title: Intestinal damage determines the inflammatory response and early complications in patients receiving conditioning for a stem cell transplantation.
abstract: BACKGROUND
  Stem cell transplantation (SCT) is still complicated by the occurrence of fever and inflammatory complications attributed to neutropenia and subsequent infectious complications. The role of mucosal barrier injury (MBI) of the intestinal tract therein has received little attention.
  
  
  METHODS
  We performed a retrospective analysis in 163 SCT recipients of which data had been collected prospectively on intestinal damage (citrulline), inflammation (C-reactive protein), and neutrophil count. Six different conditioning regimens were studied; 5 myeloablative (MA) and 1 non-myeloablative (NMA). Linear mixed model multivariate and AUC analyses were used to define the role of intestinal damage in post-SCT inflammation. We also studied the relationship between the degree of intestinal damage and the occurrence of early post-SCT complications.
  
  
  RESULTS
  In the 5 MA regimen there was a striking pattern of inflammatory response that coincided with the occurrence of severe intestinal damage. This contrasted with a modest inflammatory response seen in the NMA regimen in which intestinal damage was limited. With linear mixed model analysis the degree of intestinal damage was shown the most important determinant of the inflammatory response, and both neutropenia and bacteremia had only a minor impact. AUC analysis revealed a strong correlation between citrulline and CRP (Pearson correlation r = 0.96). Intestinal damage was associated with the occurrence of bacteremia and acute lung injury, and influenced the kinetics of acute graft-versus-host disease.
  
  
  CONCLUSIONS
  The degree of intestinal damage after myeloablative conditioning appeared to be the most important determined the inflammatory response following SCT, and was associated with inflammatory complications. Studies should explore ways to ameliorate cytotoxic therapy-induced intestinal damage in order to reduce complications associated with myeloablative conditioning therapy.
authors.affiliation: Department of Hematology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. w.vandervelden@hemat.umcn.nl
authors.forename: Walter J F M
authors.initials: WJ
authors.lastname: van der Velden
authors.forename: Alexandra H E
authors.initials: AH
authors.lastname: Herbers
authors.forename: Ton
authors.initials: T
authors.lastname: Feuth
authors.forename: Nicolaas P M
authors.initials: NP
authors.lastname: Schaap
authors.forename: J Peter
authors.initials: JP
authors.lastname: Donnelly
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: Blijlevens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016470:Bacteremia / Q000150:complications; D002097:C-Reactive Protein / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007249:Inflammation; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000002:abnormalities*; D008171:Lung Diseases / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009504:Neutrophils / Q000166:cytology; D011446:Prospective Studies; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D002097:C-Reactive Protein