Recombinant Bactericidal Permeability Increasing Protein (rBPI 21) For Endotoxin (Lipopolysaccharide, LPS) Neutralization During Hematopoietic Stem Cell Transplantation (HSCT): Phase I/II Clinical Trial Results

Abstract

Mucosal barrier injury caused by HSCT chemoradiotherapy conditioning leads to translocation of bacteria and bacterial products, including LPS-bearing bacteria and free LPS, into the systemic circulation. LPS signaling through its TLR4 receptor results in inflammatory cytokine release and resulting hypotension, fever, coagulopathy and end organ dysfunction. In allogeneic murine HSCT models, prior immunization to LPS, blockade of LPS:TLR4 signaling and use of LPS hyporesponsive mice all decrease HSCT morbidity and mortality, particularly acute GVHD and interstitial pneumonia.