Ototoxicity in hemoglobinopathy patients chelated with desferrioxamine

Purpose: Ototoxicity often limits the dose of desferrioxamine (DFO) tolerated by patients who are transfusion dependent. Current recommendations advise doses of < 50 mg/kg/day after early reports noted higher rates of ototoxicity with increasing doses. There have been no follow-up studies to determine the effect of this recommendation on ototoxicity and iron overload. Methods: We followed 28 patients who were chronically chelated with serial audiograms over a 5-year period. Patients with and without ototoxicity were compared with respect to age, disease, DFO dose, peak DFO dose, length of DFO therapy, ferritin, and therapeutic index. Results: Eight of the 28 patients (29%) had an abnormal audiogram during threshold testing. Two patients had two separate episodes with hearing deficit. Nine of the 10 episodes were high-frequency losses, with seven being moderate and three mild. All deficits were rapidly reversible with DFO dose reduction. No significant differences were found between the affected and unaffected groups with respect to age, DFO dose or duration, ferritin, or therapeutic index. Numbers of affected patients were small, but patients with SCD differed from patients with thalassemia in that they developed ototoxicity earlier and with lower doses of DFO and lower therapeutic indexes. Conclusions: Despite DFO doses usually felt to be low risk for ototoxicity, we found a high rate of ototoxicity in our patients who we've chronically chelated. No variables were identified that reliably predicted ototoxicity. We stress the need for regular audiological exams and feel no dose of DFO is ''safe'' from the development of ototoxicity.