PI-03. Invasive aspergillosis in patients with hematological malignancies due to cryptic pathogens
Vladislav V. Markelov1, Marina O. Popova1, Yuliya A. Rogacheva1, Olga N. Pinegina1, Alisa G. Volkova1, Ilia Y. Nikolaev1, Nikita P. Volkov1, Tatiana S. Bogomolova2, Oleg V. Goloshchapov1, Olesya V. Paina1, Yulia Yu. Vlasova1, Sergey N. Bondarenko1, Nikolay N. Klimko1,2, Ludmila S. Zubarovskaya1, Alexander D. Kulagin1
1 RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
2 I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, St. Petersburg, Russia
Contact: Vladislav V. Markelov, e-mail: marckelov.vladislav5@mail.ru
Summary
Rare invasive mycoses are becoming an increasingly important medical issue in immunosuppressed patients. Emergence and improvement of new diagnostic methods led to identification of new pathogens. Among the Aspergillus genus, some species not related to Aspergillus (Asp.) fumigatus, Asp. niger, Asp. flavus and Asp. terreus were named “cryptic”. This group of cryptic fungi may represent clinical challenges due to their resistance to antifungals. The aim of our study was to describe patients with hematological malignancies with invasive aspergillosis (IA) caused by cryptic Aspergillae.
Patients and methods
From 2016 to 2021 years, 10 cases of probable cryptic IA were registered in CIC 725, according to EORTC/MSG 2020 criteria.
Results
Patients baseline characteristics included age, gender, primary disease, its clinical status, treatment modes (especially, HSCT). Dominant underlying disease was Non-Hodgkin lymphoma (n=4; 40%). The median age at the IA diagnosis was 34 years (10-66). Nine patients (90%) underwent hematopoietic stem cell transplantation (HSCT): 8 patients received allogeneic grafts (allo-HSCT), one patient had autologous HSCT. Allo-HSCT from HLA-matched related donor (MRD), match-unrelated donor (MUD), and haploidentical (Haplo) were performed in 3 (30%), 2 (20%) and 3 (30%) patients, respectively. The main causal pathogen was Asp. nidulans (n=4, 40%). Combination of Aspergillus species was observed in 2 patients (20%). Fungal co-infection was diagnosed in 3 patients (30%), i.e., 2 cases with Penicillium spp., and Lichtheimia ramose was revealed in one patient. Bacterial and viral co-infections were registered in 6 patients (60%). In all cases, the infection affected lungs (n=10, 100%). Clinical manifestations included fever in 5 patients (50%), cough (in 5 cases, 50%), and dyspnea reported in 3 cases (30%). The median term of IA development after HSCT was 309 days (35 to 2303). Primary antifungal prophylaxis included fluconazole (Flu) administered in 5 cases (56%), voriconazole (Vor) applied in 2 patients (22%), posaconazole (Pos), in 1 case (11%), and echinocandin (Echin), in 1 patient (11%). One patient received secondary prophylaxis with Vor. At the time of IA development, 3 patients (30%) received glucocorticosteroids for the treatment of severe GVHD. Frontline therapy included Vor (n=8, 80%), liposomal amphotericin B (Amph B) as monotherapy (n=1, 10%), or in combination with Pos (n=1, 10%). Second- and third-line therapies were required in 1 patient (10%), with IA due to Asp.calidoustus: Amph B + Echin and Amph B + isavuconazole. A single lethal case could be attributed to IA, this patient died on day 45 after IA diagnosis. Overall survival at 12 weeks was 90%.
Conclusion
Asp. nidulans is the most common agent causing IA by cryptic Aspergillus spp. No specific clinical symptoms and sites of lesions could be specified in these cases. Cryptic IA may often develop in combination with other fungal agents, together with bacterial and viral infections. In HSCT recipients, сryptic IA is a longitudinal post-transplant complication with, generally, good prognosis.
Keywords
Stem cell transplantation, Aspergillus, invasive aspergillosis, infectious complications.
