Deferiprone Oral Solution, An Alternative for Early Chelation Therapy In Young Children with Transfusional Iron Overload: A Preliminary Data From A 6-Month Study Period

The choice of chelation therapy is limited in young children with transfusional iron overload. Desferrioxamine can disturb bone growth especially in those younger than 6 years of age. Moreover, incooperation of young patients to subcutaneous overnight infusion of the medication causes none adherence. Deferasirox is an unaffordable chelation for many patients in developing countries. Deferiprone has been evaluated in several studies for its safety and efficacy in young children. However, the widely used large tablet form of deferiprone may not be suitable for this group of patients. Objective: To study efficacy, safety and tolerability of deferiprone oral solution for early chelation therapy in young children with transfusional iron overload. Inclusion criteria: Patients age <10 years with transfusional iron overload (ferritin >1,000 ng/mL or received >10 transfusions) at Pediatrics Department, Faculty of Medicine, Ramathibodi Hospital, Mahidol University that fail to accomplish adequate chelation by desferrioxamine or deferiprone tablet due to poor compliance. Methods: Deferiprone oral solution (Ferriprox^®) was given at a dose of 75 mg/kg/day in three divided dose for patients who previously received tablet form of deferiprone and 50 mg/kg/day for others who never experienced deferiprone. Ferritin level, complete blood counts, alanine transferase, serum creatinine and spot urine protein were measured every 4 weeks. Complete history taking and physical examination were performed and compliance was recorded during monthly visit. Results: A total of 10 patients were enrolled with equal male and female. The median age was 4.8 years (range 2–9.8 years) whereas seven patients was ≤5 years of age. Seven out of 10 patients were diagnosed β thalassemia HbE disease and the rest were diagnosed β thalassemia major, HbH disease and hereditary spherocytosis respectively. Only one patient was splenectomized and none of them was seropositive for hepatitis B or C virus. All patients have received regular packed red cell transfusion for the median of 3.9 years (range 1.1–6.4 years) to maintain pretransfusion hematocrit of 27%. The median transfusional iron load was 0.39 mg/kg/day (range 0.29–0.48 mg/kg/day) whereas the median ferritin level at the beginning of the study was 1,598.2 ng/mL (range 654.4–3, 163.8 ng/mL). Two patients were previously chelated with desferrioxamine, three patients with deferiprone tablet and 1 with combined desferrioxamine and deferiprone tablet. The remaining four patients were naïve for deferiprone oral solution.

Efficacy The median ferritin level at the end of 6 months was significantly lower than that of pretreatment period (median 1,445.8 ng/mL, range 114.6–2806.2 ng/mL, p=0.037). Four out of 10 patients had final ferritin level at 6 months <1,000 ng/mL and half of them had ferritin level <500 ng/mL. This group of four patients were ≤5 years old and had ferritin level between 654.4–1, 507.8 ng/mL at the beginning of study. However, the transfusional iron load was ranging from 0.36–0.48 mg/kg/day. They all received 50 mg/kg/day of deferiprone solution. One out of these four was a patient with HbH disease who was occasionally transfused. The ferritin level of the boy decreased from 654.4 ng/mL to 114.6 ng/mL and deferiprone oral solution could be stopped at the end of the third month.

Safety No episode of neutropenia or agranulocytosis occurred. One patient had an episode of mild thrombocytopenia of 137,000/μL during the second month of treatment. However, deferiprone oral solution was continued and spontaneous recovery of platelet counts was observed on the following month. No transaminitis and renal impairment were found. Neither arthralgia nor GI discomfort occurred.

Tolerability All patients tolerated well with deferiprone oral solution and excellent compliance of the treatment was achieved.

Deferiprone oral solution is a safe and effective alternative for chelation therapy in transfusion-related iron overload especially those with younger age. Serum ferritin level decreased well in a short period of time with only as low dose of deferiprone as 50 mg/kg/day when given at earlier age with starting ferritin level ≤1,000 ng/mL. Better absorption of deferiprone in the form of solution may be a reason for such efficacy. Moreover, liquid formulation of the medication could be a solution to improve adherence to chelation treatment in young children.

No relevant conflicts of interest to declare.