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 ± 0.10mg/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 μM). 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.
Rare Disease Center, Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy.
E
E
Cassinerio
Rare Disease Center, Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy.
N
N
Orofino
CMR Unit, Department of Cardiology, Niguarda Ca' Granda Hospital, Milan, Italy.
A
A
Roghi
Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy.
L
L
Duca
Department of Clinical Sciences and Community Health, University of Milan, Italy.
E
E
Poggiali
Second Division of Gastroenterology, "Ca' Granda" Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy.
M
M
Fraquelli
Rare Disease Center, Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy.
L
L
Zanaboni
Rare Disease Center, Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy; Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Italy.
M D
MD
Cappellini
D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000627:therapeutic use*; D015913:Chelation Therapy; D000077588:Deferasirox; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019190:Iron Overload / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000150:complications*
D001565:Benzoates; D014230:Triazoles; D003676:Deferoxamine; D000077588:Deferasirox
Cardiac iron overload; Chelation therapy; Deferasirox; Deferoxamine; Thalassemia major