971. Breakthrough Invasive Fungal Infections (IFI) in Acute Leukemia (AL) Patients Receiving Antifungal Prophylaxis

Abstract

BackgroundA major challenge in patients with AL receiving chemotherapy is to decrease the risk of IFI during the prolonged neutropenic period. Even with antifungal prophylaxis, the incidence of breakthrough IFI can be as high as 14%. Our objectives were to determine the incidence of all IFI and breakthrough IFI, to define risk factors associated with IFI, and to assess outcomes.MethodsSingle-center retrospective cohort analysis of all adult patients admitted to the University of Michigan for AL from January 1, 2010 to December 31, 2013. Chart review determined co-morbidities, chemotherapy regimens, antifungal prophylaxis, occurrence of IFI as determined by EORTC/MSG criteria, and outcomes. Chi-square, Fischer’s, ANOVA, and binary logistic regression tests were performed when appropriate.ResultsOf 363 patients, all but 4 had acute myeloid leukemia (AML); 124 had a stem cell transplant (SCT). A total of 103 (28%) had proven (n = 13), probable (n = 22), or possible (n = 68) IFI. Considering only those 35 patients who had proven or probable IFI, the only risk factor for development of IFI by logistic regression analysis was IFLAG chemotherapy (P = .006). Mold infections occurred in 27 patients: Aspergillus (19), Mucorales (5), both Aspergillus and Mucorales (1), Alternaria (1), and Scedosporium (1). Additionally, 5 patients had invasive candidiasis and 3 had Pneumocystis. Eighteen of 35 patients (51%) had breakthrough IFI while on posaconazole suspension (6), fluconazole (5), micafungin (5) or voriconazole (2). Factors significantly associated with breakthrough IFI were SCT (P = .04), neutrophils <500, ≥10 days at diagnosis (P = .002) and prophylaxis with posaconazole suspension (P = .003). Twelve-week mortality in proven and probable IFI was 31% (11/35). Nine of 11 deceased patients had breakthrough IFI; 8 of whom (5 with mold IFI and 3 with invasive candidiasis) died of the fungal infection.ConclusionPatients receiving chemotherapy for AL remain at risk for IFI despite the the use of antifungal prophylaxis. In our study, prophylaxis with posaconazole suspension was found to be an independent risk factor for breakthrough IFI. Mortality was high among patients with breakthrough IFI.Disclosures All authors: No reported disclosures.