Deferasirox administration for the treatment of non-transfusional iron overload in patients with thalassaemia intermedia.

Abnormal iron regulation in patients with thalassaemia intermedia may lead to iron overload even in the absence of transfusions. There are limited data on iron chelator use in patients with thalassaemia intermedia and no guidelines exist for the management of iron overload. We present data from 11 patients with thalassaemia intermedia treated with deferasirox (Exjade(®) , 10-20 mg/kg/d) for 24 months. Liver iron concentration and serum ferritin levels significantly decreased over the first 12 months (P = 0·005) and continued to decrease over the remainder of the study (P = 0·005). This small-scale study indicated that deferasirox may be suitable for controlling iron levels in patients with thalassaemia intermedia.

The pancreas in beta-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbances.

The study aims at describing the MR features of pancreas in beta-thalassemia major, investigating the relations between MR findings and glucose disturbances and between hepatic and pancreatic siderosis. Signal intensity ratios of the pancreas and liver to right paraspinous muscle (P/M, L/M) were retrospectively assessed on abdominal MR imaging studies of 31 transfusion-dependent patients with beta-thalassemia major undergoing quantification of hepatic siderosis and 10 healthy controls, using T1- (120/4/90), intermediate in and out of phase - (120/2.7, 4/20), and T2*-(120/15/20) weighted GRE sequences. Using the signal drop of the liver and pancreas on opposed phase images, we recorded serum ferritin and results of oral glucose tolerance test (OGTT). Decreased L/M and P/M on at least the T2* sequence were noticed in 31/31 and 30/31 patients, respectively, but no correlation between P/M and L/M was found. Patients with pathologic OGTT displayed a higher degree of hepatic siderosis (p < 0.04) and signal drop of pancreas on opposed phase imaging (p < 0.025), implying fatty replacement of pancreas. P/M was neither correlated with glucose disturbances nor serum ferritin. Iron deposition in the pancreas cannot be predicted by the degree of hepatic siderosis in beta-thalassemia major. Fatty replacement of the pancreas is common and may be associated with glucose disturbances.

Iron chelation treatment with combined therapy with deferiprone and deferioxamine: a 12-month trial.

The simultaneous use of deferioxamine (DFO) and deferiprone (DFP) has an additive effect in iron excretion in transfusion-dependent thalassemic patients. In a prospective study, we evaluated the safety and effectiveness of combined therapy with these two chelators. Fifty patients with beta-thalassemia were uniformly treated with DFP for 4 days per week and combined therapy with DFP and DFO for 3 days of the week. Efficacy was evaluated by ferritin and cardiac shortening fraction (SF). Hepatic hemosiderosis was also assessed by estimation of the T2 relaxation time by magnetic resonance in a subgroup of patients. Forty-three patients completed 1 year of therapy. Mean ferritin decreased from 3363.7 +/- 2144.5 microg/L to 2323.2 +/- 1740.8 microg/L (P < 0.0001). The reduction was significant even in the group of patients with ferritin <2500 microg/L. Significant improvement in T2 relaxation and SF was observed. The most common adverse events were gastrointestinal symptoms (20%) and transaminasemia (18%). The rate of agranulocytosis was 4.2 cases per 100 patient-years. Prolonged use of combined therapy with DFP and DFO is effective in decreasing iron load and improving cardiac function. Its possible association with higher incidence of agranulocytosis emphasizes the need for close monitoring.

Longitudinal study of survival and causes of death in patients with thalassemia major in Greece.

Iron-induced organ degeneration is the main factor of mortality in patients with thalassemia major. Since chelation therapy is at a turning point, from the laborious parenteral route to the use of new promising oral agents, we investigated the current status of survival of these patients to present reliable data that will be useful in future comparative studies. Survival probabilities were estimated by the Kaplan-Meier method, and results were compared by the log-rank test in a total of 647 thalassemic patients (pts) (52% males) born between 1/1/58 and 1/2/04. Terminal follow-up was 1/12/04. All transfusion-dependent pts monitored in our center, or in frequent contact if they had moved elsewhere, were strictly selected, excluding all rarely transfused or intermediate cases. Pts born before 1/1/75 were classified in group A (n = 366), while pts born later were included in group B (n = 281). According to the last 5 years' mean serum ferritin level, pts were divided into three hemosiderosis groups: (1) mild (<2000 microg/L) 49%, (2) moderate (2000-4000 microg/L) 28%, and (3) severe (>4000 microg/L) 23%. Of the 647 pts, 115 died (mean age: 22.6 +/- 6.2 years), most frequently by heart failure (71.3%) followed by sepsis (7.8%). Life expectancy in the entire population was up to 59% at 46 years. Survival was higher for pts born after 1975 than those before (P < .001). Statistically significantly different survival probabilities were found between groups with mild, moderate, or severe hemosiderosis (P < .001). Effective management with improved chelation therapy could lead to better results.