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Deferasirox reduces iron overload markers in myelodysplastic syndrome

NEW YORK (Reuters Health) – Deferasirox reduces serum ferritin and labile plasma iron in patients with myelodysplastic syndrome (MDS), according to a report online April 30th in the Journal of Clinical Oncology.

High transfusion requirements in patients with MDS place them at high risk for iron overload. Iron chelators like deferoxamine have been shown to improve hematologic parameters in several case reports and small studies.

The new report, from Dr. Alan F. List from H. Lee Moffitt Cancer Center, Tampa, Florida and colleagues, involved 173 patients with low- or intermediate-risk MDS who received deferasirox.

Over a three-year period, more than three quarters of the patients (138, 79.7%) discontinued deferasirox for reasons ranging from adverse events (43 patients) and death (28 patients) to administrative problems (27 patients) and nonenrollment in the extension phase of the study (12 patients).

Despite average transfusion requirements of four units of red blood cells per month, the median serum ferritin fell by 23.2% in the 91 patients who completed a year of treatment, by 36.7% in the 49 patients who completed two years, and by 36.5% in the 33 patients who completed year three.

Labile plasma iron concentrations normalized by week 25 and remained normal for the remainder of the study in 47 patients who had elevated baseline levels.

Median transferrin saturation decreased from a baseline level of 91% to 67% at the end of the study.

Improvements in serum ferritin were associated with declines in hepatic transaminase levels, and hematologic measures of MDS improved in 15% (erythroid or neutrophil responses) to 22% (platelet responses) of patients.

Improvements in labile plasma iron did not differ significantly between hematologic responders and nonresponders, although there was a trend toward improved overall survival in responders compared with nonresponders.

Adverse events that led to discontinuation of deferasirox in at least 3% of patients included progression to acute myeloid leukemia, GI disorders, general disorders and administration site conditions, infections, and nervous system disorders. None of the 28 deaths were considered to be related to the study drug.

“Overall, this study demonstrated improvements in iron parameters with prolonged deferasirox in a cohort of heavily transfused lower risk patients with MDS accompanied by improvements in hepatic transaminases and hematologic improvement,” the researchers conclude.

“A randomized controlled trial is warranted to better ascertain the clinical impact of deferasirox therapy in lower risk patients with MDS,” they add.

Deferasirox is FDA approved for the treatment of chronic iron overload due to blood transfusions in patients two years of age and older. It is not specifically approved for patients with MDS or other hematologic disorders.


J Clin Oncol 2012.