Voriconazole as a Secondary Prophylaxis for Invasive Fungal Infections in Allogeneic Hematopoietic Stem Cell...

Voriconazole plays an important role in the treatment of invasive fungal infections (IFIs). Keeping voriconazole concentration at appropriate levels is crucial for drug effectiveness and safety. However, it remains unclear whether drug concentrations influence the clinical outcome of secondary prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT).

In this retrospective analysis, 83 patients receiving allo-HSCT with histories of IFIs responsive to voriconazole were enrolled. These patients continued voriconazole during and after allo-HSCT. Their characteristics, clinical outcomes, and plasma voriconazole concentrations at (1) Days -30 to -9, (2) Days -8 to -1, (3) Days 0 to 14, and (4) Days 15 to 30 of allo-HSCT were examined.

Voriconazole trough concentrations significantly declined after transplantation and remained low for approximately 4 weeks post allo-HSCT, despite dose adjustment. This variation was observed across subgroups defined by age, sex, diagnosis, conditioning regimens, donor type, administration route, or documented drug interactions. The cumulative incidence of breakthrough IFI was 11.4% at 3 months and 18.6% at 1 year after transplantation. Transient decreases in voriconazole trough levels were not significantly associated with breakthrough IFIs. However, a trend toward a lower risk of proven or probable breakthrough IFIs at 12 months has been observed in patients having average voriconazole trough levels ≥ 1 mg/L after allo-HSCT.

Transient fluctuations in voriconazole levels occur after allo-HSCT, independent of most clinical factors. These subtherapeutic exposures did not significantly affect the incidence of breakthrough IFIs in this cohort. Larger prospective studies are warranted to further investigate the clinical impact.