LONG-TERM TREATMENT OF TRANSFUSIONAL IRON OVERLOAD WITH THE ORAL IRONCHELATOR DEFERIPRONE (L1) - A DUTCH MULTICENTER TRIAL

We performed an open, nonrandomized, multicenter phase-II trial to eva luate the efficacy and toxicity of 1 year of treatment with the oral i ron chelator deferiprone in 38 mainly nonthalassemic patients with tra nsfusional iron overload. Initial serum ferritin varied between 996 an d 11.644 mu g/l. Patients were treated with 3-6 g of deferiprone daily . Mean urinary iron excretion (UIE) in 36 evaluable patients was 21.0 mg/24 h and was significantly higher in the patients with thalassemia than in those with myelodysplasia. Negative iron balance was achieved in 20 patients (56%). The median duration of treatment was 10 months; due to side effects and other causes only 20 patients completed 1 year of treatment. Mean serum ferritin levels decreased from 3563 mu g/l a t the start of the trial to 2767 mu g/l at 6 months (26 patients, p<0. 004) and to 2186 mu g/l at 12 months (20 patients, p<0.005). Serum fer ritin levels normalized in two patients who were no longer transfusion dependent. Deferiprone was clearly not effective in three patients (t wo with myelofibrosis, one with myelodysplasia). One patient with myel odysplasia developed agranulocytosis after 12 months of treatment; thi s was rapidly reversible after stopping deferiprone. Three patients ha d a mild and transient decrease in white blood cell count. Other side effects leading to withdrawal from the trial consisted mainly of nause a (3 patients), arthralgia (2), and skin rash (1). No clinical signs o f zinc deficiency were seen, although zinc excretion was increased in three patients. No changes were seen in liver enzymes, creatinine, ant inuclear factor, T-cell subsets, cardiac function, visual acuity, and audiogram. Although our results confirm deferiprone as an effective ir on chelator in patients with thalassemia and in some patients with oth er forms of iron overload, there is still some concern about the safet y of this drug, which therefore, at this time, should be used exclusiv ely in well-controlled clinical trials.