Evaluation of antifungal prophylaxis in pediatric patients with acute lymphoblastic leukemia or acute myeloid leukemia

Abstract

Background

Invasive fungal disease (IFD) is a leading cause of morbidity and mortality in patients with hematologic malignancies. The most recent practice guidelines, last updated in 2020, recommend using a mold-active azole or echinocandin when antifungal prophylaxis is warranted; however, there has historically been a lack of standardized prescribing practices at our institution.

Objective

This study’s primary aim is to characterize our institution’s current prescribing patterns by comparing the incidence of IFD among pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with or without antifungal prophylaxis.

Methods

This single-center, retrospective chart review evaluated patients with ALL or AML treated at Arkansas Children’s Hospital from January 1, 2020, to August 31, 2023. Secondary analyses included evaluating IFD in high-risk patients, incidence of adverse events, and use of therapeutic drug monitoring. Descriptive statistics were calculated and statistical significance was determined using chi-square, Fisher’s exact, and Mann-Whitney U tests.

Results

A total of 114 patients were included, with 54 patients receiving antifungal prophylaxis. Patients receiving antifungal prophylaxis with fluconazole had a higher incidence of IFD than other prophylaxis agents and no prophylaxis (P < 0.01). Among high-risk patients, 62.9% received antifungal prophylaxis. There was a lower incidence of IFD in those who received mold-active prophylaxis than those who did not (17.4% vs. 35.1%, P = 0.03) and in those who received guideline-directed prophylaxis than those who received fluconazole prophylaxis (19.7% vs. 57.1%, P < 0.01).

Conclusions

We found considerable variability in prescribing practices at our institution, particularly among high-risk patients. In addition, patients who received fluconazole prophylaxis had a statistically significant higher incidence of fungal infections and elevated QTc than those who received other prophylaxis agents and no prophylaxis. Overall, this study highlights the importance of evaluating institutional practices and using guideline-based prophylaxis agents in children at high risk of IFD.