Vincristine toxicity with co-administration of fluconazole during induction therapy for pediatric acute lymphoblastic leukemia

Abstract

Background: Antifungal prophylaxis is recommended for patients with acute lymphoblastic leukemia (ALL) during high-risk periods such as induction; however, increased vincristine toxicities have been reported with the co-administration of triazole antifungals. We sought to determine whether vincristine-associated toxicities are higher among children with ALL concurrently given fluconazole prophylaxis compared to no prophylaxis.

Procedure: Using a retrospective cohort design, we reviewed records of pediatric patients treated for newly diagnosed ALL from 2003 to 2013. Patients were classified by fluconazole exposure during induction. The development of vincristine-associated toxicity and vincristine dose adjustment were the primary outcomes evaluated. The adjusted risk difference (RD) for vincristine-related toxicity associated with triazole exposure was determined.

Results: We identified 197 patients meeting inclusion criteria for evaluation, 160 (81%) of whom received fluconazole prophylaxis. Among patients receiving fluconazole, 36/160 (22%) developed vincristine toxicity compared to 7/37 (19%) among those not receiving prophylaxis (RD: 3%, 95% confidence interval [CI] -11 to 18%). Adjusting for patient age and race, no statistically significant increased risk for vincristine-associated toxicity with fluconazole exposure was observed (RD 5%, 95% CI -8 to 17%). An increased risk for vincristine-associated toxicity was independently associated with age 10 years or older (RD 19%, 95% CI 4-34%).

Conclusion: Co-administration of fluconazole during induction therapy for pediatric ALL does not significantly increase the risk for vincristine-associated toxicities; however, patients 10 years or older are at an increased risk for toxicity independent of fluconazole exposure. Prophylaxis with fluconazole during induction therapy for pediatric ALL, if warranted, appears to be a safe clinical practice.

Keywords: fluconazole; leukemia; pediatrics; vincristine.