Outcomes of invasive fungal infections in 358 children undergoing allogeneic haematopoietic stem cell transplantation: A prospective UK study.

The optimal strategy to prevent and treat invasive fungal infections (IFIs) in children receiving allogeneic haematopoietic stem cell transplantation (HSCT) is not well established. A paediatric bone marrow transplant (BMT) working group set up UK national guidelines for the management of IFI and conducted a prospective study to assess the impact of these on incidence and outcomes. From March 2017 to December 2021, 358 children who received HSCT were prospectively included. Most children (82%) received either itraconazole (41%) or liposomal amphotericin B (41%) prophylaxis with a median duration of 170 days (interquartile range [IQR] 101-279). Cumulative incidence of possible/probable/proven IFI at 1 year was 17.6%, with no significant differences in children receiving itraconazole or liposomal amphotericin B (15.7% vs. 15.9%, 0.997). In multivariate analysis models (Fine-Gray hazard ratio) underlying malignant disease and low azoles therapeutic drug monitoring levels were independently associated with development of IFI. Children with probable/proven IFI had a higher 1-year transplant-related mortality (22% vs. 5.7%, Gray's test, p < 0.001). By adopting standardized anti-fungal prophylaxis, the incidence of proven/probable IFI in a large cohort of transplanted children was 5% and these showed significant decreased survival, warranting tailored prophylactic strategies in high-risk patients.