Voriconazole provides effective prophylaxis for invasive fungal infection in patients receiving glucocorticoid therapy for GVHD

Abstract

Patients on systemic glucocorticoids for graft-versus-host disease (GVHD) after hematopoietic cell transplant are susceptible to invasive fungal infections (IFI), which greatly contribute to morbidity and mortality. We evaluated the efficacy of prophylactic treatment options (voriconazole versus fluconazole or itraconazole) for IFI by performing a retrospective review of patients on glucocorticoids for GVHD given voriconazole (n = 97), fluconazole (n = 36), or itraconazole (n = 36). IFI developed in 7/72 (10%) patients on fluconazole/itraconazole versus 2/97 (2%) on voriconazole (P = 0.03) within the first 100 days of glucocorticoids. Five patients developed Aspergillus IFI on fluconazole/itraconazole (7%), compared to none on voriconazole (0%) (P = 0.008); Aspergillus IFI resulted in death in all 5 patients. We found that IFI occurred in patients who received an initial dose of at least 2 mg/kg/day of prednisone or equivalent; when the analysis was restricted to these patients, the hazard ratio (0.39; 95% confidence interval: 0.08–1.86) was consistent with a protective effect of voriconazole compared with fluconazole/itraconazole, although this subset analysis did not reach significance. Overall survival at 100 days after start of glucocorticoids was 77% in patients given fluconazole/itraconazole and 85% in those given voriconazole (P = 0.22). Our results suggest that voriconazole is more effective than fluconazole/itraconazole in preventing IFI, especially aspergillosis, in patients receiving glucocorticoids posttransplant.

Invasive Candidiasis in the Neutropenic Cancer Patient

“…However, patients with GvHD involving the gastrointestinal tract were not well represented in this study, as they may not be able to take oral agents, and posaconazole is available only in oral suspension. Another retrospective study among patients receiving systemic glucocorticoids for GvHD after HSCT showed that voriconazole was more effective than fluconazole/itraconazole in preventing IC [42].…”

Antifungal prophylaxis during treatment for haematological malignancies: are we there yet?

“…Recently, one centre has reviewed their experience with voriconazole administered either orally or intravenously to allogeneic HSCT recipients receiving at least 1 mg/kg/d of prednisolone for GVHD and reported only two Candida spp infections in 97 patients (Gergis et al , 2009). GVHD was initially graded as grade 3–4 in 31% of these patients.…”

High-Risk Myelodysplastic Syndromes: Chemotherapy, Transplantation, and Beyond

“…Posttransplant hypomethylation is an evolving concept; it does not seem to affect chimerism or GVHD (compared with DLI). The advent of low-intensity conditioning, highresolution HLA typing, and improved supportive care have resulted in a marked decrease in NRM [50,51]. Nevertheless, relapse rates are still high, at a rate of 25% to 50%.…”