Audiologic assessment of beta-thalassemia major children under combined versus single agent chelation therapy

ABSTRACT

Beta-thalassemia major [BTM] is an inherited blood disorder which leads to life threatening anaemia and requires regular blood transfusions andironchelating therapy throughout life from early childhood. Parenteral chelation therapy with desferrioxamine [DFO] is well established, however, poor compliance with the rigours of parenteral treatment limits its regular use. The orally active iron chelator deferiprone [LI] has been shown to be as effective as DFO in some patients. The improvement of iron status resulting from the combined use of both LI and DFO due to [he additive effects of both drugs and the lack of toxicity caused by combining the drugs, however, suggest that this is a promising new method of iron chelation. This study was undertaken to assess the audiologic test results of combined [LI and DFO] therapy versus single agent [LI or DFO] therapy for reducing transfusional iron overload, and to evaluate the safety of the oral chelator Deferiprone [LI] on the auditory system. Sixty six beta thalassemia major children were included in this study. They were randomly classified into 3 arms Patients in arm A were under combined DFO and LI chelation therapy. Patients in arm B were under LI therapy and patients in arm C were under DFO therapy. All patients were subjected to full history taking and laboratory investigations. Audiologic evaluation was performed at the beginning of the study [baseline evaluation] and at the 1 year follow-up [termination of the study] and consisted of puretone audiometry [PTA], extended high frequency audiometry, unmittance metry, otoacoustic emission [OAE]; transient evoked OAE [TEOAE] and distortion product OAE [DPOAE] and Auditory brainstem response [ABR]. Patients in arms A and B exhibited an improvement in their PTA and OAE results at the 1 year follow-up period. While patients in arm C presented with deterioration 11 their hearing sensitivity and cochlear function especially it the high frequencies. There was no association between hearing loss, serum ferritin level, age and Hb level. Patients under combined therapy exhibited slightly higher [better] TEOAE and DPOAE results than patients under LI therapy although this did not reach statistical significance. ABR results revealed no significant difference between the 3 arms in the absolute and interpeak latencies of waves I, III and V at the 1 year follow-up period. DFO ototoxicity is more cochlear than ret-rocochlear and is more pronounced at the base of the cochlea and appears to be reversible if diagnosed early. DFO ototoxicity appears to be subject to individual susceptibility. Combined [DFO and LI] therapy and LI chelation therapy preserve cochlear and retrocochlear function. However, combined therapy proved to be slightly superior to LI therapy in preservation of cochlear function in addition to its superior chelating ability. It is recommended that thalassemic patients [especially those under DFO therapy] should undergo regular audiologic assessments by OAEs and should revert to combined [DFO and LI] therapy if cochlear impairment is detected. Deferiprone [LI] appears to be safe on the auditory system,however, its long-term effect still needs to be explored