BACKGROUND AND OBJECTIVE: Deferiprone (L1) is a largely studied oral chelator in clinical setting, however, no definite conclusions concerning efficacy and toxicity still could be drawn. In an ongoing prospective trial with L1, we evaluated the efficacy and tolerance-toxicity in patients with thalassemia major previously treated by desferrioxamine (DFO); the specific aim of the study is to demonstrate that L1 could be an alternative to DFO in some patients with an acceptable toxicity. DESIGN AND METHODS: Sixty-nine patients over 13 years of age with poor compliance to DFO were considered for the study. The design included a liver biopsy before starting L1 in all patients in order to define liver siderosis either by histologic grading or by hepatic iron concentration (HIC); only patients with a minimum HIC of 4 mg/g dry weight entered the study. A repetition of the liver biopsy after one year of L1 was planned; further evaluations included serum ferritin, plasma iron, transferrin TIBC and iron urine excretion. L1 was given at 70 mg/kg/day in three divided doses. Toxicity was monitored either clinically or by controlling liver, kidney and marrow function by specific tests. Concerning clinical characteristics 52 patients showed hypogonadism (78%), 39 growth retardation (58%), 6 diabetes (9%), 4 cardiomyopathy (6%), 9 hypothyroidism (12%); 45 patients had chronic liver damage (65%). RESULTS: We focus this report on data collected in a group of 29 patients with a minimum follow-up of one year (14-33 months). The mean ferritin value was 3748 ng/mL (range: 200-10,000) and 2550 ng/mL (range: 80-14,500), before and while on L1 therapy, respectively (p = 0.001); the mean sideruria changed from 17.25 mg/dL (range: 5.4-50) to 20.98 mg/dL (range: 10-40), on DFO and L1, respectively (p = 0.078); the ratio between plasma iron (sideremia) and transferrin TIBC changed from 0.96 with DFO to 0.86 with L1 (0.014). A correlation with grade of liver siderosis and serum ferritin (p = 0.069) and iron urine excretion (p = 0.008) was recorded. The judgement of efficacy showed that L1 was effective (EF) in 9 patients, no assessable (UN) in 11 patients, not effective (NE) in 2 patients and with no advantages with respect to DFO in 7 patients. Liver biopsy was repeated in 20 patients showing a reduction of grade of liver siderosis and iron content in 7 patients. Clinical toxic effects of L1 were gastric intolerance (one patient), joint pain (three patients) and mild and temporary neutropenia (one patient). INTERPRETATION AND CONCLUSIONS: This preliminary experience shows that L1 is effective in several patients with thalassemia with poor compliance to DFO and to improve iron burden and iron excretion with generally minor side effects. L1 could be an alternative to DFO in some patients, however the recognition of neutropenia warrants a careful evaluation of patients and efforts finalized to early recognition of those to be addressed with this new and still experimental therapy.
BACKGROUND AND OBJECTIVE:Deferiprone (L1) is a largely studied oral chelator in clinical setting, however, no definite conclusions concerning efficacy and toxicity still could be drawn. In an ongoing prospective trial with L1, we evaluated the efficacy and tolerance-toxicity in patients with thalassemia major previously treated by desferrioxamine (DFO); the specific aim of the study is to demonstrate that L1 could be an alternative to DFO in some patients with an acceptable toxicity. DESIGN AND METHODS: Sixty-nine patients over 13 years of age with poor compliance to DFO were considered for the study. The design included a liver biopsy before starting L1 in all patients in order to define liver siderosis either by histologic grading or by hepatic iron concentration (HIC); only patients with a minimum HIC of 4 mg/g dry weight entered the study. A repetition of the liver biopsy after one year of L1 was planned; further evaluations included serum ferritin, plasma iron, transferrinTIBC and iron urine excretion. L1 was given at 70 mg/kg/day in three divided doses. Toxicity was monitored either clinically or by controlling liver, kidney and marrow function by specific tests. Concerning clinical characteristics 52 patients showed hypogonadism (78%), 39 growth retardation (58%), 6 diabetes (9%), 4 cardiomyopathy (6%), 9 hypothyroidism (12%); 45 patients had chronic liver damage (65%). RESULTS: We focus this report on data collected in a group of 29 patients with a minimum follow-up of one year (14-33 months). The mean ferritin value was 3748 ng/mL (range: 200-10,000) and 2550 ng/mL (range: 80-14,500), before and while on L1 therapy, respectively (p = 0.001); the mean sideruria changed from 17.25 mg/dL (range: 5.4-50) to 20.98 mg/dL (range: 10-40), on DFO and L1, respectively (p = 0.078); the ratio between plasma iron (sideremia) and transferrinTIBC changed from 0.96 with DFO to 0.86 with L1 (0.014). A correlation with grade of liver siderosis and serum ferritin (p = 0.069) and iron urine excretion (p = 0.008) was recorded. The judgement of efficacy showed that L1 was effective (EF) in 9 patients, no assessable (UN) in 11 patients, not effective (NE) in 2 patients and with no advantages with respect to DFO in 7 patients. Liver biopsy was repeated in 20 patients showing a reduction of grade of liver siderosis and iron content in 7 patients. Clinical toxic effects of L1 were gastric intolerance (one patient), joint pain (three patients) and mild and temporary neutropenia (one patient). INTERPRETATION AND CONCLUSIONS: This preliminary experience shows that L1 is effective in several patients with thalassemia with poor compliance to DFO and to improve iron burden and iron excretion with generally minor side effects. L1 could be an alternative to DFO in some patients, however the recognition of neutropenia warrants a careful evaluation of patients and efforts finalized to early recognition of those to be addressed with this new and still experimental therapy.