Combination of deferasirox and deferoxamine in clinical practice: An alternative scheme of chelation in thalassemia major patients

The availability of three iron chelators improved the scenario of chelation therapy for transfusion-dependent thalassemia (TDT) patients, allowing tailoring of drugs according to the goals expected for each patient. The use of Deferiprone/Deferoxamine (DFP/DFO) combined in different schemes has been reported since many years. Only recently data from combination of Deferasirox/Deferoxamine (DFX/DFO) have been reported showing that it can be safe and efficacious to remove iron overload, particularly in patients who do not respond adequately to a single chelating agent. We investigated the efficacy, tolerability and safety of combined DFX/DFO in thalassemia major patients. Ten TDT patients have started DFX/DFO for different reasons: 1) lack of efficacy in removing liver/cardiac iron with monotherapy; 2) agranulocytosis on DFP; and 3) adverse events with elevated doses of monotherapies. The study design included: cardiac and hepatic T2* magnetic resonance (CMR), transient elastography evaluation (Fibroscan), biochemical evaluation, and audiometric and ocular examinations. The drugs' starting doses were: DFO 32 +/- 4 mg/kg/day for 3-4 days a week and DFX 20 +/- 2 mg/kg/day. Seven patients completed the one-year follow-up period. At baseline the mean pre-transfusional Hb level was 9.4 +/- 0.4 g/dl, the mean iron intake was 0.40 +/- 0.10 mg/kg/day, the median ferritin level was 2254 ng/ml (range 644-17,681 ng/ml). Data available at 1 year showed no alteration of renal/hepatic function and no adverse events. A marked reduction in LIC (6.54 vs 11.44 mg/g dw at baseline) and in median ferritin (1346 vs 2254 ng/ml at baseline) was achieved. A concomitant reduction of non-transferrin-bound iron (NTBI) at six months was observed (2.1 +/- 1.0 vs 1.7 +/- 1.2 mu M). An improvement in cardiac T2* values was detected (26.34 +/- 15.85 vs 19.85 +/- 12.06 at baseline). At 1 year an increased dose of DFX was administered (27 +/- 6 mg/kg/ day vs 20 +/- 2 mg/kg/day at baseline, p = 0.01) with a stable dose of DFO (32 +/- 4 mg/kg/day). Combined or alternated DFX/DFO can be considered when monotherapy is not able to remove the iron overload or in the presence of adverse events. (C) 2014 Elsevier Inc. All rights reserved.