PI-06. Invasive aspergillosis caused by Aspergillus non-fumigatus in haematological patients

Summary

Introduction

Invasive aspergillosis (IA) is a major cause of morbidity in hematological patients. Aspergillus fumigates is the most common etiologic agent of IA reported in severely immunocompromised patients. Aspergillosis caused by non-fumigatus Aspergillus species is poorly studied.

Patients and methods

We designed the retrospective study in order to investigate the epidemiology of IA caused by Aspergillus non-fumigatus, as a single pathogen, in large cohort of patients after HSCT and chemotherapy from 2013 to 2018 at the R. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation (CIC725). During the observation period, 30 patients with IA caused by Aspergillus non-fumigatus were identified and included into analysis. According to EORTC/MSG 2008 criteria, one proven and 29 probable cases were diagnosed in children and adults with hematological malignances and non-malignant hematological diseases after allo-HSCT (n=27) and chemotherapy (n=3). The median age was 26 (3-60) years old (males, 53%). The median follow-up time was 10 months; for the survivors, 17.5 months.

Results

The underlying diseases in patients with A. non-fumigatus IA were acute lymphoblastic leukemia (37%) and acute myeloid leukemia (30%), aplastic anemia (10%), lymphoma (10%), myelodysplastic syndrome (6.5%), and chronic myelogenous leukemia (6.5%). Aspergillus non-fumigatus IA was more common found in allo-HSCT recipients (90%), than after chemotherapy (10%). At the moment of IA diagnosis, most patients received antifungal prophylaxis with fluconazole (83%) or echinocandins (6.7%). Breakthrough IA (prophylaxis with voriconazole, 2; posaconazole, 1) was documented in 10% of the patients. Causal agents were as follows: A. niger (60%), A. flavus (34%), A. glaucus (3%), and A. terreus (3%). The main sites of infection were lungs (80%), paranasal sinuses (10%), or combined affection of lung and paranasal sinuses (10%). For the diagnosed IA, 26 BAL, 6 sinus effusions and 1 pleural fluid sample were examined. In 57% cases, the mold hyphae were found by microscopy. 20% of IA cases with Aspergillus non-fumigatus developed in association with bacterial or other fungal infections (n=6): Klebsiella pneumonia, 33.3%; Pseudomonas aeruginosa, 33,3%; Kocuria kristinae, 16.7%; Trichoderma viridae, 16.7%. The median time for the onset of A. non-fumigatus IA after allo-HSCT was 155 (19-922) days. The following antifungal therapy was used in all the patients: voriconazole, in 73.3%; lipid amphotericin B, in 6.7%; posaconazole, in 6.7% of patients; combination therapy, in 13.3% of the cases. In 25% of the cases, A. non-fumigatus IA developed against the background of acute graft-versus-host diseases (GVHD) grade 2-3 + glucocorticoid therapy, and CMV reactivation (19% of this group). Overall survival at 12 weeks from the diagnosis of A. non-fumigatus IA was 83.3%. One lethal case could be attributed to the registered IA.

Aspergillus non-fumigatus invasive aspergillosis affected patients predominantly with acute leukemia (67%) and allo-HSCT recipients (90%). Aspergillus niger was the main etiology agent. In 20% cases IA developed in combination with other infections. Aspergillus non-fumigatus invasive aspergillosis was a late complication and developed against the background of CMV reactivation and acute GVHD. Overall survival at 12 weeks from the IA diagnosis was 83.3%.

Keywords

Hematological disorders, Aspergillus, diagnostics, treatment, survival.