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

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Presenting Author(s)

Anastasia Wasylyshyn

Infectious Disease Fellow
University of Michigan
Ann Arbor, MI
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

KL

Kathleen A. Linder

Assistant Professor/Hospital Epidemiologist
Ann Arbor VAMC
Ann Arbor, Michigan
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Stephen M. Maurer

Infectious Disease Fellow
University of Michigan Hospitals
Ann Arbor, Michigan
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
VS

Virginia Sheffield

Chief Resident
University of Michigan
Ann Arbor, Michigan
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
LB

Lydia Benitez Colon

Adjunct clinical instructor in Pharmacy
University of Michigan
Ann Arbor, Michigan
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CK

Carol A. Kauffman

Professor
University of Michigan, Ann Arbor VA Healthcare System
Ann Arbor, Michigan
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Marisa H. Miceli

Associate Professor
University of Michigan
Ann Arbor, Michigan
Disclosure: SCYNEXIS, Inc. (Advisor or Review Panel member)

Background: Despite 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.

Methods: This 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.

Results: Of 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.

Conclusion: Patients 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.