Non-Invasive Monitoring of Hepatic Iron Concentration during Oral Chelation in Patients with Non-Regularly Transfused β-Thalassemia/Hb E Disease.

Abstract Current non-invasive measurement techniques of hepatic iron concentration (HIC) include magnetic susceptometry (SQUID) and the magnetic resonance imaging (MRI) methods utilising T2 and T2*. HIC can be quantified through image measurement of the proton transverse relaxation rate (R2) (St. Pierre et al Blood 2004). The potential for using the St Pierre method to monitor changes in HIC of patients with β-thalassemia/Hb E undergoing iron chelation therapy was investigated. Seventeen non-tansfusion dependant β-thal/Hb E patients who had not previously undergone chelation were studied. Subjects were chelated with the oral iron chelator Deferiprone (DFP) and had their HIC measured using both the R2-MRI and biopsy non-heme iron techniques pre and post treatment. Ferritin levels were also assayed for comparison. The subjects ages ranged from of 13 to 53 years (mean 31.6, SD 11.5). DFP was administered at a low dose of 50 mg/kg/Day with divided doses 2 –3 times daily. The periods of drug exposure ranged between 53 and 77 weeks (mean 64.1, SD 8.4). HIC by R2-MRI and tissue iron chemical analysis, and serum ferritin Measurement R2-HIC (mg/g DW) Biopsy-HIC (mg/g DW) Serum Ferritin (ng/ml) Mean ± SD Range Mean ± SD Range G.Mean ± SE Range Initial 17.8 ± 6.6 5.7 – 29.7 18.3 ± 9.0 6.0 – 40.1 2526 ± 432 842 – 6072 Final 8.4 ± 7.9 1.0 – 23.9 7.4 ± 7.3 0.2 – 25.5 416 ± 236 113 – 4030 The results show a significant decrease of HIC after long term administration of DFP with MRI and biopsy (p= .0004 and p<0.0001 respectively). Spearman rank correlations of R2-HIC with the liver non-heme Fe and serum ferritin measures gave positive values of 0.866 (p < 0.0001) and 0.768 (p < 0.0001) respectively. The mean reduction of R2-HIC, biopsy-HIC and serum ferritin were 53%, 69%, and 74%, respectively. A decrease of 20.5% (SD ±14.9%) in the standard deviation of the R2 distribution was observed suggesting a decrease in iron heterogeneity accompanied the mean HIC decrease. The results suggest that R2 MRI has the potential to be used as a clinical monitoring tool in chelation therapy.