Study of Deferiprone or Deferoxamine Versus Combination Therapy in Iron-Loaded Thalassemia Patients in Taiwan.

BACKGROUND: Deferiprone (L1) has been suggested to be an effective oral chelation therapy for regular transfusion thalassemia major patients. The purpose of this study was to test the efficacy either of L1 or DFO alone, or combination use, and also monitor the safety of L1 in Taiwan.

MATERIALS AND METHODS: From April 1999 to December 2005, 114 thalassemic patients from 5 treatment centers were enrolled in this program. L1 at the standard dose of 75mg/kg was given to 57 patients. The mean administered dose of L1 was 72.5mg/kg body weight divided into three doses per day. DFO at the standard dose of 30–50mg/kg/day at least 5 days/week was given to 26 patients, and the mean DFO dose was 46.5mg/kg/day 5 or more days/week. Combined therapy of daily L1 with subcutaneous DFO was given 2 to 6 days each week to the other 31 patients. The mean administered dose of DFO was 45.7mg/kg body weight 2 to 6 days per week, and the mean L1 dose was 71.5mg/kg/day divided into 3 doses per day. The therapeutic efficacy and potential side effects on cardiac and/or hepatic systems of these patients were assessed by left ventricular ejection fraction, T2-weighted magnetic resonance imaging (T2-MRI) and biochemical parameters and liver biopsies.

RESULTS: No significant liver function impairment, neutropenia or arthropathy ever occurred. Only one patient was found to have transient leukopenia (he had a coincidental viral infection at that time). Three patients had temporary G-I upset but no one required discontinuation of L1. The serum ferritin level was significantly lower in 9 patients receiving L1 for more than 6 years (p=0.04), 22 patients receiving L1 for 2–3 years (p<0.01) and 31 receiving the combined therapy (p=0.01), yet significantly higher in those receiving DFO only (p<0.01). The combined therapy group witnessed a more significant ferritin decrease than the L1 alone or DFO alone groups and hepatic function improved or stabilized notably. Besides a decrease of iron, no marked pathohistological changes were observed in the liver biopsies. GPT had a decreasing trend in 3 subgroups of L1 & combination therapy group, however there was no statistic significance. Cardiac studies showed a marked recovery of signal intensity in the heart T2-MRI and increased LVEF, indicating a significant reduction of iron load in the heart in L1 use and in over 50 -month combination therapy groups

CONCLUSIONS: We conclude that in this large group of thalassemia major patients, L1 was a safe long-term method of iron chelation. Combining subcutaneous DFO with L1 therapy is an improved method not only for patients inadequately chelated but also by lowering the DFO dosage to less than 25%. This study also shows that the combined therapy is associated with an improvement in heart function.