Epidemiology of Invasive Fungal Diseases in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation Recipients Managed with an Antifungal Diagnostic Driven Approach.

Maria Daniela Bergamasco,Marcio Nucci,Fabio Kerbauy,Diogo B Ferreira,Celso Arrais-Rodrigues,Arnaldo Lopes Colombo,Carlos Alberto P Pereira,Otavio Baiocchi

doi:10.3390/jof7080588

Abstract

Patients with hematologic malignancies and hematopoietic cell transplant recipients (HCT) are at high risk for invasive fungal disease (IFD). The practice of antifungal prophylaxis with mold-active azoles has been challenged recently because of drug–drug interactions with novel targeted therapies. This is a retrospective, single-center cohort study of consecutive cases of proven or probable IFD, diagnosed between 2009 and 2019, in adult hematologic patients and HCT recipients managed with fluconazole prophylaxis and an antifungal diagnostic-driven approach for mold infection. During the study period, 94 cases of IFD occurred among 664 hematologic patients and 316 HCT recipients. The frequency among patients with allogeneic HCT, autologous HCT, acute leukemia and other hematologic malignancies was 8.9%, 1.6%, 17.3%, and 6.4%, respectively. Aspergillosis was the leading IFD (53.2%), followed by fusariosis (18.1%), candidiasis (10.6%), and cryptococcosis (8.5%). The overall 6-week mortality rate was 37.2%, and varied according to the host and the etiology of IFD, from 28% in aspergillosis to 52.9% in fusariosis. Although IFD occurred frequently in our cohort of patients managed with an antifungal diagnostic driven approach, mortality rates were comparable to other studies. In the face of challenges posed by the use of anti-mold prophylaxis, this strategy remains a reasonable alternative.

Highlights

Patients with hematologic malignancies are at high risk of developing invasive fungal disease (IFD)
The highest incidences have been reported in allogeneic hematopoietic cell transplant (HCT) recipients and in patients with acute myeloid leukemia (AML) receiving induction remission chemotherapy [1,2,3,4,5,6]
Recent studies have shown a high incidence of IFD in patients with acute lymphoid leukemia (ALL) [7,8], and the emergence of a new group at risk: patients with chronic lymphoproliferative diseases receiving ibrutinib [9,10,11]

Summary

Introduction

Patients with hematologic malignancies are at high risk of developing invasive fungal disease (IFD). Recent studies have shown a high incidence of IFD in patients with acute lymphoid leukemia (ALL) [7,8], and the emergence of a new group at risk: patients with chronic lymphoproliferative diseases receiving ibrutinib [9,10,11]. While the introduction of these targeted therapies represents a great advance in the field, with significant improvements in the outcome, the use of mold-active azoles as prophylaxis may be problematic because of drug–drug interactions. Both posaconazole and voriconazole are strong cytochrome P450 3A4 inhibitors [18,19], which is the main metabolic pathway of these targeted therapies [20]. We describe the epidemiology of IFD in patients with hematologic diseases treated at a single center in Brazil, managed with fluconazole prophylaxis and a diagnostic-driven antifungal approach for mold infections

Methods

Results

Discussion

Conclusion