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. CONCLUSION: 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.

Neurotoxicity of vincristine on the medial olivocochlear bundle.

OBJECTIVE: Vincristine is a well known neurotoxic chemotherapeutic agent. Dose dependent and cumulative peripheral neuropathy is the main dose limiting side effect of chemotherapy with vincristine. The mechanisms responsible for the neurotoxic effects of vincristine have not yet been fully understood. This prospective study was directed at determining whether vincristine treatment interferes with the function of the medial olivocochlear bundle. DESIGN: Fifteen children suffering from leukemia were subjected to tympanogram, stapedial muscle reflex, pure tone audiometry and transient evoked otoacoustic emissions (TEOAEs) in the absence and presence of contralateral white noise on day 1 and on day 22 of treatment with vincristine. The function of the medial olivocochlear bundle was assessed by the phenomenon of suppression of otoacoustic emissions by contralateral application of white noise. RESULTS: The study revealed a statistically significant decrease of contralateral suppression amplitudes in all cases after three sessions of chemotherapy with vincristine. On the contrary no alterations were observed in pure tone audiometry thresholds. A non-significant decrease of the mean TEOAEs' amplitudes was also noted. When analyzed by frequency, however, this decrease reached the level of statistical significance at two frequencies. CONCLUSION: Vincristine treatment seems to exert a neurotoxic effect on the efferent olivocochlear system, which takes place early in the course of chemotherapy. This is a new aspect to be added to the possible mechanisms underlying the toxicity of vincristine in the auditory periphery. Whether changes in efferent function might contribute to understanding the mechanisms of neurotoxicity caused by vincristine, or find any clinical application as a predictor or early detector of neurological side effects of vincristine still remains to be seen.

The effect of treatment with vincristine on transient evoked and distortion product otoacoustic emissions.

OBJECTIVE: Vincristine chemotherapy is mainly associated with neurotoxic effects. The ototoxicity of vincristine has been related to high dosage, while low and moderate doses do not seem to induce significant hearing impairment when measured by pure tone or speech audiometry. Otoacoustic emissions have been reported to be more sensitive in early detection of ototoxicity than conventional pure tone audiometry. The present study was directed at determining whether vincristine treatment interferes with outer hair cell function in the absence of measurable changes in pure tone audiometry. METHODS: We studied prospectively a cohort of ten children suffering from leukemia. All children were subjected to tympanogram, stapedial muscle reflex, pure tone audiometry, transient evoked (TEOAEs) and distortion product (DPOAEs) otoacoustic emissions on day 1 and on day 22 of treatment with vincristine. TEOAEs were analyzed in terms of emission level and reproducibility as a function of frequency. DPOAEs were obtained as DP-grams and were analyzed in terms of amplitude. RESULTS: The analyzed parameters of TEOAEs and DPOAEs revealed a declining tendency, although changes did not reach statistical significance. Pure tone audiometry and stapedial reflex thresholds were not altered. CONCLUSION: For the population of this study, vincristine did not seem to cause significant alterations of otoacoustic emissions' recordings and consequently significant outer hair cell damage.