Search

A 36-year-old transfusion-dependent thalassemia major patient presented with febrile neutropenia and anemia. Deferiprone (L1) was discontinued as it was suspected to be the offending agent and prompt broad-spectrum antibiotic therapy was initiated after which the patient improved. After 11 days the patient developed hemorrhagic stroke and seizure whereby aspirin was discontinued and supportive therapy was given. Agranulocytosis is the most serious complication reported with L1 but, to the best of our knowledge, there are no previous reports on hemorrhagic stroke associated with the use of the agent, and hence, the etiology of the stroke which followed agranulocytosis caused by L1 remains obscure.

Deferiprone at a dose of 75 mg/kg/day is not sufficiently effective to maintain iron stores at a level which has been considered safe in all patients with iron overload. Our main aim was to determine the safety of long-term therapy with high-dose (100 mg/kg/day) deferiprone. A secondary aim was to determine the efficacy of this high dose. Twelve thalassemia major patients received deferiprone at a dose of 100 mg/kg/day over 2 years. Transient aspartate aminotransferase increase (8 patients), gastrointestinal discomfort (3 patients) and arthralgia (2 patients) were the most commonly reported side effects. None of the patients discontinued therapy. The mean serum ferritin level fell from 3,901 +/- 3,618 to 1,790 +/- 2,205 microg/l after 2 years (p < 0.05). Five of the 12 patients continued to receive deferiprone for an additional 3 years. No new side effects were encountered. The mean serum ferritin level in this subgroup was initially 2,510 +/- 332 microg/l and dropped to 1,511 +/- 664 microg/l after 5 years (p < 0.05). Liver iron levels at the end of the 2-year study ranged from 1.0 to 30.9 mg/g dry weight, 3 of the patients having levels above 15 mg/g., ((c) 2005 S. Karger AG, Basel)

Twelve thalassaemia major patients have been given deferiprone 75 mg/kg body weight daily as iron chelation therapy for 5 years. Their ages ranged from 18 to 34 years (mean 24.2) at the end of the study. Two patients were hepatitis C virus (HCV) mRNA positive and a further 5 were positive for HCV antibody. The mean serum ferritin level fell significantly from 4,302 +/- 2,245 microg/l SD at baseline to 3,032 +/- 1,155 microg/l at 2 years (p = 0.037) and 2,229 +/- 1,070 microg/l (p = 0.007) at 5 years. At the end of the study, liver iron ranged from 3.59 to 23.7 mg/g dry weight (mean 11.9 +/- 5.4), 3 patients having levels >15 mg/g. There was no significant change in serum AST levels, but ALT levels fell significantly at 2 years (p = 0.019) and 5 years (p = 0.001). Liver biopsy at the end of the study showed no evidence of hepatic fibrosis caused by deferiprone. Cardiac studies showed no overall change in left ventricular ejection fraction but a significant improvement in isovolumic relaxation time (p = 0.045). We conclude that in this albeit small group of thalassaemia major patients, deferiprone was a safe long-term method of iron chelation. In a minority, higher doses of deferiprone or a combination with desferrioxamine would be needed to lower liver iron below 15 mg/g., (2004 S. Karger AG, Basel.)

Desferrioxamine (DFX) alone (40-50 mg/kg/d s.c. over 8-12 h, five times weekly) was compared with combined DFX twice weekly and deferiprone (75 mg/kg/d) over 12 months in previously poorly chelated thalassaemia patients. Serum ferritin fell from 5506 +/- 635 microg/l (mean +/- SEM) to 3998 +/- 604 microg/l (P < 0.001; n = 14) in the DFX group and from 4153 +/- 517 microg/l to 2805 +/- 327 microg/l in the combined group (P < 0.01; n = 11). Deferiprone plus DFX produced a greater mean urine iron excretion (1.01 mg/kg/24 h) than iron intake from blood transfusion in each patient. Main side-effects were skin reactions (DFX alone), nausea and arthralgia (combined therapy). As chelation therapy, the combined protocol was as effective as DFX five times weekly.

Beta-thalassemia requires life-long treatment, including regular blood transfusion and daily iron chelation by desferrioxamine, which places considerable burden on the social and psychological life of patients. It is expected that oral chelation therapy, which is easier to administer, would improve their psychosocial status. In this sutdy, interviews were conducted with a series of 44 patients recently placed on oral chelation therapy to evaluate their reactions to the new treatment. Eighty-six per cent of patients complied better with the oral chelation therapy. Fifty per cent of patients mentioned that relief from the desferrioxamine pump was the major improvement, while 47% felt psychologically better. Fifty per cent of patients noted improvements in their relationships, while 63% noted increased social activities. Evaluation of a larger sample of patients over a longer period of time is needed in order to confirm the favourable results obtained in this study.

Introduction: Iron-chelating therapy with deferoxamine in patients with thalassemia major has dramatically improved the prognosis of this disease. However, the limitations of this treatment have stimulated the design of alternative orally active iron chelators., Objective: To compare the effectiveness and safety of, and compliance with, oral deferiprone (L1), and deferoxamine, in thalassemia major patients., Methods: All patients were followed up in one center in Lebanon. Sixteen patients were on L1 (75 mg/kg/d), and 40 patients on subcutaneous deferoxamine (20-50 mg/kg/d). Serum ferritin level, urinary iron excretion (UIE) and side effects were monitored over a two year period., Results: Patients on L1 had an initial serum ferritin concentration of 3663+/-566 microg/l (mean+/-SEM), that dropped to 2599+/-314 at 6 months (p<0.02; paired t-test), and stabilised at that level over the 24 months follow up. Patients on deferoxamine had an initial mean serum ferritin concentration of 3480+/-417 (NS compared to the L1 group), which dropped gradually to 3143+/-417 (p<0.05) and 2819+/-292 (p<0.02) at 6 and 24 months, respectively. The most common adverse reactions associated with L1 were arthralgia and nausea, but they did not necessitate stopping the drug., Conclusion: L1 had comparable efficacy as deferoxamine with minimal side effects and better compliance. Provided long term side effects are not encountered, L1 seems to be a valuable alternative iron chelator for patients unable or unwilling to use deferoxamine effectively.

We report our experience with deferiprone (L1) (DFP) in 17 thalassemic patients, followed up in one center in Lebanon, who were initially on desferrioxamine and then shifted to DFP at a dose of 50-75 mg/kg/day as the sole chelator during 1-year follow-up. All 17 patients were compliant with therapy and there was no change in physical examination over the study period. Eight patients (47.1%) were positive for hepatitis C virus (HCV) antibodies. Urinary iron excretion was 21.8 +/- 14 mg/24 h (mean +/- SD) 1 week after starting DFP and dropped 12 months later to 13 +/- 7.4 mg/24 h (p = 0.009, paired t test). The initial serum ferritin level was 3,863 +/- 2,344 microg/l which dropped to 3,179 +/- 2,075 at 12 months after starting therapy (p = 0.07). HCV-negative patients as a group exhibited a significant decrease in serum ferritin after 6 and 12 months of DFP therapy (3,942 +/- 2,739 vs. 2,341 +/- 1,179 and 2,681 +/- 1,519 microg/l; p < 0.03 and p < 0.05, respectively). The most frequent side effects were joint pain, stiffness or swelling in 6 patients (35.3%), and nausea in 7 patients (41.2%), but these were well tolerated and did not require stopping treatment.