Iron-chelating therapy with deferasirox in transfusion-dependent, higher risk myelodysplastic syndromes: a retrospective, multicentre study.

Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375-2500 mg) for a median of 11 months (range 0·4-75). Eight patients (16%) showed grade 2-3 toxicities (renal or gastrointestinal), 4 of whom (8%) required drug interruption. Median ferritin levels decreased from 1709 µg/l at baseline to 1100 µg/l after 12 months of treatment (P = 0·02). Seventeen patients showed abnormal transaminase levels at baseline, which improved or normalized under DFX treatment in eight cases. One patient showed a remarkable haematological improvement. At a median follow up of 35·3 months, median overall survival was 37·5 months. The results of this first survey of DFX in HR-MDS are comparable, in terms of safety and efficacy, with those observed in lower-risk MDS. Though larger, prospective studies are required to demonstrate real clinical benefits, our data suggest that DFX is feasible and might be considered in a selected cohort of HR-MDS patients.

[The role of iron metabolism in myelodysplastic syndromes]. / Il ruolo del metabolismo del ferro nelle sindromi mielodisplastiche.

Patients affected by myelodysplastic syndromes (MDS) with transfusion-dependent anemia are destined to develop iron overload. The main diagnostic tools for the diagnosis of transfusional iron overload are serum ferritin and transfusion history. In MDS several studies showed that iron overload is an independent negative prognostic factor. Deferasirox, an oral iron chelator, has shown efficacy and acceptable tolerability in MDS setting, and has also been shown to improve peripheral cytopenia in 10-20% of patients. Iron chelation therapy is recommended, after the transfusion of 20 red cell units, in low-risk MDS patients, and also in high-risk patients responding to treatment of the disease and/or candidates to receive allogeneic hematopoietic stem cell transplantation.