title: Neurotoxicity of BFM-95 on the medial olivocochlear bundle assessed by means of contralateral suppression of 2f1-f2 distortion product otoacoustic emissions.
abstract: 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.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Oncology and otorhinolaryngology departments in a pediatric hospital.
  
  
  METHODS
  Thirty-six children treated with ALL-BFM-95.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: ENT Department, University Hospital of Patras, Patras, Greece. mariariga@hotmail.com
authors.forename: Maria
authors.initials: M
authors.lastname: Riga
authors.forename: Stavros
authors.initials: S
authors.lastname: Korres
authors.forename: Ioannis
authors.initials: I
authors.lastname: Psarommatis
authors.forename: Maria
authors.initials: M
authors.lastname: Varvutsi
authors.forename: Ioannis
authors.initials: I
authors.lastname: Giotakis
authors.forename: Theodoros
authors.initials: T
authors.lastname: Papadas
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Ferekidis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Apostolopoulos
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001301:Audiometry, Pure-Tone / Q000379:methods; D001306:Auditory Pathways / Q000187:drug effects*; D002648:Child; D015331:Cohort Studies; D005839:Gentamicins / Q000009:adverse effects; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D007262:Infusions, Intravenous; D009847:Olivary Nucleus / Q000187:drug effects* / Q000503:physiopathology*; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D011446:Prospective Studies; D012720:Severity of Illness Index; D014750:Vincristine / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D005839:Gentamicins; D014750:Vincristine