Long-term effects of chemotherapy for acute lymphoblastic leukemia on the medial olivocochlear bundle: effects of different cumulative doses of gentamicin.
OBJECTIVE
The treatment of acute lymphoblastic leukemia (ALL) often combines a neurotoxic chemotherapeutic protocol such as Berlin-Frankfurt-Munster-95 (BFM-95) with gentamicin, an antibiotic known to have an early and quickly reversed impact on olivocochlear reflex in animal studies. This study investigates whether this combination has any long-term side effects on the medial olivocochlear bundle (MOCB).


METHODS
In all 47 children of the study suppression of distortion product otoacoustic emissions (DPOAEs) by contralateral application of white noise (WN) was used to assess the function of the MOCB. The population was divided into three groups depending on the time interval between the end of therapy and examination. The group examined shortly after chemotherapy included 12 children who had received low gentamicin doses (less than 13 days). The group evaluated 2 years after therapy involved another 12 children who had required medium gentamicin doses (more than 13, less than 23 days). The group examined 3 years after therapy included a subgroup of 12 children to whom low gentamicin doses were infused and another 11 children with high gentamicin doses (more than 23 days).


RESULTS
Three years after therapy the olivocochlear reflex was efficiently produced in both subgroups of low and high gentamicin doses. Two years after therapy, contralateral WN induced increase of DPOAEs at 4 of the 12 examined frequencies. Shortly after therapy, WN increased, instead of suppressing, DPOAEs at five frequencies.


CONCLUSIONS
This abnormal result of contralateral noise application perceived as impaired cochlear efferent innervation may indicate that ALL-BFM-95 exerts a toxic effect on the MOCB, which is slowly reversed within the first 3 years after chemotherapy and does not seem to be affected in the long term by different cumulative doses of gentamicin.
Riga
M
M
ENT Department, University of Athens, Hippokration Hospital of Athens, 114 Vas. Sofias Avenue, GR-11528 Athens, Greece. mariariga@hotmail.com
Korres
S
S
Varvutsi
M
M
Kosmidis
H
H
Douniadakis
D
D
Psarommatis
I
I
Yiotakis
I
I
Ferekidis
E
E
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002648:Child; D003056:Cochlear Nerve / Q000187:drug effects* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects*; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects*; D006801:Humans; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects*; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D005839:Gentamicins