Cardiac effects of deferasirox in transfusion-dependent patients with myelodysplastic syndromes: TELESTO study.

Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion-dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo-controlled, randomised study to evaluate the iron chelator deferasirox in patients with low- or intermediate-1-risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk.

Iron chelation therapy associated with improvement of hematopoiesis in transfusion-dependent patients.

BACKGROUND: It is well known that iron overload may cause multiple organ failure. In chronically transfused patients, optimal iron chelation therapy is associated with reduced morbidity and mortality. Furthermore, chelation therapy has been associated with erythroid responses. STUDY DESIGN AND METHODS: Among chronically transfused adults affected by myeloproliferative neoplasms and treated with iron chelators, two case reports are described. CASE REPORT: A male adult patient with myelodysplastic syndrome (MDS) and a female adult with aplastic anemia (AA), both transfusion-dependent, were treated with deferasirox, an oral iron chelator. RESULTS: A significant reduction in transfusion requirement was observed and was dependent on chelation therapy. The patient affected by AA also experienced a significant increase in hemoglobin levels. Minimal doses of deferasirox maintained the erythroid responses. Many mechanisms of action of the drug on erythropoiesis have been postulated. The early erythroid response seems to be independent of the removal of iron from deposits, per se, since the reduction of ferritin levels (a surrogate marker of iron deposits) below threshold levels occurs as a later event. CONCLUSION: Although there are few reports on erythroid responses in patients undergoing iron chelation therapy, they may give new insights in the pathogenesis of MDS and other myeloproliferative neoplasms. AA may benefit in terms of erythroid response. The findings in these cases underline the clinical importance of treating patients with iron overload. A survival benefit of chelation in patients with myeloproliferative neoplasms is still to be confirmed.