Invasive Fungal Disease in Patients with Newly Diagnosed Acute Myeloid Leukemia.

Anastasia I Wasylyshyn,Marisa H Miceli,Stephen M Maurer,Virginia M Sheffield,Carol A Kauffman,Blair J Richards,Kathleen A Linder,Lydia Benitez Colon

doi:10.3390/jof7090761

Abstract

This single-center retrospective study of invasive fungal disease (IFD) enrolled 251 adult patients undergoing induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) from 2014–2019. Patients had primary AML (n = 148, 59%); antecedent myelodysplastic syndrome (n = 76, 30%), or secondary AML (n = 27, 11%). Seventy-five patients (30%) received an allogeneic hematopoietic cell transplant within the first year after induction chemotherapy. Proven/probable IFD occurred in 17 patients (7%). Twelve of the 17 (71%) were mold infections, including aspergillosis (n = 6), fusariosis (n = 3), and mucomycosis (n = 3). Eight breakthrough IFD (B-IFD), seven of which were due to molds, occurred in patients taking antifungal prophylaxis. Patients with proven/probable IFD had a significantly greater number of cumulative neutropenic days than those without an IFD, HR = 1.038 (95% CI 1.018–1.059), p = 0.0001. By cause-specific proportional hazards regression, the risk for IFD increased by 3.8% for each day of neutropenia per 100 days of follow up. Relapsed/refractory AML significantly increased the risk for IFD, HR = 7.562 (2.585–22.123), p = 0.0002, and Kaplan-Meier analysis showed significantly higher mortality at 1 year in patients who developed a proven/probable IFD, p = 0.02. IFD remains an important problem among patients with AML despite the use of antifungal prophylaxis, and development of IFD is associated with increased mortality in these patients.

Highlights

All adult patients at least 18 years of age who had newly diagnosed acute myeloid leukemia (AML) and who were admitted for induction chemotherapy between June 2014 and January 2019 were screened for eligibility
Most patients had primary AML (n = 148, 59%); AML related to antecedent myelodysplastic syndrome (MDS) was present in 76 (30%) patients, and 27 (11%) had secondary AML related to treatment for a prior malignancy
Mold infections accounted for 71% of proven and probable invasive fungal disease (IFD), with Aspergillus the predominant organism, similar to prior reports [1,10]

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Invasive fungal disease (IFD) is a highly morbid complication in patients with hematologic malignancies, including acute myeloid leukemia (AML) [1]. Prior studies have demonstrated a benefit of mold-active antifungal agents for IFD prophylaxis in patients at high risk [2,3]. With widespread use of prophylaxis, breakthrough IFD (B-IFD) have become an increasing problem and have been reported in up to 18% of patients with. AML [4,5,6,7,8,9,10]. Studies suggested that the risk factors predisposing AML patients for

Methods

Results

Conclusion