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.