title: Procalcitonin and cytokine profiles in engraftment syndrome in pediatric stem cell transplantation.
abstract: Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT.
  
  
  
  We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100. Patients were evaluated for ES, infection and acute graft-versus-host disease. Cytokines were analyzed by values at engraftment, and also compared to pre-conditioning and day 0 values to evaluate for change from baseline.
  
  
  
  A total of 30 subjects (median age: 7 years, min.-max.: 1-21 years) were enrolled of whom 5 had ES. Characterization of the cytokine profile revealed differences between day 0 from pre-HSCT, with a trend towards differences in IL-10, IL-12p70, interferon-γ and TNF-α at the time of ES. For IL8 and procalcitonin, there was evidence that the absolute difference (or fold change) between engraftment and pre-conditioning or day 0 differed according to ES. In particular, procalcitonin increased from baseline (15.1 median fold increase in ES+ versus 2.31 median fold increase in ES-, P = 0.0006, median difference: 13.8, 95% confidence interval: 6.33, 65.6).
  
  
  
  Our data provide one of the first prospective studies evaluating cytokines in pediatric allogeneic HSCT and suggest that elevated procalcitonin may serve as a biomarker for ES. Further studies to evaluate this finding are warranted.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland.
authors.forename: Nirali N
authors.initials: NN
authors.lastname: Shah
authors.affiliation: Division of Blood and Marrow Transplantation, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Watson
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Yates
authors.affiliation: Biostatistics and Data Management Section, Office of the Clinical Director, CCR, NCI, NIH, Bethesda, Maryland.
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.affiliation: Biostatistics and Data Management Section, Office of the Clinical Director, CCR, NCI, NIH, Bethesda, Maryland.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Division of Blood and Marrow Transplantation, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC.
authors.forename: David
authors.initials: D
authors.lastname: Jacobsohn
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland.
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Fry
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D019337:Hematologic Neoplasms / Q000150:complications* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D002116:Calcitonin
keywords: engraftment syndrome; pediatric; procalcitonin; stem cell transplantation