1150. Breakthrough Invasive Fungal Disease (IFD) in Patients with Acute Myeloid Leukemia (AML)

Abstract

BackgroundDespite the use of antifungal prophylaxis, IFD remains a serious complication of AML causing extensive morbidity and mortality. This study seeks to clarify our experience with breakthrough infections in patients with AML.MethodsThis retrospective study included all adult patients undergoing induction chemotherapy for a new diagnosis of AML from June 2014 – Dec 2019 at the University of Michigan Hospital. Chart review determined co-morbidities, chemotherapy regimens, allogeneic hematopoietic cell transplant (HCT), antifungal prophylaxis, development of IFD, and outcomes. Patients were followed for 1 year from first induction chemotherapy. EORTC-MSGERC definitions for proven, probable, and possible IFD were used, as were MSGERC-ECMM definitions for breakthrough IFD.ResultsOf 251 patients, mean age was 61.8±14 years, 55% were men, and 73 (29%) underwent allogeneic HCT, 52 of whom developed GVHD. Thirty-one patients developed 33 IFD (12.3%): 4 proven, 12 probable, and 17 possible IFD. Four IFD occurred in patients with GVHD post-HCT; all were treated with high dose steroids and one received an anti-TNF agent. Of the 16 proven and probable IFD, 8 were breakthrough IFD. Mucormycosis occurred in 2 patients on voriconazole; fusariosis occurred in 3 patients taking fluconazole (2), or posaconazole (1). Aspergillosis occurred in 2 patients taking isavuconazole (1) or fluconazole (1), and pneumocystosis occurred in a patient receiving inhaled pentamidine. There were 8 non-breakthrough IFD, including 2 pneumocystosis, 4 aspergillosis, and 2 candidiasis. Risk for IFD increased with subsequent episodes of induction chemotherapy, p=.04.Six of 8 patients with breakthrough IFD and 5 of 8 without breakthrough IFD died within 12 weeks of IFD diagnosis. Excluding the 15 patients who had only possible IFD, 69% (11/16) patients with proven/probable IFD died compared with 35% (77/220) patients without IFD, p=.01.ConclusionPatients with AML remain at risk for fatal IFD despite the use of antifungal prophylaxis. Failure of prophylaxis in our patients who developed breakthrough IFD was associated with a shift towards less common fungi.Disclosures All Authors: No reported disclosures