Concomitant Administration of Recombinant Human Erythropoietin (rHuEPO) and Oral Iron Chelator Deferiprone May Stabilize Iron Balance in Transfusion Dependent Patients with Early Myelodysplastic Syndrome (MDS).

Eight transfusion dependent patients with refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) subtypes of MDS (according to the FAB classification) with serum ferritin ranging from 1630 to 4227 μg/l were treated with oral iron chelator deferiprone (Ferriprox, Apotex Ltd., Canada) in a daily dose of 75–80 mg/kg for at least 12 months. Beginning the second month of therapy, rHuEPO (Eprex, Cilag AG, Switzerland or NeoRecormon, Roche Diagnostic, Germany) was administered concomitantly with deferiprone in a dose of 10 000 IU 3 times per week. A significant increase in urinary iron excrection after addition of rHuEPO compared to treatment with deferiprone as a single agent was observed in all patients and the amount of excreted iron ranged from 7.5mg to almost 20mg per day. In one patient with complete response to rHuEPO (Hb > 115 g/l + transfusion independence) and in another patient with partial response resulting in transfusion independence, serum ferritin level decreased from 3034 to 1872 μg/l and from 2086 to 879 μg/l, respectively. The results corresponded with a moderate decrease in liver iron documented by NMR imaging. In 6 patients who did not respond to rHuEPO and remained transfusion dependent a simultaneous administration of rHuEPO and deferiprone enabled to stablize serum ferritin level despite continuing iron load from transfusions. The treatment was well tolerated except one patient, in whom adverse GIT symptoms led to cessation of deferiprone administration after 4 months of treatment. The ability of deferiprone to bind intracellular iron that may be either excreted from the body or donated to partially saturated transferrin for utilization in bone marrow for rHuEPO stimulated erythropoiesis on one hand and an increased excretion of deferiprone chelated non transferrin bound iron originating from an increased amount of destroyed red blood cells on the other hand may be a possible explanation of observed phenomenon. A concomitant administration of rHuEPO and deferiprone might be an effective tool for maintaining iron balance in transfusion dependent iron overloaded patients with early MDS who are not indicated for intensive treatment.