Abstract 5298

Introduction:

Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluate quantitatively the changes in cardiac and hepatic iron and in cardiac function in thalassemia major (TM) patients under different chelation regimens. This study aimed to prospectively assess the efficacy of the sequential deferiprone–deferrioxamine (DFP-DFO) versus deferiprone (DFP) and deferrioxamine (DFO) in monotherapy in a large cohort of TM patients by quantitative MR.

Methods:

Among the first 1135 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 392 patients performed a MR follow up study at 18±3 months. We evaluated prospectively the 35 patients treated with DFP-DFO versus the 39 patients treated with DFP and the 74 patients treated with DFO between the 2 MR scans. Iron concentrations were measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images.

Results:

Excellent/good levels of compliance were similar in the DFP-DFO (97.1%) versus DFP (94.9%) and DFO (95.9%) groups. No significant differences were found in the frequency of side effects in DFP-DFO (15.6%) versus DFP group (9.4%). The percentage of patients who maintained a normal global heart T2* value (≥20 ms) was comparable between DFP-DFO (96%) versus DFP (100%) and DFO (98.1%) groups.

Among the patients with myocardial iron overload (MIO) at baseline (global heart T2*<20 ms), in all three groups there was a significant improvement in the global heart T2* value (DFO-DFP: P=0.004, DFP: P=0.015 and DFO: ms P=0.007) and a significant reduction in the number of pathological segments (DFO-DFP: P=0.026, DFP: P=0.012 and DFO: P=0.002). In DFO-DFP and DFP groups there was a significant increment in the left ventricular (LV) ejection fraction (EF) (P=0.035 and P=0.045, respectively) as well as in the right ventricular (RV) EF (P=0.017 and P=0.001, respectively). The improvement in the global heart T2* and in biventricular function were not significantly different in DFO-DFP compared to the other groups (Table 1).

Table 1.

Inter-treatment (DFP-DFO vs DFP and DFP-DFP vs DFO) comparisons in terms of changes between the two MRs in patients with global heart T2* <20 ms.

PDFP (n = 9)DFP-DFO (n = 10)DFO (n = 21)P
Mean Diff. Global Heart T2* (ms) 0.195 +8.8 ± 8.6 +4.8 ± 3.9 3.7 ± 5.5 0.581 
Mean Diff. N seg. with T2* < 20 ms 0.214 −6.0 ± 5.6 −3.2 ± 3.8 −2.9 ± 3.7 0.838 
Mean Diff. LV EF (%) 0.800 +5.0 ± 6.4 +4.3 ± 5.1 +2.0 ± 6.2 0.330 
Mean Diff. RV EF (%) 0.941 +6.8 ± 3.7 +6.7 ± 6.6 +0.2 ± 8.8 0.058 
Mean Diff. Ferritin (ng/ml) 0.259 −113 ± 241 −333 ± 516 −133 ± 575 0.362 
PDFP (n = 9)DFP-DFO (n = 10)DFO (n = 21)P
Mean Diff. Global Heart T2* (ms) 0.195 +8.8 ± 8.6 +4.8 ± 3.9 3.7 ± 5.5 0.581 
Mean Diff. N seg. with T2* < 20 ms 0.214 −6.0 ± 5.6 −3.2 ± 3.8 −2.9 ± 3.7 0.838 
Mean Diff. LV EF (%) 0.800 +5.0 ± 6.4 +4.3 ± 5.1 +2.0 ± 6.2 0.330 
Mean Diff. RV EF (%) 0.941 +6.8 ± 3.7 +6.7 ± 6.6 +0.2 ± 8.8 0.058 
Mean Diff. Ferritin (ng/ml) 0.259 −113 ± 241 −333 ± 516 −133 ± 575 0.362 

Among the patients with hepatic iron at baseline (T2*<9.2 ms), only in DFO group there was a significant improvement in the liver T2* value (2.0±3.5 ms P=0.010). Liver T2*changes were not significantly different in DFO-DFP versus the other groups.

Conclusions:

Prospectively we did not find significant differences on cardiac and hepatic iron or in cardiac function in TM patients treated with sequential DFP–DFO therapy versus the TM patients treated with DFO or DFP in monotherapy.

Disclosures:

Pepe:Novartis: Speakers Bureau; Apotex: Speakers Bureau; Chiesi: Speakers Bureau. Off Label Use: Association of two chelators commercially available in order to obtain a higher efficacy. Lai:Novartis: Honoraria, Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.