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.


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.
Riga
Maria
M
ENT Department, University Hospital of Patras, Patras, Greece. mariariga@hotmail.com
Korres
Stavros
S
Psarommatis
Ioannis
I
Varvutsi
Maria
M
Giotakis
Ioannis
I
Papadas
Theodoros
T
Ferekidis
Eleftherios
E
Apostolopoulos
Nikolaos
N
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
D000970:Antineoplastic Agents; D005839:Gentamicins; D014750:Vincristine