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Title: Management of Iron Overload in Patients With Sickle Cell Disease

"Management of Iron Overload in Patients With Sickle Cell Disease"

By Bruce Wilson PENNSYLVANIA, PA -- September 12, 2006 -- Chelation therapy is an effective treatment modality to reduce iron overload and prevent tissue damage in patients with sickle cell disease (SCD), according to an expert speaking at a recent sickle cell disease meeting. John B. Porter, MA, MD, professor of hematology and consultant hematologist, University College, London, United Kingdom, said the goals of chelation treatment are to maintain safe levels of iron, first by preventing iron from reaching toxic levels, and secondly to remove excess iron when it has already occurred. Iron overload is practically inevitable in SCD patients receiving repeated transfusions and occurs especially rapidly in the liver. High rates of liver iron (> 15 mg/g dry weight) have been associated with cardiac death in patients with thalassemia (Brittenham et al. [N Engl J Med 1994;331:567-573).

"With exchange transfusions, the rate of [iron] loading can be decreased, but the ways in which exchange transfusions are done differ enormously from center to center and the net unloading differs from center to center," Dr. Porter said during his presentation.

Therefore, the rationale of chelation therapy for SCD patients is clear. "Although there is inadequate prospective data, the risk of liver loading and damage [in SCD patients] is similar to thalassemia major. Data on cardiac loading is incomplete, but we should still aim to control liver iron concentration to minimize fibrosis, cirrhosis, and hepatocellular carcinoma, and to decrease the likely late risk of damage to other tissues," he told delegates.

The 3 available chelators for treating iron overload have different densities -- ie, the number of bonds they form with elemental iron. These are deferipone (bidentate), deferasirox (tridentate), and deferoxamine (hexadentate).

Deferoxamine has been available for more than 3 decades and must be administered intravenously. Deferipone is indicated for iron overload in patients with thalassemia major who do not respond to deferoxamine or in patients for whom it is contraindicated.

Studies show that deferipone may be less effective than deferoxamine in reducing liver iron concentrations, but deferipone may have a cardioprotective effect.

Deferasirox has shown high therapeutic efficacy in animal studies. It is given as a once-daily dispersible tablet.

A study presented at the 2005 American Society of Hematology (ASH) meeting showed that deferasirox at a daily dose of 20 mg/kg reduces labile plasma iron after a single dose and peak labile plasma iron after multiple dosing in patients with beta-thalassemia (Daar et al. Blood 2005;106:abst. 2697).

In another study reported at last year's ASH, deferasirox consistently reduced liver iron concentrations and serum ferritin levels in patients with transfusion dependent anemia, including beta-thalassemia, Diamond-Black anemia, myelodysplastic syndromes, and other anemias (Greenberg et al. Blood 2005;106:abst. 2694). A third study at the meeting demonstrated that deferoxamine effectively removed cardiac iron by 20.5% and liver iron by 51% in iron-loaded gerbils (Wood et al. Blood 2005;106:abst. 2695).

In a study by Dr. Porter and colleagues, deferasirox demonstrated approximately twice the chelation efficiency as deferoxamine in patients with transfusional hemosiderosis (Porter et al. Blood 2005;106:abst. 2690) "This is encouraging and we need to do further studies on this," Dr. Porter said.

[Presentation title: Management of Iron Overload.]

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