title: Risk factor for death in hematopoietic stem cell transplantation: are biomarkers useful to foresee the prognosis in this population of patients?
abstract: BACKGROUND
  The morbidity and mortality in hematopoietic stem cell transplantation (HSCT) occur due to infectious complications and constitute the major clinical problems in HSCT recipients. The role of the use of biomarkers in post-HSCT patients is still controversial.
  
  
  OBJECTIVE
  To assess the serum values of biomarkers interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) and risk factors for post-HSCT death.
  
  
  METHODS
  Prospective study conducted in patients submitted to HSCT at a university hospital. Biomarkers (IL-6, PCT and CRP) were assessed on the day afebrile neutropenia was detected, in the febrile event, 24 and 72 h after fever onset and 48 h or 5 days if fever persisted. Patients were compared as to the death outcome within 30 days from the HSCT. Variables with p < 0.15 were included in the multivariate analysis model (MVA) that were performed for all patients included in the study and separated for autologous and allogeneic HSCT patients.
  
  
  RESULTS
  296 patients with ages ranging between 15 and 70 years, neutropenic, submitted to HSCT, being 216 (73%) autologous and 80 (20%) allogeneic were assessed. One hundred and ninety (64.2%) patients presented fever after the transplantation and infection microbiologically controlled in 78 (26.4%). Twenty-three cases (7.8%) evolved to death. The risk factors associated with death in the bivariate analysis were age, allogeneic transplantation, unrelated transplantation, GVHD, bloodstream infection by Gram-negative, IL-6 >140 pg/mL and CRP ≥ 120 mg/L and the protective ones were lymphoma and hospital outpatient support. The independent variables in the MVA associated with death were allogeneic and unrelated transplantation, blood stream infection (BSI) by Gram-negative, LDH ≥ 390 UI/L, urea ≥ 25 mg/dL and CRP ≥ 120 mg/L for HSCT transplanted patients and BSI due to Gram-negative and CRP ≥ 120 mg/L for allogeneic HSCT, however, CRP ≥ 120 mg/L did not remain in the model when urea ≥ 25 mg/L was included. No independent risk factor was found for autologous patients.
  
  
  CONCLUSIONS
  Out of the biomarkers assessed, only CRP ≥ 120 mg/L was independently associated with death. Other risk factors found were: type of transplantation (allogeneic and unrelated), bloodstream infection by Gram-negative, LDH ≥ 390 UI/L and urea ≥ 25 mg/dL. For allogeneic patients only CRP ≥ 120 mg/L and BSI due to Gram-negative were risk factors for death; however, CRP did not remain in the model when urea ≥ 25 mg/L was included.
authors.affiliation: Infectious and Parasitary Diseases Department, School of Medicine, Universidade de São Paulo, Lim54, São Paulo, Brazil.
authors.forename: K S R
authors.initials: KS
authors.lastname: Massaro
authors.forename: R
authors.initials: R
authors.lastname: Macedo
authors.forename: B S
authors.initials: BS
authors.lastname: de Castro
authors.forename: F
authors.initials: F
authors.lastname: Dulley
authors.forename: M S
authors.initials: MS
authors.lastname: Oliveira
authors.forename: M A S
authors.initials: MA
authors.lastname: Yasuda
authors.forename: A S
authors.initials: AS
authors.lastname: Levin
authors.forename: S F
authors.initials: SF
authors.lastname: Costa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D064147:Febrile Neutropenia / Q000097:blood* / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D015850:Interleukin-6; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide