Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group

Abstract

Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

Epidemiology, utilisation of healthcare resources and outcome of invasive fungal diseases following paediatric allogeneic haematopoietic stem cell transplantation

“…Candida and Aspergillus species were the predominant fungal organisms, and the lower respiratory tract and the bloodstream were the main sites of infection. These data are similar to those published from other centres . Most cases of IFDs were identified in the period beyond day + 180 post‐transplant.…”

“…CT, computed tomography; MRI, magnetic resonance imaging suspected IFDs is crucial for the overall management of these patients and justifies the considerable utilisation of resources for diagnosis and antifungal chemotherapy. Despite the existence of three classes of antifungal agents with potent activity against the majority of the relevant fungal pathogens, probable and proven IFDs continue to be a relevant cause for morbidity and have a significant impact on overall survival of paediatric allogeneic HSCT recipients.ACK N OWLED G M ENTSThe results of this analysis were presented in preliminary form at the 29th European Congress on Microbiology and Infectious Diseases,[13][14][15][16] April 2019, Amsterdam, The Netherlands (paper poster no. 2224, https ://www.escmid.org/escmid_publi catio ns/escmid_elibr ary/).CO N FLI C T O F I NTE R E S TAHG has received research grants from Gilead, Merck, Sharp & Dohme, and Pfizer; is or has been a consultant to Amplyx, Astellas, Basilea, F2G, Gilead, Merck, Sharp & Dohme, and Pfizer; and served at the speakers´ bureau of Astellas, Basilea, Gilead, Merck, Sharp & Dohme, Pfizer and Schering-Plough.…”

Fungal infections in children with haematologic malignancies and stem cell transplant recipients

“…The risk for IFD is increased in patients with GVHD due to both T‐cell dysfunction inherent to the disease and T‐cell suppressive therapies used to quell GVHD (Barnes & Marr, ). Acute GVHD, particularly high‐grade GVHD, has been reported as a potential risk factor for IFD in several single‐centre studies (Hovi et al ., ; Hale et al ., ; Srinivasan et al ., ), as well as one retrospective, multicentre study (Hazar et al ., ). Similarly, chronic GVHD has been identified as a risk factor for IFD (Hovi et al ., ; Kobayashi et al ., ; Hale et al ., ; Srinivasan et al ., ; Castagnola et al ., ).…”

Estimated burden of serious human fungal diseases in Turkey

“…However, these data are over 15 years old. In another retrospective study, the cumulative incidences of invasive fungal infections in Turkish paediatric allogeneic hematopoietic stem cell transplant (HSCT) recipients receiving fluconazole prophylaxis were 2.7%, 5.0% and 6.5% at 30, 100 and 180 days post‐transplantation, respectively. Among 408 patients, 77 (18.9%) died within 180 days after HSCT, and fungal infections accounted for 1.5% of these cases (6/408) (IFI‐related mortality).…”

“…Among 408 patients, 77 (18.9%) died within 180 days after HSCT, and fungal infections accounted for 1.5% of these cases (6/408) (IFI‐related mortality). The overall mortality (case fatality) rate for all types of IFI was 27% (7/26) at 180 days …”