title: Mucositis not neutropenia determines bacteremia among hematopoietic stem cell transplant recipients.
abstract: BACKGROUND
  In the 1960s, it was reported that infectious complications were the main cause of fever during neutropenia that followed hematopoietic stem cell transplant (HSCT). More recently, mucositis has become recognized as an important determinant of the inflammatory response and infectious complications.
  
  
  METHODS
  The objective of this prospective study was to determine the impact of intestinal mucositis, as measured by plasma citrulline, and neutropenia on the systemic inflammatory response (C-reactive protein) and the occurrence of bacteremia among 2 cohorts of HSCT recipients: 1 composed of 18 patients who had been treated with a myeloablative (MA) regimen (high-dose melphalan) and the other involving 19 patients who had received the non-myeloablative (NMA) regimen (fludarabine and cyclophosphamide). Blood cultures were obtained for surveillance from admission onwards as well as at the onset of fever.
  
  
  RESULTS
  The MA regimen induced severe intestinal mucositis manifest by citrullinemia <10 μmol/L, which was accompanied by an inflammatory response, and bacteremia affected 8 (44%) of 18 patients and coincided with the nadir of citrullinemia. By contrast, those who had been treated with the NMA regimen did not develop severe intestinal mucositis, had a moderate inflammatory response, and only 2 (11%) of the 19 patients developed bacteremia. However, both groups experienced profound neutropenia and its duration was significantly longer for those receiving the NMA regimen.
  
  
  CONCLUSIONS
  This study suggests that severe intestinal mucositis, i.e., citrullinemia <10 μmol/L, defines the period of risk of bacteremia better than does neutropenia, and that measuring plasma citrulline may prove useful in deciding who needs empirical antimicrobial therapy and when.
authors.affiliation: Department of Hematology, Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: A H E
authors.initials: AH
authors.lastname: Herbers
authors.forename: A F J
authors.initials: AF
authors.lastname: de Haan
authors.forename: W J F M
authors.initials: WJ
authors.lastname: van der Velden
authors.forename: J P
authors.initials: JP
authors.lastname: Donnelly
authors.forename: N M A
authors.initials: NM
authors.lastname: Blijlevens
mesh_terms: D000328:Adult; D000368:Aged; D016470:Bacteremia / Q000209:etiology*; D002097:C-Reactive Protein / Q000378:metabolism; D002956:Citrulline / Q000097:blood; D003520:Cyclophosphamide / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000009:adverse effects; D008875:Middle Aged; D052016:Mucositis / Q000097:blood / Q000139:chemically induced*; D019653:Myeloablative Agonists / Q000009:adverse effects*; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced*; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D019653:Myeloablative Agonists; D002956:Citrulline; D003520:Cyclophosphamide; D002097:C-Reactive Protein; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan
keywords: citrulline; hematopoietic stem cell transplant; high-dose melphalan; infections; mucositis; reduced intensity