Comparative study of liposomal amphotericin B, posaconazole, and micafungin for primary antifungal prophylaxis in pediatric patients with acute leukemia

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Abstract
Purpose: Invasive fungal diseases (IFDs) are a significant cause of morbidity and mortality in pediatric patients with hematologic malignancies including acute leukemia. Our study aimed to compare the efficacy of liposomal amphotericin B (L-AMB), posaconazole or micafungin as primary antifungal prophylaxis (PAP) in pediatric patients with acute leukemia. Methods: This retrospective observational study enrolled 95 pediatric patients with acute lymphoblastic leukemia (n = 70) or acute myeloid leukemia (n = 25), undergoing chemotherapy, including those undergoing allogeneic hematopoietic stem cell transplantation at the Department of Pediatrics, Jena University Hospital, Jena, Germany. PAP regimens included L-AMB (1 mg/kg/day or 3 mg/kg twice weekly, intravenously), posaconazole (100–300 mg/day, according to blood concentration, orally or intravenously) and micafungin (1 mg/kg/day or 3 mg/kg twice weekly, intravenously). Thirty-four patients (35.8%) received L-AMB, 37 patients (38.9%) received posaconazole, and 24 patients (25.3%) received micafungin. Patients with a history of IFD or concurrent or changing PAP were excluded. The primary endpoint was the occurrence of breakthrough IFD, while secondary endpoint included IFD-free survival. Statistical analyses were performed using Kaplan–Meier survival analysis, Gray’s test and Cox regression to evaluate IFD-free survival. Results: The overall incidence of IFD was 14.7% (14 of 95 patients). IFD developed in 10 of 33 patients (29.4%) receiving L-AMB, in 4 of 38 (10.8%) patients receiving posaconazole and in none of the patients receiving micafungin. IFD-free survival was 70.6% in the L-AMB group, 89.2% in the posaconazole group and 100% in the micafungin group (p = 0.005, log-rank test). Significant differences were also observed in the cumulative incidences of breakthrough IFDs (p = 0.006) assessed by Gray’s test. In multivariate Cox analysis, dichotomized prophylaxis regimes (posaconazole or micafungin vs. L-AMB) were independently associated with a reduced risk of IFD (HR = 0.244; 95% CI 0.076–0.777; p = 0.017). Age ≥ 10 years predicted inferior IFD-free survival (HR = 3.665; 95% CI 1.224–10.980; p = 0.020). Conclusion: We found a significant difference in efficacy between the three antifungal prophylaxis regimens. In our study, micafungin achieved the lowest IFD breakthrough rate. However, multicenter clinical studies would be needed to confirm the results.
Funding Information
  • Universitätsklinikum Jena

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