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

doi:doi:10.1038/bmt.2009.210

Bone Marrow Transplantation advance online publication 17 August 2009; doi: 10.1038/bmt.2009.210

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

U Gergis¹, K Markey², J Greene³, M Kharfan-Dabaja³, T Field³, G Wetzstein², M J Schell⁴, Y Huang⁴, C Anasetti³ and J Perkins³

¹Department of Medicine, Weill Cornell Medical College, New York, NY, USA
²Department of Pharmacy, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
³Division of Blood and Marrow Transplant, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
⁴Biostatistics Core, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

Correspondence: Dr J Perkins, Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, FOB-3; BMT, Tampa, FL 33612, USA. E-mail: Janelle.perkins@moffitt.org

Received 21 April 2009; Revised 25 May 2009; Accepted 19 June 2009; Published online 17 August 2009.

Top

Abstract

Patients on systemic glucocorticoids for 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 or fluconazole vs itraconazole) for IFI by performing a retrospective review of patients on glucocorticoids for GVHD who were administered voriconazole (n=97), fluconazole (n=36) or itraconazole (n=36). IFI developed in 7/72 (10%) patients on fluconazole/itraconazole vs 2/97 (2%) on voriconazole (P=0.03) within the first 100 days of glucocorticoids. Five (7%) patients developed Aspergillus IFI on fluconazole/itraconazole, compared with none on voriconazole (0%) (P=0.008); Aspergillus IFI resulted in death in all five 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. OS at 100 days after start of glucocorticoids was 77% in patients administered fluconazole/itraconazole and 85% in those administered voriconazole (P=0.22). Our results suggest that voriconazole is more effective than fluconazole/itraconazole in preventing IFI, especially aspergillosis, in patients receiving glucocorticoids post transplant.