TY - JOUR
T1 - Combination of deferasirox and deferoxamine in clinical practice
T2 - An alternative scheme of chelation in thalassemia major patients
AU - Cassinerio, E.
AU - Orofino, N.
AU - Roghi, A.
AU - Duca, L.
AU - Poggiali, E.
AU - Fraquelli, M.
AU - Zanaboni, L.
AU - Cappellini, M. D.
PY - 2014
Y1 - 2014
N2 - 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. 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.
AB - 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. 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.
KW - Cardiac iron overload
KW - Chelation therapy
KW - Deferasirox
KW - Deferoxamine
KW - Thalassemia major
UR - http://www.scopus.com/inward/record.url?scp=84904725111&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904725111&partnerID=8YFLogxK
U2 - 10.1016/j.bcmd.2014.04.006
DO - 10.1016/j.bcmd.2014.04.006
M3 - Article
C2 - 24846580
AN - SCOPUS:84904725111
VL - 53
SP - 164
EP - 167
JO - Blood Cells, Molecules, and Diseases
JF - Blood Cells, Molecules, and Diseases
SN - 1079-9796
IS - 3
ER -