Deferiprone has a dose-dependent effect on liver iron concentration assessed by MRI
Antonella Meloni1, Vincenzo Positano1, Gianluca Valeri2, Gennaro Restaino3, Chiara Tudisca4, Paolo Preziosi5, Elisabetta Chiodi6, Maria Giovanna Neri1, Stefano Pulini7, Basilia Piraino8, Petra Keilberg1, and Alessia Pepe1

1Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy, 2Azienda Ospedaliero-Universitaria Ospedali Riuniti "Umberto I-Lancisi-Salesi", Ancona, Italy, 3Fondazione di Ricerca e Cura "Giovanni Paolo II", Campobasso, Italy, 4Policlinico "Paolo Giaccone", Palermo, Italy, 5Policlinico “Casilino", Roma, Italy, 6Arcispedale “S. Anna”, Ferrara, Italy, 7Ospedale Civile “Spirito Santo”, Pescara, Italy, 8Policlinico "G. Martino", Messina, Italy

Synopsis

The aim of this multi-centre study was to retrospectively assess in thalassemia major (TM) if deferiprone (DFP) had a dose-dependent effect on liver iron concentration (LIC) assessed by quantitative magnetic resonance imaging (MRI). We found out that the percentage of patients that worsened their status was significantly higher in patients with ≤ 75 mg/kg/d than in patients with > 75 mg/kg/d (26.6% vs 7.7%; P=0.016). So, the worsening in MRI LIC can be prevented by increasing the dose of deferiprone above the widely used regimen of 75 mg/kg body weight.

Aim

The aim of this multi-centre study was to retrospectively assess in thalassemia major (TM) if deferiprone (DFP) had a dose-dependent effect on liver iron concentration (LIC) assessed by quantitative magnetic resonance imaging (MRI).

Methods

Among the 958 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network [1], we identified hose with an MRI follow up study at 18±3 months who had been received DFP monotherapy and had no changes in dose of DFP between the 2 MRI scans.

Patients were divided into two groups according to the DFP dose: 79 patients with ≤ 75 mg/kg/d (group 1) and 39 with > 75 mg/kg/d (group 2).

Hepatic iron overload was measured by the T2* multiecho technique [2] and T2* values were converted into LIC values using the calibration curve introduced by Wood et al [3].

Results

The two groups had comparable baseline MRI LIC values. The Table shows the evolution of different iron overload risk classes between the baseline and the FU MRI. The percentage of patients that worsened their status was significantly higher in group 1 than in group 2 (26.6% vs 7.7%; P=0.016).

Subgroup analysis in patients with hepatic iron overload at baseline (MRI LIC > 3mg/g/dw) was conducted: 48 patients from group 1 (DFP dose: mean 70.6±11.2 mg/kg/d, median 75 mg/kg/d) and 30 from group 2 (DFP dose: mean 85.2±6.6 mg/kg/d, median 84 mg/kg/d). The two subgroups had comparable baseline MRI LIC values (10.2±8.1 mg/g dw vs 11.1±8.7 mg/g dw (P=0.314). While the mean change in subgroup 2 (-1.8±6.3mg/g/dw, P=0.131) was more favourable than in subgroup 1 (+0.1±7.7 mg/g/dw, P=0.903), the change in MRI LIC values did not reach statistical significance between the two subgroups (P=0.579) (Figure 1), which may be due to small cohort evaluated.

Conclusions

In TM patients the worsening in MRI LIC can be prevented by increasing the dose of deferiprone above the widely used regimen of 75 mg/kg body weight. Our results are consistent with the iron balance studies performed by Grady RW et al [4].

Acknowledgements

We thank all the colleagues of the MIOT Network (https://miot.ftgm.it).

The MIOT project receives “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc.).

References

[1] Meloni A et al. Int J Med Inform 2009;78:503-12.

[2] Meloni A et al. J Magn Reson Imaging 2011;33:348-55.

[3] Wood JC et al. Blood 2005;106:1460-5.

[4] Grady RW et al. Haematologica 2013;98:129-35.

Figures

Table 1. Evolution of different LIC risk classes between the baseline and the FU MRI. The underlined numbers represent the patients who remained in the same risk class. The numbers on the right of the underlined numbers indicate the patients who switched to an higher risk class while the numbers on the left indicate the patients who switched to a lower risk class.

Figure 1. Mean changes of MRI LIC values in patients with hepatic iron at the baseline MRI.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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