MRI multicentre prospective survey in thalassaemia major patients treated with deferasirox versus deferiprone and desferrioxamine

Abstract

Summary We prospectively assessed the efficacy of deferasirox versus deferiprone or desferrioxamine as monotherapy in thalassaemia major (TM) patients by magnetic resonance imaging (MRI). We selected the patients enrolled in the Myocardial Iron Overload in Thalassaemia network who received only one chelator between two MRIs (deferasirox = 235, deferiprone = 142, desferrioxamine = 162). Iron overload was measured by T2* technique and biventricular function by cine images. Among the patients with baseline myocardial iron, in all three groups there was a significant improvement in global heart T2* values. The deferiprone and desferrioxamine groups showed a significant improvement in left ventricular ejection fraction (LVEF). Only the deferiprone group showed a significant improvement in right ventricular ejection fraction (RVEF). The improvement in global heart T2* was significantly lower in the deferasirox versus the deferiprone group. The improvement in the LVEF was significantly higher in the deferiprone and desferrioxamine groups than in the deferasirox group and the improvement in the RVEF was significantly higher in the deferiprone than in deferasirox group. Among the patients with baseline hepatic iron, the changes in hepatic iron were comparable in deferasirox versus the other groups. Deferasirox monotherapy was less effective than deferiprone in improving myocardial siderosis and biventricular function and less effective than desferrioxamine in improving the LVEF.

ECONOMIC EVALUATION OF CHELATION REGIMENS FOR Β--Thalassemia MAJOR: A SYSTEMATIC REVIEW

“…Cardiac complications are reported to be the cause of the deaths in 71% of these patients 26,27. A multicentre prospective survey showed that DFO, DFP, and DFX monotherapies not only in removing iron from the liver, but also in improving myocardial siderosis and biventricular function 28. When the efficacy of DFO or DFP monotherapy is low, combination therapy of DFO and DFP (DFO+DFP) can be used.…”

Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases

“…Similar combinations of DFO and DFRA or L1 and DFRA, as well as other intensive chelation protocols have been tested. Unfortunately, as of now, neither improvements in safe iron removal, nor maintenance of iron at physiological levels have been reported yet, possibly due to iron-toxicity implications [ 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ]. Overall, it appears that L1 is necessary for the achievement of the ultimate aim of iron chelation therapy, i.e., the achievement and maintenance of normal iron stores in regularly transfused and other categories of iron loaded patients [ 110 , 111 , 120 ].…”

The History of Deferiprone (L1) and the Complete Treatment of Iron Overload in Thalassaemia

“…57,88 There are many variables in the properties and mode of action of chelating drugs and the selection of any chelation protocol could have a direct effect on the mortality and morbidity of thalassaemia patients ( Table 3). [5][6][7][8][9][10][57][58][59][60] Optimum iron chelation therapies in the context of personalised medicine in thalassaemia patients take into consideration the most effective and less toxic monotherapy or combination therapy protocols. 61 In this context, for each patient, the dose protocols are adjusted with regards to the iron load and the efficacy/tolerability of the chelation therapy.…”

“…However, the relatively recent routine introduction of new diagnostic techniques such as Magnetic Resonance Imaging (MRI) T2 and T2* which identify the level of iron load in the heart, liver, spleen and other organs of thalassaemia and other iron overloaded patients, has not only increased our understanding of transfusional and other iron overload metabolic pathways but also the differential effect of chelating drugs in iron removal from various organs. 60,[69][70][71][72][73] The recent diagnostic procedures, and especially MRI T2 and T2* in the determination of iron deposition in organs, have increased the prospects of improved chelating drug targeting therapies of iron overload toxicity, as well as the introduction of personalised chelation regimens in thalassaemia and other iron overload metabolic disorders. 73 Furthermore, based on these diagnostic findings the complete treatment of iron overload by removing all excess iron safely from the heart, liver and other organs of regularly TDT patients using L1, the L1/DF or other chelator combinations can nowadays be precisely monitored (Figure 6).…”

“…8,81,83 This proposition is supported by recent detailed monitoring findings in the improvement in cardiac iron depletion rate and cardiac function by L1 and L1/DF over other therapies. 60,100 Advances in the constant monitoring of iron deposition in critical organs like heart, liver, and pancreas by MRI T2* has recently allowed improvement in the tailoring iron chelation therapy and the selection of the more appropriate chelation regimens in different clinical cases, thus reducing overall patient mortality and morbidity. [101][102][103] The limitations in the use of L1 and the L1/DF combination in some countries may constitute an irregular action by health policy decision makers and also negligence in relation to the well being of thalassaemia patients.…”