Improved survival in thalassemia major patients on switching from desferrioxamine to combined chelation therapy with desferrioxamine and deferiprone

deaths) were from cardiac causes.Other causes of death were: infection 9 (14%), accident 6 (9%), other 6 (9%), not known 5 (8%), malignancy 4 (6%), liver disease 3 (5%).Within the Birth Cohort, 18 (6%) patients died, 7 from cardiac causes.Three-hundred and four (55.9%) patients switched to CCT and 269 (49.4%) continued for at least six months.Indications for switching were: high serum ferritin (66.6%), deteriorating left ventricular function on echocardiography or clinically (25.2%), low myocardial T2* (2.8%), and intolerable side effects of frequent DFO infusions (5.4%).Results of multivariable analysis are shown in Table 2.For CCT, the hazard ratio of 0.14 equates to 7.4-fold improved survival for each year on therapy.In the birth cohort, CCT was the only independent factor associated with survival.For cardiac deaths, the effect of CTT could not be calculated since there were no events in those initiated on therapy.Making an arbitrary assumption that the patient with the median duration of CCT had in fact died of a cardiac cause, CCT is associated with a 4-fold increased chance of survival from cardiac death.Seventy-five patients (24.7%) stopped CCT.This high incidence of discontinuations was consistent with most other long-term studies in CCT.[6][7][8][9] Reasons for stopping were: agranulocytosis (5%), recurrent neutropenia (2.9%), gastrointestinal disturbance (5.6%), non-compliance with DFO (3.3%), pregnancy (2.6%), arthralgia (1.6%), allergy (0.7%), weight gain (0.7%), increased liver enzymes (0.3%), other (2%).For those treated for at least six months, the median (standard deviation) therapy duration was 3.59 (1.96) years.There was one death in a patient during treatment with CCT.This was due to E. coli sepsis and was not associated with neutropenia or agranulocytosis.This study provides good evidence that CCT is effective in controlling body iron stores in moderately to heavily iron loaded patients and prevents iron overload related deaths.It is not clear whether equal benefits would be obtained with DFP monotherapy, as shown in another study, 10 or with the new oral iron chelating drug deferasirox, where the efficacy in terms of survival has not yet been established.We observed a high rate of discontinuations and of severe but manageable adverse events with CCT, highlighting the need for supervision from a specialist center.Management of the risk of agranulocytosis requires weekly full blood counts, and periodically reminding patients about this potential risk.