Most deaths in beta-thalassemia major result from cardiac complications due to iron overload. Differential effects on myocardial siderosis may exist between different chelators. A randomized controlled trial was performed in 61 patients previously maintained on subcutaneous deferoxamine. The primary end point was the change in myocardial siderosis (myocardial T2*) over 1 year in patients maintained on subcutaneous deferoxamine or those switched to oral deferiprone monotherapy. The dose of deferiprone was 92 mg/kg/d and deferoxamine was 43 mg/kg for 5.7 d/wk. Compliance was 94% ؎ 5.3% and 93% ؎ 9.7% (P ‫؍‬ .81), respectively. The improvement in myocardial T2* was significantly greater for deferiprone than deferoxamine (27% vs 13%; P ‫؍‬ .023). Left ventricular ejection fraction increased significantly more in the deferipronetreated group (3.1% vs 0.3% absolute units; P ‫؍‬ .003). The changes in liver iron level (؊0.93 mg/g dry weight vs ؊1.54 mg/g dry weight; P ‫؍‬ .40) and serum ferritin level (؊181 g/L vs ؊466 g/L; P ‫؍‬ .16), respectively, were not significantly different between groups. The most frequent adverse events were transient gastrointestinal symptoms for deferipronetreated patients and local reactions at the infusion site for deferoxamine. There were no episodes of agranulocytosis. Deferiprone monotherapy was significantly more effective than deferoxamine over 1 year in improving asymptomatic myocardial siderosis in beta-thalassemia major. (Blood. 2006;107: 3738-3744)

The authors represent a cooperative group of 15 institutions that examined the feasibility of using metabolic fea tures observed in vivo with 'H-magnetic resonance (MR) spectroscopy to characterize brain tumors of the glial type.The institutions provided blinded, centralized MR spectroscopy data processing along with independent central review of MR spectroscopy voxel placement, composition and contamination by brain, histopathological typing using current World Health Organization criteria, and clinical data, Proton 'H-MR spectroscopy was performed using a spin-echo technique to obtain spectra from 8-cc voxels in the tumor and when feasible in the contralateral brain. Eighty-six cases were assessable, 41 of which had contralateral brain spectra. Glial tumors had significantly elevated intensities of choline signals, decreased intensities of creatine signals, and decreased intensities of N-acetyl asp art ate compared to brain. Choline signal intensities were highest in astrocytomas and anaplastic astrocytomas, and creatine signal intensi ties were lowest in glioblastomas. However, whether expressed relative to brain or as intratumoral ratios, these meta bolic characteristics exhibited large variations within each subtype of glial tumor. The resulting overlaps precluded diagnostic accuracy in the distinction of low-and high-grade tumors. Although the extent of contamination of the ]H-MR spectroscopy voxel by brain had a marked effect on metabolite concentrations and ratios, selection of cases with minimal contamination did not reduce these overlaps. Thus, each type and grade of tumor is a metabolically hetero geneous group. Lactate occurred infrequently and in all grades. Mobile lipids, on the other hand, occurred in 41% of high-grade tumors with higher mean amounts found in glioblastomas. This result, coupled with the recent demonstra tion that intratumoral mobile lipids correlate with microscopic tumor cell necrosis, leads to the hypothesis that mobile lipids observed in vivo in E H-MR spectroscopy may correlate independently with prognosis of individual patients. W. G. Negendank, et ciL rylcholine), one primarily from creatines (creatine and phosphocreatine), and one primarily from acetyl aspar tate (NAA), In disease, signals from lactate and mobile lipids may also be observed.Studies of extracts of surgical specimens of human as trocytic tum ors using ]H -N M R spectroscopy indicated an increase in the ratio o f cholines to creatines, and a decrease in the ratio of N A A to creatines, with increas ing histopathological grades of m alignancy.16,45'61 Studies in patients using !H-N M R spectroscopy, referred to as MR spectroscopy, indicated sim ilar correlations betw een m etabolic features in vivo and the histopathological grades of astrocytic tum ors. 4'11'14'21,32,43'57'58'61 Other MR spectroscopy studies indicated that lactate is more likely to be present in high-than in low-grade tumors4, 14,15'20'21 and that the am ount of lactate may correlate with the extent of hyperm etabolic glucose consumption sho...

Recent advances in magnetic resonance imaging (MRI) techniques allow the assessment of iron overload in tissues 1 especially the heart, 2 in transfusion-dependent thalassemia patients. The R2* value (1/T2*) recorded in the intraventricular septum of the heart indirectly measures the degree of cardiac iron load. Applying this new technology we looked at a number of historical and biochemical parameters in order to determine their relationship to cardiac iron overload and the effect of cardiac iron on functional and structural changes of the heart in transfusion-dependent thalassemics. Haematologica 2007; 92:131-132

Myocardial iron deposition occurs as a result of blood transfusion therapy in b-thalassemia major patients. Since this deposition causes various cardiac complications, it is of interest to assess the iron content of the myocardium in relation to the clinical picture of the patients. Two different MRI indices were used to achieve this purpose: the T2 relaxation time and the heart/skeletal muscle signal intensity ratio. ECG gated spin echo images were obtained from 54 adult thalassemic patients, with a mean age of 26 (18-44) years, at TE = 22 ms and 60 ms, using a 1.5 T system. Patients were divided into 2 groups (A and B), according to their serum ferritin levels (> or < 2000 ng ml(-1)). Results were compared with nine controls, with a mean age of 25 (18-43) years. Heart T2 relaxation time in controls (44.3 +/- 3.5 ms) was higher than in group A (29.9 +/- 5.7 ms, P < 0.001) and group B (33.4 +/- 6.8 ms, P < 0.01). T2 was measurable in 66% of group A and 83% of group B patients. The heart/muscle signal intensity ratio in group A (0.45 +/- 0.27) was lower than in group B (0.82 +/- 0.33, P < 0.001) and the controls (1.15 +/- 0.20, P < 0.001). The heart/muscle signal intensity ratio was measurable in 94% of the patients and demonstrated an inverse relationship with the serum ferritin levels (r = -0.52, P < 0.01). This study indicates that the heart/muscle ratio is a sensitive index of iron overload and it can be measured in the majority of patients, irrespective of tissue iron concentration, thereby offering an advantage over the use of T2 relaxation time.

Summary Recently introduced chelation regimens that combine deferoxamine (DFO) and deferiprone have been shown to have greater efficacy in promoting iron excretion than either chelator alone and have been associated with rapid reduction of the iron load in the heart and liver, and with reversal of cardiac dysfunction. It is unclear whether this combined therapy could be associated with a reduction in iron load or decline in the severity of iron‐induced endocrinopathies. Starting in January 2001, 42 patients with β‐thalassaemia major, previously maintained on subcutaneous DFO only, were switched to combined treatment with DFO and deferiprone. The primary endpoint was to investigate the effects of this therapy on the glucose metabolism characteristics of this population. Combination therapy markedly decreased ferritin levels (638 ± 1345 vs. 2991 ± 2093 μg/l, P < 0·001). Glucose responses were improved at all times during an oral glucose tolerance test, particularly in patients in early stages of glucose intolerance. Glucose quantitative secretion also decreased significantly with combined therapy, while no significant change occurred in insulin levels in any group. Insulin secretion, according to the homeostasis assessment model, markedly increased in all groups, while overall reduction in insulin sensitivity did not reach statistical significance. This study showed that the combination of DFO and deferiprone was associated with an improvement in liver iron deposition and glucose intolerance.