Efficacy of Iron Chelation in Reducing Cardiac Iron as Assessed by MRI T2* in Patients with Thalassemia Major
Authors: Berdoukas Vasilios Antonios , Chouliaras Giorgos , Moraitis Panagiotis , Zannikos Kirikos , Berdoussi Eleni , Ladis Vassilis 
Published: October 2019

241 thalassemia major patients have had repeated evaluation of cardiac iron assessed by Magnetic Resonance Imaging (MRI) over a median interval of 15 months (range 2.6–72.6). We compared changes in T2* between MRI studies with desferrioxamine (DFO) – (number of patients (n)=31, total MRIs (nMRI)=116), deferiprone (DFP) − (n=41 nMRI=94) and combination of DFO and DFP (Comb) − (n=143 nMRI=347) using repeated measurement analysis with correlated error terms and time varying covariates. Patients were divided into four groups according to their baseline cardiac T2* (Heavy load £ 8 ms, moderate load 8–14, mild 314–20 and normal 320). Table 1 shows the overall assessment excluding patients on DFX. These were not included in that assessment as the total period of exposure was statistically significantly less than that of the other regimes. Analysis was therefore performed using student T test to assess the rate of change between the first and second MRI in the T2* values in patients with comparable cardiac siderosis according to each chelation regime adjusted for overall time of exposure (Table 2). With linear regression analysis (Table3) we compared the effect of DFO to the other three regimes in the annual rate of increasing cardiac T2*. The results have been adjusted for baseline T2* and time of exposure to therapy. Both DFP and Comb regimes are superior to DFO in reducing cardiac siderosis. This indicates that over one year DFP and Comb regimes will have a greater increase in T2* than that achieved by DFO. In addition, Comb seems to be superior to DFX as it would increase the T2* by 2ms/year above that which can be achieved by DFX (p=0.007). DFP achieves 1.7ms/year above the annual improvement with DFX but the difference is not statistically significant. The estimated difference in annual improvement of T2* between Comb and DFP is 0.33ms/year (p=0.07) These data confirm that which is seen in clinical practice according to the chelation regimes used. It is clear that the combination of DFO and DFP is the most rapid regime for reducing cardiac iron and seems to be effective at all levels of cardiac siderosis. The ability to assess tissue iron in the heart is extremely clinically valuable and allows preemptive intervention in order to reduce cardiac morbidity and mortality by the selection of the most appropriate chelation therapy according to the MRI findings.

Table1 Annual estimated mean change in T2* according to severity of cardiac siderosis

Regime Heavy Moderate Mild ΔT2* p ΔT2* p ΔT2* p DFO 0.61 n.s 1.06 n.s. −1.5 n.s. DFP 0.55 <0.001 2.8 <0.001 3.4 <0.001 Comb 1.4 <0.001 3.5 <0.001 2.6 <0.001

Table 2 Annual estimated mean change in T2* according to severity of cardiac siderosis

Regime Heavy Moderate Mild ΔT2* P ΔT2* p ΔT2* p *tm= mean time (in months) between MRI studies DFO n= 73 tm*= 23 0.73 0.05 1.07 0.09 0.9 0.4 DFP n= 53 tm=18.5 1.95 0.14 3.2 0.0045 3.9 0.06 Comb n= 152 tm=21.2 1.98 <0.001 4.4 <0.001 5.7 0.0025 DFX n=96 tm=14.9 −0.51 0.41 −0.67 0.4 4.2 0.23

Table 3

Mean estimated difference in T2* Standard Error p DFP v. DFO 2.1 0.99 0.033 Comb v DFO 2.4 0.69 <0.001 DFX v DFO 0.44 0.82 0.6