, Greenberg P, Alimena G, Rabault B, Gathmann I, Ford JM, Alberti D, Rose C - Eur. J. Haematol. (2007)

Bottom Line: There were no disease-specific safety/tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases.Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias.There were no disease-specific adverse events.

View Article: PubMed Central - PubMed

Affiliation: University College London, London, UK. j.porter@ucl.ac.uk

ABSTRACT

Objectives/methods: This 1-yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3-81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond-Blackfan anaemia (DBA; n = 30), other rare anaemias (n = 22) or beta-thalassaemia (n = 85). Dosage was determined by baseline liver iron concentration (LIC).

Results: In patients with baseline LIC > or = 7 mg Fe/g dry weight, deferasirox initiated at 20 or 30 mg/kg/d produced statistically significant decreases in LIC (P < 0.001); these decreases were greatest in MDS and least in DBA. As chelation efficiency and iron excretion did not differ significantly between disease groups, the differences in LIC changes are consistent with mean transfusional iron intake (least in MDS: 0.28 +/- 0.14 mg/kg/d; greatest in DBA: 0.4 +/- 0.11 mg/kg/d). Overall, LIC changes were dependent on dose (P < 0.001) and transfusional iron intake (P < 0.01), but not statistically different between disease groups. Changes in serum ferritin and LIC were correlated irrespective of disease group (r = 0.59), supporting the potential use of serum ferritin for monitoring deferasirox therapy. Deferasirox had a safety profile compatible with long-term use. There were no disease-specific safety/tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases.

Conclusions: Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias. There were no disease-specific adverse events. Once differences in transfusional iron intake are accounted for, dose-dependent changes in LIC or serum ferritin are similar in MDS and other disease groups.

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Iron excretion across dose and disease groups. The average iron excretion in mg/kg/d (±SD) is shown by disease group for doses above 5 mg/kg/d. There is a dose effect on iron excretion (P < 0.001), with no statistically significant difference in disease groups (P = 0.14). The overall average iron excretion is 0.22, 0.44 and 0.53 mg/kg/d for doses of 10, 20 and 30 mg/kg/d, respectively.
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fig02: Iron excretion across dose and disease groups. The average iron excretion in mg/kg/d (±SD) is shown by disease group for doses above 5 mg/kg/d. There is a dose effect on iron excretion (P < 0.001), with no statistically significant difference in disease groups (P = 0.14). The overall average iron excretion is 0.22, 0.44 and 0.53 mg/kg/d for doses of 10, 20 and 30 mg/kg/d, respectively.

Mentions: Average iron intake per kilogram of body weight varied widely both within and between disease groups (Table 1). On an average, patients with MDS had the lowest transfusional iron intake (0.28 mg/kg/d), while those with DBA had the highest (0.40 mg/kg/d). These differences in transfusional iron intake were also reflected in the proportions of patients having the lowest transfusional iron intake, with 53% of MDS patients, but only 20% of DBA patients requiring <0.3 mg/kg/d. At 20 and 30 mg/kg/d, deferasirox stabilised or reduced mean LIC and serum ferritin levels across a variety of transfusion-dependent anaemias (Table 2). However, changes in LIC were most pronounced in MDS (−9.4 mg Fe/g dw at 30 mg/kg/d) and least pronounced in DBA (−3.2 mg Fe/g dw at 30 mg/kg/d) and paralleled the relative changes in serum ferritin of −1581 and −143 μg/L, respectively. When including dose, iron intake category, disease group and the interaction of iron intake and disease group into an exploratory linear regression model, only dose (P < 0.001) and iron intake category (P < 0.01) had a statistically significant effect on change in LIC (P = 0.15 for disease group, P = 0.61 for interaction term). The same was observed when evaluating iron excretion (mg/kg/d) as the dependent variable, with no difference between disease groups but a statistically significant dose effect (P < 0.001, Fig. 2). Furthermore, iron-chelating efficiency is essentially the same in MDS and other patient groups (Table 2). These results therefore show that in addition to dose, the degree of transfusional iron intake is a key factor governing the outcome of iron chelation therapy across different diseases.


Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study.

Porter J, Galanello R, Saglio G, Neufeld EJ, Vichinsky E, Cappellini MD, Olivieri N, Piga A, Cunningham MJ, Soulières D, Gattermann N, Tchernia G, Maertens J, Giardina P, Kwiatkowski J, Quarta G, Jeng M, Forni GL, Stadler M, Cario H, Debusscher L, Della Porta M, Cazzola M, Greenberg P, Alimena G, Rabault B, Gathmann I, Ford JM, Alberti D, Rose C - Eur. J. Haematol. (2007)

Iron excretion across dose and disease groups. The average iron excretion in mg/kg/d (±SD) is shown by disease group for doses above 5 mg/kg/d. There is a dose effect on iron excretion (P < 0.001), with no statistically significant difference in disease groups (P = 0.14). The overall average iron excretion is 0.22, 0.44 and 0.53 mg/kg/d for doses of 10, 20 and 30 mg/kg/d, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2268958&req=5

fig02: Iron excretion across dose and disease groups. The average iron excretion in mg/kg/d (±SD) is shown by disease group for doses above 5 mg/kg/d. There is a dose effect on iron excretion (P < 0.001), with no statistically significant difference in disease groups (P = 0.14). The overall average iron excretion is 0.22, 0.44 and 0.53 mg/kg/d for doses of 10, 20 and 30 mg/kg/d, respectively.
Mentions: Average iron intake per kilogram of body weight varied widely both within and between disease groups (Table 1). On an average, patients with MDS had the lowest transfusional iron intake (0.28 mg/kg/d), while those with DBA had the highest (0.40 mg/kg/d). These differences in transfusional iron intake were also reflected in the proportions of patients having the lowest transfusional iron intake, with 53% of MDS patients, but only 20% of DBA patients requiring <0.3 mg/kg/d. At 20 and 30 mg/kg/d, deferasirox stabilised or reduced mean LIC and serum ferritin levels across a variety of transfusion-dependent anaemias (Table 2). However, changes in LIC were most pronounced in MDS (−9.4 mg Fe/g dw at 30 mg/kg/d) and least pronounced in DBA (−3.2 mg Fe/g dw at 30 mg/kg/d) and paralleled the relative changes in serum ferritin of −1581 and −143 μg/L, respectively. When including dose, iron intake category, disease group and the interaction of iron intake and disease group into an exploratory linear regression model, only dose (P < 0.001) and iron intake category (P < 0.01) had a statistically significant effect on change in LIC (P = 0.15 for disease group, P = 0.61 for interaction term). The same was observed when evaluating iron excretion (mg/kg/d) as the dependent variable, with no difference between disease groups but a statistically significant dose effect (P < 0.001, Fig. 2). Furthermore, iron-chelating efficiency is essentially the same in MDS and other patient groups (Table 2). These results therefore show that in addition to dose, the degree of transfusional iron intake is a key factor governing the outcome of iron chelation therapy across different diseases.

Bottom Line: There were no disease-specific safety/tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases.Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias.There were no disease-specific adverse events.

View Article: PubMed Central - PubMed

Affiliation: University College London, London, UK. j.porter@ucl.ac.uk

ABSTRACT

Objectives/methods: This 1-yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3-81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond-Blackfan anaemia (DBA; n = 30), other rare anaemias (n = 22) or beta-thalassaemia (n = 85). Dosage was determined by baseline liver iron concentration (LIC).

Results: In patients with baseline LIC > or = 7 mg Fe/g dry weight, deferasirox initiated at 20 or 30 mg/kg/d produced statistically significant decreases in LIC (P < 0.001); these decreases were greatest in MDS and least in DBA. As chelation efficiency and iron excretion did not differ significantly between disease groups, the differences in LIC changes are consistent with mean transfusional iron intake (least in MDS: 0.28 +/- 0.14 mg/kg/d; greatest in DBA: 0.4 +/- 0.11 mg/kg/d). Overall, LIC changes were dependent on dose (P < 0.001) and transfusional iron intake (P < 0.01), but not statistically different between disease groups. Changes in serum ferritin and LIC were correlated irrespective of disease group (r = 0.59), supporting the potential use of serum ferritin for monitoring deferasirox therapy. Deferasirox had a safety profile compatible with long-term use. There were no disease-specific safety/tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases.

Conclusions: Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias. There were no disease-specific adverse events. Once differences in transfusional iron intake are accounted for, dose-dependent changes in LIC or serum ferritin are similar in MDS and other disease groups.

Show MeSH
Related in: MedlinePlus