Desferrioxamine ototoxicity in an adult transfusion-dependent population

The purpose of this study was to identify the incidence of hearing loss in a population of 75 adult (19-68 years old) transfusion-dependent patients with thalassemia major, sickle cell disease, Diamond-Blackfan anemia, and various other hematologic disorders treated with regular transfusion schedules. Ninety-three percent (70/75) of patients had a history of long-term subcutaneous or intravenous desferrioxamine therapy.

The patients underwent routine otolaryngologic history and physical examination, along with standard pure-tone audiometry at 250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz, with hearing loss defined as 25 dB or greater at one or more frequencies.

Hearing loss was present in 57% (43/75) of patients. More importantly, hearing loss attributable to desferrioxamine ototoxicity was present in 29% (22/75) of patients. Sixteen patients treated previously with desferrioxamine were switched to the experimental oral chelating agent, L1. Eight of these 16 patients had hearing loss attributable to desferrioxamine, with 5 of these patients worsening with the experimental oral chelating agent L1. Seventy-nine percent (59/75) of patients were thalassemic. Fifty-four percent (33/59) of these thalassemic patients had hearing loss. However, 35% (21/59) of the thalassemic patients had hearing loss attributable to desferrioxamine ototoxicity. All thalassemic patients with desferrioxamine ototoxicity had high-frequency sensorineural hearing loss, with 33% (7/21) having a notch at 6 kHz. In addition, 5% (1/21) had notching at 3 khz. Few of the hearing losses were disabling.

Management of these patients requires proper dosing of desferrioxamine and transfusion therapy, along with regular monitoring of body iron burden and hemoglobin. In addition, regular otolaryngologic and audiometric follow-up with special care to include the frequencies of 3 and 6 kHz may help recognize and prevent permanent ototoxicity.