Breakthrough Invasive Fungal Infections in Patients with Acute Myeloid Leukemia

Abstract

Objectives: We sought to determine the occurrence, risk factors, effect of antifungal prophylaxis, and outcomes of invasive fungal infections (IFIs) in patients with acute myeloid leukemia (AML).

Patients and methods: We performed a retrospective analysis of all adult patients admitted to the University of Michigan Health System for AML over a 3-year period from 2010 to 2013. We determined comorbidities, hematopoietic cell transplant (HCT) status, antifungal prophylaxis, proven and probable IFI, and outcomes at 12 weeks after initiation of appropriate antifungal therapy.

Results: Of 333 patients in our cohort, 116 of whom had received a HCT, 98 (29%) developed an IFI. Of the 30 (9%) patients who had a proven or probable IFI, 18 had breakthrough infection while on micafungin (n = 5), voriconazole (n = 4), posaconazole (n = 5), or fluconazole (n = 4). Breakthrough IFIs were due to Aspergillus species (n = 11), other molds (n = 4), and Candida species (n = 3). Factors associated with breakthrough IFI were prolonged severe neutropenia (p = .05) and having received tacrolimus (p = .04). Antifungal therapy was successful in 7 of the 18 (39%) patients with breakthrough IFI and 8 of the 12 (67%) patients with non-breakthrough IFI, p = .13. Mortality at 12 weeks was 27%, 5 with breakthrough IFI and 3 with non-breakthrough IFI and was associated with prolonged severe neutropenia, p = .04.

Conclusions: Patients with AML remain at risk for IFI despite the use of several different antifungal agents for prophylaxis. Mortality remains high in patients with AML who develop IFI.

Keywords: Acute leukemia; Antifungal prophylaxis; Aspergillosis; Breakthrough invasive fungal infections; Mold infections.