Infection Burden and Timing in the First Year After Pediatric Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience

Abstract

Abstract Background Infection is a leading cause of morbidity and non-relapsed mortality (NRM) after allogeneic hematopoietic cell transplant (allo-HCT). This study aimed to describe the contemporary epidemiology of infections, overall survival (OS) as well as NRM at 1 year post pediatric allo-HCT. Methods Retrospective review of laboratory-confirmed infections among patients who underwent first allo-HCT from January 2014 to December 2020 at a single, quaternary pediatric hospital. Cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV) and Human Herpes Virus-6 (HHV-6) weekly viral surveillance was performed on blood using polymerase chain reaction until day +100. We reviewed Clostridioides difficile, bacterial blood stream infections (BSIs), and fungemia until 1 year post allo-HCT or death. Results During the six-year study period, 146 subjects underwent allo-HCT at a median age of 8.75 years (IQR 2.6-14.28), predominantly males (58%) with hematologic malignancies (60%), and bone marrow as stem cell source (71%). Matched unrelated donors were used in 53% after myeloablative conditioning in 62%. A total of 126 patients (86%) experienced at least one infection, primarily with DNA viral infections (n=113, 77%). EBV DNAemia occurred in 50%, CMV in 30%, HHV-6 in 23%, and AdV in 17%. The time to first DNAemia detection post HCT was 15 days for CMV (IQR 6-28.5), 20 days for AdV (IQR 6-89), 22 days for HHV-6 (IQR 17-31), and 55 days for EBV (IQR 41-92.5). Bacterial BSIs were identified in 37% (54/146) of patients at a median of 12.5 days post-HCT (IQR 5-146.3), 80% (43/54) experienced a single episode, while 20% (11/54) had multiple episodes, resulting in 68 BSIs total. Among all BSIs, 38% (26/68) were classified as mucosal barrier injury laboratory confirmed bloodstream infections, while 59% (40/68) as central line associated BSIs. In total, 89 pathogens were identified. Gram-negative pathogens (GN) were predominant in 56% (50/89) of the isolates, with lactose fermenters representing 72% (36/50). Gram-positive pathogens (GP) accounted for 44% (39/89), primarily Staphylococcus species (36%, 14/39, predominantly Staphylococcus aureus in 10 cases) and Viridans Group Streptococcus (31%, 12/39). Clostridioides difficile was detected by PCR in 19% (27/146), with a median onset of 54 days post-HCT (IQR 19-125). Fungemia occurred on 3% (4/146) at a median of 150 days post-HCT (IQR 40.23 - 226.8), 3 had candidemia and 1 had fusariosis. The overall mortality rate at 1 year was 15% (22/146), with a median time from transplant to death of 188 days (IQR 44-233.5) and documented active infection at the time of death in 41% (9/22). Only the presence of fungemia showed a significantly difference in OS (25% vs 87%, p < 0.0001) and NRM (50% vs 5.6%, p < 0.001) Conclusions Infections occurred frequently in our cohort affecting 86% (126/146), most commonly as viral DNAemia [77% (113/146)] with EBV > CMV > HHV-6 > AdV, followed by bacterial BSI [37% (54/146)] with GN (56%) vs GP (44%). Despite CLABSI prevention efforts, CLABSI occurred 40 (59%) of total bacterial BSI episodes. Despite the higher frequency of bacterial and viral infections, only fungemia was significantly associated with decreased OS and higher NRM.