Long‐term use of deferiprone significantly enhances left‐ventricular ejection function in thalassemia major patients

Abstract

A multicenter randomized open-label long-term sequential deferiprone-deferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].Serial observations of LVEF over 3 years, in the same patient, were retrospectively assessed in 99 patients with TM during the sequential DFP-DFO multicenter randomized open-label trial [1]. A generalized estimating equation (GEE) model was used to demonstrate changes in mean LVEF over time [2].The regression coefficient of treatment suggested that the DFP-alone group showed a statistically significant increase in mean LVEF over time (coefficient 0.97, 95% CI (0.51; 1.44), P-value <0.0001).These findings suggest that long-term treatment with DFP-alone can significantly enhance LVEF over time. These findings agree with a survival analysis reporting a substantial decline in cardiac deaths during recent years, related to the switching of high-risk patients from DFO to chelation regimens that include the oral chelator DFP [3][4][5].Oral chelation treatment has improved greatly adherence and management of patients with TM [6,7].The improvement of the LVEF after 1-year DFP treatment has been reported [8][9][10][11].However, the effects of DFP on LVEF after long-term treatment have not been fully investigated.This letter reports a retrospective survey performed on patients with TM, previously enrolled in a long-term randomized open-label trial carrying ahead in Italy on the behalf of the Italian Society for the Study of Thalassaemia and Haemoglobinopathies (SoSTE) [1]. Ninety-nine out of 213 patients enrolled in the sequential DFP-DFO trial underwent longterm echocardiographic study of LVEF measured at baseline and every 12 months over three consecutive years (Fig. 1). Among these, 39 and 60 received sequential DFP (75 mg/kg for 4 days/week)-DFO (50 mg/kg for 3 days/week) or DFP-alone (75 mg/kg for 7 days/week) treatment, respectively (Table I).The hematological and clinical findings at enrollment are shown in Table I. No differences were observed at baseline between the two randomized groups. Particularly, the main findings of body iron overloading, expressed as serum ferritin at baseline, liver iron concentration (LIC), baseline LVEF <55%, and total number of blood transfusions were not statistically significantly different (Table I). Moreover, although baseline LVEF appears unlike between the two groups ( Fig. 1), this was not statistically significantly different (P-value 5 0.10, Table I).The DFP-alone group showed statistically significant increase over time in mean LVEF in comparison with sequential DFO-FP treatment (coefficient 0.97, 95% CI (0.51; 1.44), P-value <0.0001).Furthermore, the regression coefficient of treatment suggested that there was a statistically significant difference in mean LVEF between the two treated groups favoring the sequential group (coefficient 2.36, 95% CI (0.02; 4.71), P-value 5 0.047, but this ...

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

“…Cardio-protective effect of defeferiprone is one of its important clinical effects which has been shown to be associated with improved long term survival by reducing cardiac related mortality in thalassemia major patients [32][33][34]. In our present study, the majority of patients had normal levels of cardiac T2* (> 20 msec.)…”

Cardiovascular Function and Treatment in β-Thalassemia Major

“…Data from control arms of 2 randomized controlled trials showed subcutaneous deferoxamine did not significantly improve LVEF in mild to moderate cardiac iron overload, 8,9 whereas the active arms of these trials showed significant increases in LVEF with deferiprone, 8,9 and this has been found in other trials. 276 These findings are in accordance with those of cross-sectional studies. 240,248 LVEF does not increase with deferasirox treatment in cardiac siderosis.…”

Longitudinal monitoring of cardiac siderosis using cardiovascular magnetic resonance T2* in patients with thalassemia major on various chelation regimens: A 6‐year study

“…(10) This may be partly due to poor compliance (11, 12) and the lack of ability to monitor cardiac iron load. Electrocardiography (13) and 2D-echocardiography (14) have been used to correlate cardiac function with iron deposition with some success. Recently, CMR has allowed accurate measurement of iron excess in the heart and can be a better guide for managing iron chelation therapy with single or a combination of chelators.…”