Endotoxemia and elevation of lipopolysaccharide-binding protein after hematopoietic stem cell transplantation

Background. Hematopoietic stem cell transplantation (SCT) carries a significant risk of severe therapy-associated complications chief among which is acute graft vs. host disease (aGVHD). Animal models indicate that myeloablative chemotherapy compromises the mucosal barrier, thereby allowing translocation of intestinal flora-derived lipopolysaccharides (or endotoxin) that subsequently trigger aGVHD, but there are no comparable data in humans. Our aim was to gain insight into the potential role of endotoxin and endotoxin-induced acute phase proteins in children undergoing SCT. Methods. Plasma concentrations of C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) were measured in 57 pediatric patients undergoing SCT. In addition plasma endotoxin levels were measured in 25 patients. Results. The previously described rise in CRP was confirmed, and a marked elevation of LBP was observed that peaked at Day 7 (median value, 6.6 mug/ml; P < 0.03 for all pairwise comparisons). CRP and LBP values were significantly correlated (r = 0.77, P < 0.001). A significant but complex relationship was noted between LBP concentrations at Day 0 and severity of subsequent aGVHD (P = 0.02). Of the 25 patients assayed, 11 (44%) had detectable endotoxemia, including 4 who were endotoxin-positive at Day 0. Conclusions. The detection of endotoxemia coupled with marked elevations in LBP at Day 7 raises the possibility that inflammatory responses early after SCT may be driven in part by the entry of lipopolysaccharide into the bloodstream.