Outcomes of invasive fungal infections in 358 children undergoing allogeneic haematopoietic stem cell transplantation: A prospective UK study
Giorgio Ottaviano, Emanuele Lanino, Zohreh Nademi, Beki James, Madeleine Powys, Persis Amrolia, Kanchan Rao, Juliana Silva, Arina Lazareva, Sarah Lawson, Katharine Patrick, Caroline Furness, Olga Tatarinova, Bilyana Doncheva, Adam Irwin, Anoop Cherungonath, Joseph Frank Standing, Adilia Warris, Robert ChiesaSummary
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.