Combination antifungal treatment for invasive fungal disease after hematopoietic stem cell transplantation in children with hematological disorders

摘要

Abstract Background Invasive fungal disease (IFD) has a poor prognosis in children with hematological disorders after hematopoietic stem cell transplantation (HSCT). We assessed if drug combinations with different targets may improve the outcome. Methods Retrospective study to assess the outcome of combination antifungal therapy (CAT) for proven‐probable IFD (PP‐IFD) in children with hematological disorders after HSCT from January 2008 to June 2018. Results Over the 10‐year period, 95 PP‐IFD were diagnosed in pediatric recipients, median age of 5.6?years. Twenty‐seven patients received combinations of caspofungin and voriconazole, 28 patients received combinations of caspofungin and amphotericin B, and 40 patients received combinations of voriconazole and amphotericin B. The overall response rate of PP‐IFD was 77.9%, while the 100‐day overall survival rates were 66.8%. Univariate analysis showed that factors that significantly affected the response to combination treatments were type of combination ( P ?=?0.02), the stem cell source ( P ?=?0.04), the donor type ( P ?=?0.03), HLA‐match ( P ?=?0.03), aGVHD ( P ?=?0.02), period of treatment ( P ?=?0.044), use of corticosteroids (0.036), CD4:CD8 ratio ( P ?=?0.014), and CMV viremia ( P ?=?0.033). In addition, multivariate analysis demonstrated that only the type of combination remained a significant factor (odds ratio?=?0.335, 95% confidence interval: 0.071‐0.812, P ?=?0.042). Forty‐three children suffered from mild and reversible adverse reactions, no serious side effects during treatment. Conclusion A variety of factors can affect the outcome of CAT. Combination of caspofungin with voriconazole is a safe and helpful treatment option for HSCT recipients with IFD.