Acute gastrointestinal graft-vs-host disease is associated with increased enteric bacterial bloodstream infection density in pediatric allogeneic hematopoietic cell transplant recipients

Abstract

Background: Bacterial septicemia remains the leading cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (AlloHCT). While murine studies have found acute gastrointestinal graft-vs-host disease (aG-GVHD) to be associated with increased incidence of enteric bacterial bloodstream infections (EB-BSI), this association has not been studied in humans. We hypothesized that in patients who developed aG-GVHD, the EB-BSI density after onset of aG-GVHD would be higher than before onset and higher than in patients without acute GVHD (aGVHD).

Methods: We retrospectively reviewed data collected on 264 pediatric AlloHCT recipients with malignant and nonmalignant disease. We calculated and compared EB-BSI densities in the following 3 subgroups: patients without aGVHD and patients with aG-GVHD, both before and after onset of aG-GVHD. We also examined the effect of aG-GVHD onset on the first episode of EB-BSI using Cox proportional hazards models.

Results: The overall incidence of aG-GVHD was 28.8% (n = 76). Analyses done both at 120 and 180 days post-AlloHCT showed that the EB-BSI density increased after aG-GVHD onset (0.95 infections/person-year before aG-GVHD vs 2.7 infections/person-year after aG-GVHD at day 120 [P = .006]; 0.95 infections/person-year before aG-GVHD vs 2.26 infections/person-year after aG-GVHD at day 180 [P = .033]). On multivariate analysis, the onset of aG-GVHD had a positive hazard ratio of 1.47 (P = .077) on time to first EB-BSI.

Conclusions: Our results support the theory that aG-GVHD predisposes pediatric AlloHCT recipients to EB-BSI. Prophylactic agents such as probiotics should be studied prospectively in patients with aG-GVHD.

Keywords: AlloHCT; BSI; GVHD.