Long-Term Outcome of Deferasirox Chelation in Patients with Thalassemia Major

Introduction: Iron overload is one of themajor complicationsof transfusion treatment in patient with thalassemia major. Deferasirox is a once-daily orally active iron chelator and long-term efficacy and safety data are being published. Herein we report the long-term follow-up data of thalassemia major patients in a single center.

Methods: Of the 67 patients with thalassemia major who were under follow-up in a single center, 42 who were on deferasirox chelation for at least three years were included in the study. Patients' initial serum ferritin, ALT, creatinine, cardiac T2* and hepatic T2* values were recorded at the time of deferasirox initiation and at last visit. Deferasirox was not initiated as an iron chelator to none of the patients with a cardiac T2* value below 8 ms. All of the patients had creatinine clearance above 40 ml/minute and had serum creatinine levels within age appropriate normals at deferasirox initiation. None of the patients received any other chelations during the follow-up period.

Results: Mean age of the patients were 16±9.4 years (2-33.4 years) at initiation of deferasirox and 22 (52%) were females. Eighteen (43%) of the patients were splenectomized. Median follow-up time of deferasirox chelation was 7.9 years (3-10). The median deferasirox doses at initiation of chelation and at last visit were 20.5 mg/kg/day and 30.7 mg/kg/day (7-40), respectively. Serum ferritin levels decreased significantly with deferasirox chelation (median 1969 ng/ml (516-5404) vs 1113 ng/ml (339-4003), p<0,001). We did not find statistically significant difference between the inital cardiac T2* values and the values at the last visit (median 25 .3 ms((8.7-42) vs 32 ms (6.6-42), p=0.607), despite a dramatic increase. On the other hand, hepatic T2* values did not significantly change compared to initial values, as well (median 3.7 ms (1-13.6) vs 3.3 (1-16), p=0.865). However of the patients who had cardiac T2* value between 10-20 ms, 67% was found to have T2* value above 20 ms by the end of the follow-up duration. On the other hand 53% of the patients with hepatic T2* value below 3.5 ms, had T2* values above 3.5 ms by the end of the follow-up, indicating improvement in iron stores. None of the patients exibited an adverse event that requires cessation of the drug totally, but patients exibited transient hypertransaminasemia that required transient cessation and/or dose decrement. The changes in serum ALT and serum creatinine levels at the initiation and at last visit were not significant.

Conclusions: This is a a study that includes patients with a relatively long duration of follow-up. Although the cardiac T2* values improved by the end of the follow-up, this change was not found statistically significant. This can be attributed to the sample size and in a larger sample size, the change might be found significant. Additionally, the patients included in the study were composed of not only naive patients to chelation but also of the patients who were imcomplant to previous chelation and who were highly iron loaded before initiation of deferasirox.