The serum IL-12:IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation Journal Article


Authors: Tuma, R. A.; Almyroudis, N. G. ; Sohn, S. J.; Panageas, K.; Rice, R. D.; Galinkin, D.; Blain, M.; Montefusco, M.; Pamer, E. G.; Nimer, S. D.; Kewalramani, T.
Article Title: The serum IL-12:IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation
Abstract: Background: Fever during neutropenia and after neutrophil engraftment (post-engraftment fever) occurs commonly during autologous transplantation (ASCT), but infections are infrequently identified. Tests that reliably exclude infection may reduce the cost and toxicity of unnecessary diagnostic testing and empiric treatment. We assessed whether serum levels of inflammatory cytokines could distinguish infectious from non-infectious causes of fever in patients undergoing ASCT. Methods: Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL- 12(p70), TNF-α and IFN-γ were measured by sandwich ELISA at multiple pre-determined times and at the onset of the first fever during neutropenia and after neutrophil engraftment in patients with hematologic malignancies undergoing ASCT. Standard clinical criteria were used to assess for the presence of infection. Result: Seventy-two febrile episodes occurred in 54 of 65 enrolled patients; 29 (40%) of the episodes occurred after neutrophil engraftment. Infections were identified as the cause of 28% and 24% of the neutropenic and post-engraftment febrile episodes, respectively. The level of IL-12 decreased and that of IL-6 increased significantly during fever because of infection, such that the IL-12:IL-6 ratio accurately excluded infection. The area under the ROC curve for the IL-12:IL-6 ratio was 0.88 (95% CI 0.79-0.97). The sensitivity, specificity, positive predictive and negative predictive values associated with a cut-off ratio of 4.1 were 95%, 75%, 60%, and 97%, respectively. Discussion: The IL-12:IL-6 ratio effectively discriminates infectious from non-infectious causes of fever during ASCT. It may be useful in assessing the probability of infection in patients with post-engraftment fever.
Keywords: adult; controlled study; aged; middle aged; antibiotic agent; major clinical study; diagnostic accuracy; sensitivity and specificity; protein blood level; interleukin 2; multiple myeloma; interleukin 10; interleukin 12p70; interleukin 1beta; interleukin 8; aciclovir; antifungal agent; amyloidosis; autologous stem cell transplantation; stem cell transplantation; enzyme linked immunosorbent assay; prediction; hodgkin disease; febrile neutropenia; fever; pneumonia; confidence interval; cytokine; hematologic malignancy; nonhodgkin lymphoma; longitudinal studies; tumor necrosis factor alpha; gamma interferon; diagnostic value; probability; ciprofloxacin; transplantation conditioning; interleukin 6; interleukin-6; area under curve; reliability; bacteremia; infection prevention; cotrimoxazole; transplantation, autologous; fluconazole; interleukin 12; roc curve; autologous transplantation; il-6; interleukin-12; il-12
Journal Title: Cytotherapy
Volume: 8
Issue: 4
ISSN: 1465-3249
Publisher: Elsevier Science Ltd.  
Date Published: 2006-08-01
Start Page: 327
End Page: 334
Language: English
DOI: 10.1080/14653240600845237
PUBMED: 16923608
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 4 June 2012" - "CODEN: CYTRF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Roman Tuma
    5 Tuma
  2. Sejean Sohn
    7 Sohn
  3. Eric Pamer
    249 Pamer
  4. Stephen D Nimer
    345 Nimer
  5. Katherine S Panageas
    329 Panageas
  6. Robert D Rice
    27 Rice
  7. Melissa M Blain
    2 Blain