Pediatric Clinics of North America - CIPERJ

470 KWIATKOWSKI
biopsy or SQUID decreased from 15 to 8.7 mg/g dry weight after an average
of 3.1 years of treatment [30]. Eight of 10 patients who had initial liver iron
concentrations associated with a high risk for cardiotoxicity (O15 mg/g dry
weight) had levels that fell to below that threshold with deferiprone treatment,
and no patient who had lower initial hepatic iron concentrations
rose above this threshold. With longer follow-up of a mean of 4.6 years in
18 patients, although there was an overall reduction in liver iron concentration
from baseline (16.5 to 12.1 mg/g dry weight, P ¼ .07), in seven patients,
the liver iron concentration remained above 15 mg/g liver dry weight [65].In
another report of 20 patients who received deferiprone (70 mg/kg daily) for
1 year or more, the mean liver iron content increased from 16 to 21 mg/g dry
weight, although this change did not reach statistical significance [64]. Liver
iron content decreased in seven patients, rose in 12 patients, and remained
the same in one patient. Thus, the data suggest that chelation with deferiprone
(at a dose of 75 mg/kg per day) does not reduce liver iron concentration
effectively in some patients.
Few randomized clinical trials have compared the efficacy of deferiprone
directly to deferoxamine for the treatment of iron overload. In one study of
144 patients randomized to receive deferiprone (75 mg/kg per day) or deferoxamine
(50 mg/kg per day), the reduction in serum ferritin levels after 1
year was similar between the two treatment groups [57]. In a subset of 36 patients
who underwent liver biopsy at the beginning and end of treatment, the
mean reduction in liver iron content also was not significantly different
between the two groups. In a more recent study, 61 Italian and Greek
patients were randomized to receive deferoxamine (50 mg/kg daily for
5 days a week) or deferiprone (75 mg/kg per day initially, increasing to
100 mg/kg per day) [66]. The changes over a 1-year period in serum ferritin
level and liver iron content assessed by SQUID did not differ significantly
between the two treatment groups. In contrast, in a third study, in which
30 children were randomized into three groups to receive deferoxamine
(40 mg/kg per day, 5 days per week), deferiprone (75 mg/kg daily), or combination
treatment with deferiprone (75 mg/kg daily) and deferoxamine
(40 mg/kg per day, twice weekly), after 6 months of treatment, those receiving
deferoxamine alone had a significant reduction in serum ferritin, whereas
the other two groups had a slight rise in ferritin levels [67].
The lack of reduction in serum ferritin or liver iron concentration in
some patients receiving deferiprone may be explained by a variety of reasons,
including poor compliance, variability in drug metabolism rate, or
higher transfusional iron burden. The latter two problems potentially
might be overcome by treating with a higher dosage of deferiprone. In
one study, increasing the daily dose of deferiprone (from 75 mg/kg to
83 to 100 mg/kg) resulted in a fall in serum ferritin level in nine patients
who had had inadequate chelation at the lower dose [55]. Although no
significant increased toxicity has been found in small studies using higher
doses of deferiprone (up to 100 mg/kg daily) [66,68], larger studies are