Efficacy and Side Effects of Deferiprone in Children with Iron Overload.

Background: Complications due to tissue iron overload are the major cause of morbidity and mortality in patients on long-term transfusion. Desferrioxamine was the only available chelator for treatment until 1999, when Deferiprone (L1) was licensed for use. L1 is an orally active drug unlike desferrioxamine, which can only be used either intravenously or subcutaneously.

Aim: The aim of this study was to assess the efficacy and safety of this drug for treatment of children with iron overload.

Method: Retrospective analysis of case notes of children on L1 for at least one year duration. Children were on long-term transfusion for transfusion dependent anaemias including thalassaemia major, thalassaemia intermedia and sickle cell anaemia. The main indication for starting L1 was inefficient control of iron overload despite subcutaneous desferrioxamine. L1 was started at a dose of 75 mg/kg bodyweight. Liver biopsy was performed to assess histology and liver iron content prior to starting L1. All patients underwent echocardiogram to assess cardiac status prior to starting L1. The average ferritin levels were recorded for the year before and the year after starting L1.

Results: 13 patients met the inclusion criteria. The median age for commencing transfusion was 1.96 years (range 0.16 – 10.83). Desferrioxamine was started a median of 1.25 years after starting transfusion and patients were on desferrioxamine for a median duration of 9 years (range 1.16 – 14.58) before starting L1. 11 patients had liver biopsy prior to starting L1 and 3 had liver biopsy post L1. Wilcoxon Signed Rank Test was used for statistical analysis.

The results are tabulated as follows:

Pre L1

Post L1

p value

Mean Ferritin (microgm/lt)

2359 (1275–4157)

1801 (644–3103)

0.002

Mean Desferal dose/week

10.2 gm

6.78 gm

0.009

Mean Desferal duration/week

61.3 hours

44 hours

0.009

Liver Biopsy: The mean liver iron content in the three patients who underwent liver biopsy one year post L1 dropped from 1469 microgm/100mg dry liver to 325.3microgm/100mg dry liver. Histologically one patient showed an improvement in siderosis, the other in fibrosis and the third patient had no change in histology.

Side effects: Three patients developed side effects. One patient had arthralgia and zinc deficiency. One had only arthralgia and the other developed neutropenia 8 months post L1 and hence L1 was discontinued. The patient recovered with GCSF and subsequently had no neutropenia. Arthralgia in these two patients improved with analgesics and they continued on L1.

Summary: In this group of paediatric patients L1 has been shown to be effective in reducing iron overload as evidenced by a reduction in mean serum ferritin levels and desferrioxamine requirements. L1 also resulted in a fall in liver iron content and improvement in histology in patients who have undergone liver biopsy a year after being on L1. L1 was well tolerated in all patients with only one patient developing neutropenia which was reversible.

In conclusion, deferiprone appears to be a safe and effective drug for treating iron overload in children, and it may allow reduction in the dose and frequency of desferrioxamine use.