Invasive Aspergillosis in Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Large Cohort Single-Center Study
Authors: Rogacheva Yuliya A. , Markelov Vladislav V. , Popova Marina O. , Volkova Alisa G. , Nikolaev Ilya Y. , Pinegina Olga N. , Ignatyeva Svetlana M. , Bogomolova Tatiyana S. , Bondarenko Sergey N. , Klimko Nikolay N. , Kulagin Alexander D. 
Published: November 2021

Abstract
Background . Invasive aspergillosis (IA) is dominant among invasive fungal infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The emergence of new immunosuppressive drugs, the expanding use of antifungal agents with activity against Aspergillus spp. on the one hand, and the improvement of the diagnostics and therapy on the other hand affect epidemiology of IA.
Methods. We analyzed 663 patients who underwent allo-HSCT from 2016 to 2020 years in CIC 725. During the observation period, 43 patients with proven and probable IA were included into analysis. According to EORTC/MSG 2019 criteria, 2 proven and 41 probable cases were diagnosed in adults with hematological malignances and non-malignant hematological diseases during 1 year after allo-HSCT. We characterized the IA after allo-HSCT and conducted the comparative analysis of patients and transplant characteristics who developed IA after allo-HSCT and did not. The median follow up time was 13,9 months.
Results. Cumulative incidence of IA during 1-year period after allo-HSCT was 8%. Among all cases of IA most common underlying diagnoses were acute leukemia - 32% and lymphomas - 30%. The main sites of infection were lungs 93%, sinuses - 2%, disseminated lesions - 5%. The IA was diagnosed by bronchoalveolar (BAL) or sinuses liquid culture in 54% cases, and the etiology were Aspergillus fumigatus - 8 (42%), Aspergillus niger - 5 (26%), Aspergillus flavus - 2 (11%), Aspergillus terreus - 1 (5%), Aspergillus spp. - 3 (16%). The median day of IA onset was day +59 (range, 2 to 282) after allo-HSCT. First line therapy of IA was predominantly with voriconazole (vori) monotherapy - 35 (81%), combination based on vori - 5 (12%). Salvage combination therapy were prescribed in two patients: vori + echinocandins (echino) and L amph B + echino. Overall survival at 12 weeks in patients with IA was 76%. Comparative analysis showed that in patients with IA statistically significant more frequent were patients with AML, HL, NHL, Ph(-) MPNs, second or more allo-HSCT, CMV-reactivation, aGVHD, aGVHD grade 3-4, severe chGVHD (Table 1). To identify the risk factors including primary antifungal prophylaxis planning to conduct the multivariate subgroup analysis. Patients with IA had lower level of lymphocytes on day +60 (p=0.006) and 100 (p=0.009) compared to patients without IA (pic.1).
Conclusions. Incidence of IA after allo-HSCT was 8% with the median day +59. The main site of infection was lungs, etiology - Aspergillus fumigatus. Overall survival at 12 weeks in patients with IA was 76%. In the era of primary and secondary prophylaxis we identified risk groups for developing IA after allo-HSCT among the previously undescribed, worthy of further study: subsequent allo-HSCT, underlying disease: HL, NHL, Ph (-) MPNs.
Figure 1 Figure 1.

Disclosures
Klimko: Gilead Sciences, MSD, Pfizer Pharmaceuticals, and Astellas Pharma: Speakers Bureau; Gilead Science, MSD, Pfizer: Membership on an entity's Board of Directors or advisory committees. Kulagin: Pfizer: Speakers Bureau; Johnson & Johnson: Speakers Bureau; Roche: Speakers Bureau; Sanofi: Speakers Bureau; Generium: Speakers Bureau; Biocad: Research Funding; Apellis: Research Funding; Alexion: Research Funding; X4 Pharmaceuticals: Research Funding; Novartis: Speakers Bureau.