Deferiprone versus deferoxamine in thalassemia intermedia: Results from a 5‐year long‐term Italian multicenter randomized clinical trial

Abstract

In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value 5 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the deferoxamine treatment (P-value 5 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of deferoxamine, suggesting that this drug is an alternative option in cases in which deferoxamine and deferasirox are contraindicated.

The era of comparable life expectancy between thalassaemia major and intermedia: Is it time to revisit the major‐intermedia dichotomy?

“…Heart damage was the leading cause of death in TM while cancer tops the list in TI and is potentially attributed to hepatocellular carcinoma. These differences may be attributed to varying iron chelation and HCV management practices spanning the cohort, which have considerably advanced since 1990 (Borgna-Pignatti et al, 2004a;Maggio et al, 2009a;Brittenham et al, 1994;Calleja et al, 1998;Cunningham et al, 2004;Ladis et al, 2011;Kwiatkowski et al, 2012;Zamani et al, 2015;Kutlar, 2007;Maggio et al, 2002Maggio et al, , 2009bCalvaruso et al, 2015;Wonke et al, 1998;Ambati et al, 2013;Modell et al, 2008;Cappellini et al, 2006;Aydinok et al, 2015;Cassinerio et al, 2015;Collett, 2014); Di Marco et al, 2010). Moreover, the mechanism of iron loading in TI and TM remain different with cardiac damage mostly apparent in TM patients while the liver is more affected in TI, with subsequent clinical consequences (Mariani et al, 2009).…”

“…Standard iron chelation therapy in TM and TI patients (as indicated) was deferoxamine (DFO) as a subcutaneous infusion at a dose of 40-50 mg/kg/day from when it became available in 1965 until 1994. One hundred and fortyfour patients with TM (from September 1994) and 48 patients with TI (from January 2001) started/switched to deferiprone (DFP) treatment (Maggio et al, 2002) in the context of randomized multicentre clinical trials (Maggio et al, 2002(Maggio et al, , 2009bCalvaruso et al, 2015). Combination treatment with DFO and DFP was used from 1998 in TM patients with severe iron overload (Wonke et al, 1998), especially after reports of its effectiveness in controlling cardiac iron overload (Modell et al, 2008;Ambati et al, 2013).…”

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

“…The use of combined Fe chelators to prevent Fe-overload cardiomyopathy in thalassemia has been reported [34, 35]. Moreover, deferiprone is considered similar to deferoxamine in the treatment of thalassemia intermedia [36]. In addition, it has been shown that the oral Fe chelator deferasirox is able to inhibit NF- (nuclear factor-) kB dependent transcription without affecting its proximal activation, resulting in reduced TNF production from T cells stimulated in vitro.…”

Effect of intravenous Deferoxamine concomitant use with blood transfusion on serum ferritin in thalassemia major patients

“…21 Elalfy and et al in a study entitled "Efficacy and safety of a novel combination of two oral chelators Deferasirox/ Deferiprone over Deferoxamine/ Deferiprone in severely iron overloaded young beta thalassemia major patients" showed that both iron chelation combination regimens were equally effective in reducing iron overload and improving Quality Of Life. Deferoxamine/ Deferiprone combination proved superior in improving cardiac T2, treatment compliance, and patient's satisfaction with no greater adverse events.…”