Invasive Fungal Disease in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in China: A Multicenter Epidemiological Study (CAESAR 2.0)

Abstract

Background This study (China Assessment of Antifungal Therapy in Hematological Diseases, CAESAR 2.0) aimed to provide updated epidemiological data on invasive fungal disease (IFD) in patients undergoing allogeneic stem cell transplantation (allo-HSCT). Methods This multicenter, real-world, observational study was conducted at 12 allo-HSCT centers in China between January 2021 and December 2021. Consecutive adult patients (≥18 years) who underwent allo-HSCT with antifungal prophylaxis were included. IFD was diagnosed according to the 2019 criteria of the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG). Follow-up was completed by December 31, 2022. Results A total of 2015 patients were collected. mold-active antifungal prophylaxis was used in 76.08% of patients, which included mainly voriconazole (44.37%) and posaconazole (31.71%). The cumulative incidence of IFD (proven and probable) at 1 year after allo-HSCT was 6.3%. Pathogens were identified in 47.97% of IFD cases and mainly included Candida spp. (17.89%), Mucorales (13.01%), Aspergillus spp. (8.94%), and Pneumocystis jirovecii (6.5%). Multivariate analysis identified the following factors associated with IFD: disease at advanced stage (hazard ratio [HR]= 2.55; 95% confidence interval [CI]: 1.58-4.12 P<0.001), absolute neutrophil count (ANC) engraftment (≤28 days) (HR=0.37; 95% CI: 0.15-0.92 P=0.032), platelet (PLT) engraftment (≤28 days) (HR=0.41; 95% CI: 0.27-0.62 P<0.001) and acute graft-versus-host disease grade III-IV (HR=2.97; 95% CI: 1.97-4.49 P<0.001). The IFD-attributable mortality rate was 48.28%. Conclusions Despite the widespread use of mold-active prophylaxis, the risk of IFD after allo-HSCT remains high. The most common pathogens are Candida spp., Mucorales, Aspergillus spp., and Pneumocystis jirovecii.