PB2389 UNDERDOSING DEFERIPRONE IN TM: MYTH OR REALITY?

Abstract

Background:Data from clinical practice show that some patients with thalassemia major (TM) received underdoses of deferiprone (DFP).Aims:This retrospective real‐life study aimed to investigate the reasons of the underdosing of DFP and to assess if the underdosing could result in an inadequate response.Methods:Among the 1746 TM patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network between 2006 and 2015, we selected the 171 consecutively patients (100 M and 71 F) patients who were treated with DFP dosages<75 mg/Kg/day. Mean age at starting underdosed therapy was 30.95 ± 8.78 years. Heart and liver iron overload were measured by T2∗ Magnetic resonance imaging (MRI) technique.Results:Fifty‐four patients were treated with DFP in monotherapy (60.31 ± 12.82 mg/kg/die for 6.96 ± 0.19 days/week), 87 with combined DFP + deferoxamine (DFO) therapy (52.28 ± 21.29 mg/kg/die for 6.00 ± 1.43 days/week), and 30 with sequential DFO/DFP therapy (60.53 ± 9.75 mg/kg/die for 4.07 ± 0.69 days/week).Table 1 shows the motivations of underdosage, divided by chelation regimens. The most frequent motivation was the weight‐driven adjustment of the dosage, followed by the presence of low ferritin levels and side effects (gastric disturbances = 14/33 pts, increase of transaminases 6/33 pts and neutropenia 5/33).Sixty‐eight patients maintained the same chelation regimen (24 monotherapy, 27 combined and 17 sequential) during the execution of two consecutive MRI scans, performed in a time span of 18 months. At the first MRI 17 patients showed myocardial iron overload (MIO‐global heart T2∗ value<20 ms). In this subgroup there was a significant increase of global heart T2∗ values (12.39 ± 3.77 ms vs 20.43 ± 10.71 ms; P = 0.002) and six (35.3%) patients reached a global heart T2∗ > 20 ms at the second MRI. None of the 51 patients with a normal global heart T2∗ value at the first MRI showed MIO at the second MRI. In the 39 patients with hepatic iron overload (MRI liver iron concentration‐LIC≥3 mg/g dw) at the first MRI, there was not a significant decrease in LIC values, although 7 (17.9%) patients reached a normal value at the second MRI. Out of the 21 patients with a normal LIC value at the first MRI, 5 (17.2%) showed hepatic iron at the second MRI.Summary/Conclusion:In the real world the weight‐driven adjustment of the dosage, low ferritin levels and sides effects were the main causes of the DFP underdosage in TM. DFP dosages<75 mg/Kg/day can be effective in improving myocardial siderosis but do not allow an improvement in terms of hepatic iron.image