Ototoxicity in Pediatric Hematopoietic Stem Cell Transplantation With High‐Dose Carboplatin: Identifying Modifiable Risk Factors Through the Inclusion of Younger Patients

BACKGROUND: Carboplatin ototoxicity is observed when used in high doses. We investigated risk factors associated with ototoxicity in high-dose carboplatin hematopoietic stem cell transplantation (cHSCT) in a pediatric population. METHODS: We completed a retrospective analysis of medical and audiologic records for patients who underwent autologous cHSCT from January 1, 2008 to June 30, 2022. We accepted audiograms with a minimum requirement of threshold data at 4 kHz in at least one ear, allowing us to assess younger, more difficult to test patients and focus on hearing losses at important speech frequencies. Three audiologic outcome measures were evaluated-worsening in SIOP grade, significant change in hearing, and ototoxicity for audiograms with data up to 4 kHz and data up 8 kHz. RESULTS: Forty-three cHSCTs from 29 patients had sufficient audiologic data. Ototoxicity was observed in 49% of the data up to 4 kHz and in 78% of the data up to 8 kHz. Cumulative dose of prior cisplatin (OR = 1.01, 95% CI = 1.002-1.014, p = 0.011) and cumulative dose of carboplatin in the preparative regimen (OR = 1.003, 95% CI = 1.001-1.004, p = 0.001), were associated with ototoxicity. Concurrent furosemide with carboplatin administration resulted in 100% ototoxicity, with patients demonstrating a mean change in SIOP grades by 2.0 SE ± 0.038. CONCLUSION: Using criterion that allowed for the evaluation of very young children, this report demonstrates that cumulative dose of prior cisplatin, cumulative dose of carboplatin in the preparative regimen, and concomitant furosemide administration with carboplatin is associated with ototoxicity in cHSCT.