Influence of Antifungal Prophylaxis on Cyclophosphosphamide Based Regimen Transplant Outcomes

Cyclophosphamide is a chemotherapeutic agent that may be included in stem cell transplant preparative regimens. Cyclophosphamide is a pro-drug that is converted to cytotoxic metabolites via multiple pathways of the cytochrome P-450 enzyme system. The triazole antifungal agents may be prescribed as fungal prophylaxis for stem cell transplant patients. The triazole antifungals are inhibitors of some cytochrome P-450 pathways that are utilized for cyclophosphamide conversion. Due to this drug interaction, some transplant centers will substitute an alternate agent instead of a triazole antifungal during cyclophosphamide therapy. Adult data has demonstrated that there is no difference in the AUC of the phosphoramide metabolite when given with fluconazole. The goal of this review is to examine if antifungal drug interactions influence stem cell transplant survival or disease relapse. This is a single center, retrospective review of 5 years of transplant outcomes for pediatric and young adult patients diagnosed with a hematologic malignancy that underwent hematopoietic stem cell transplant and received cyclophosphamide as part of the transplant preparative regimen. Outcomes measured were survival, relapse or progressive disease and non-relapse mortality. The medical charts of 25 patients with diagnoses of AML, ALL, MDS and Lymphoma were reviewed. Outcomes were stratified for voriconazole, fluconazole and non-azole antifungal patients. Survival results were 50% for voriconazole, 64% for fluconazole and 33% for non-azole therapies. Relapse or progressive disease rates were 16% for voriconazole, 18% for fluconazole and 33% for non-azole therapies. Non-relapse mortality was 33% for voriconazole, 18% for fluconazole and 33% for non-azole therapies. For azole versus non-azole therapy relapse rates were 17% versus 33% respectively. In a small cohort of pediatric and young adult patients, the cytochrome P-450 interaction of azole antifungals and cyclophosphamide does not appear to influence transplant survival outcomes. Larger pediatric studies may be warranted to examine this clinical question.