Source: DGNews  |  Posted 4 years ago

By John Gever

ATLANTA, GA -- December 13, 2007 -- Complications of beta thalassemia such as death and cardiac dysfunction declined dramatically when deferiprone was added to deferoxamine iron chelation treatment, according to a new single-institution study.

The results were presented here on December 10 at the 49th American Society of Hematology (ASH) Annual Meeting and Exposition by Kallistheni Farmaki, MD, Director, Blood and Thalassemia Service, General Hospital of Corinth, Corinth, Greece.

The combination was individually tailored and included 40 to 60 mg/kg deferoxamine given by infusion 3 to 6 days/week and 75 to 100 mg/kg/day oral deferiprone.

"Combined deferoxamine and deferiprone therapy has been associated with increased survival, reduced incidence of cardiac disease, and reversal of pre-existing cardiac dysfunction," Dr. Farmaki said.

From 1990 to 2000, when beta thalassemia patients only received deferoxamine monotherapy, 11 patients died. Between 39 and 50 patients were at risk each year.

From 2001 to 2007, with 51 to 56 patients at risk annually, no patients died, Dr. Farmaki reported.

The researchers also studied the effects on 50 patients who switched from deferoxamine monotherapy to the combination regimen. Various parameters associated with common complications of beta thalassemia were measured at baseline and after 5 to 6 years of treatment.

Serum ferritin levels, the usual laboratory measure for iron chelation, declined from 3,421 mcg/L at baseline to 87 mcg/L. Cardiac function improved as well. In 12 patients with cardiac abnormalities disease at baseline, mean left ventricular ejection fraction (LVEF) increased to 67.6% from 54.2% at baseline.

Patients with normal cardiac function at baseline also showed increased LVEF, to 72.1% from a baseline level of 63.8%.

Glucose metabolism normalized in many patients. Among 16 with impaired glucose tolerance at baseline, 10 showed normal levels when tested after 5 to 6 years of combination therapy. All six patients with insulin-dependent diabetes at baseline reduced their daily insulin requirements, Dr. Farmaki said.

Among 17 patients requiring thyroxin supplementation at baseline, seven were able to discontinue and another four reduced their dosages.

Normal sex steroid function was restored in many patients as well. Testosterone levels increased in male patients and four of 19 women with secondary amenorrhea had fertility restored, as evidenced by pregnancy.

Adverse effects were not common and were generally mild. Dr. Farmaki said no cases of agranulocytosis occurred.

One drawback of the combined therapy may have been decreased patient compliance with treatment. Dr. Farmaki said that 10% of patients failed to comply with the combination regimen, even though dosing could be adjusted to individual patients' needs.

[Presentation title: Reversal of Complications Following Intensive Combined Chelation in Beta thalassemia Major Patients. Abstract LB4]