Neurotoxicity of Bfm-95 on the Medial Olivocochlear Bundle Assessed by Means of Contralateral Suppression of 2f1-f2 Distortion Product Otoacoustic Emissions

Objective: Berlin-Frankfurt-Munster 95 (BFM-95) is a common chemotherapeutic protocol against acute lymphoblastic leukemia (ALL). This prospective study investigates whether this protocol has an adverse effect on the medial olivocochlear bundle (MOCB) and/or outer hair cells' (OHCs) function. The distortion product otoacoustic emissions (DPOAEs) and their suppression by means of contralateral application of white noise were used for assessing the function of OHCs and the MOCB, respectively. Study Design: Prospective study. Setting: Oncology and otorhinolaryngology departments in a pediatric hospital. Patients: Thirty-six children treated with ALL-BFM-95. Interventions: Before chemotherapy, a baseline audiologic evaluation with tympanogram, standard and extended high frequency, pure-tone audiometry, and DPOAEs in the absence and presence of white noise was performed in all children. This population was divided in three groups. In a first group (n = 12), the evaluation was repeated after four sessions of vincristine administration; in the second group (n = 12), after 8 sessions; and in the third group (n = 12), several months after completion of the protocol. Main Outcome Measure: DPOAEs suppression by contralateral application of white noise. Results: In the first and the third groups, we observed no changes in DPOAE amplitudes. Nevertheless, in the second group, the DPOAEs demonstrated significant decrease at 1416, 1685, 2002, and 2380 Hz. At baseline examination, all groups presented significant suppression at all frequencies. After eight vincristine sessions, instead of suppression, an increase of amplitudes was noted at 5 of 12 frequencies. Efferent-mediated DPOAE suppression reappeared in the third group at all frequencies (significant at 5 of 12 frequencies). Conclusion: ALL-BFM-95 seems to exert an early and reversible toxic effect on the MOCB, whereas its effects on OHCs are minimal and reversible. These minimal cochleotoxic and neurotoxic properties of ALL-BFM-95 might prove useful for research studies on the role of efferent innervation in hearing.