The serum IL-12:IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation.
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-1beta, IL-2, IL-6, IL-8, IL-10, IL-12(p70), TNF-alpha and IFN-gamma 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.


RESULTS
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.


CONCLUSIONS
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.
Tuma
Ra
R
Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10121, USA.
Almyroudis
Ng
N
Sohn
Sj
S
Panageas
K
K
Rice
Rd
R
Galinkin
D
D
Blain
M
M
Montefusco
M
M
Pamer
Eg
E
Nimer
Sd
S
Kewalramani
T
T
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D005260:Female; D005334:Fever / Q000097:blood / Q000276:immunology / Q000382:microbiology; D006801:Humans; D018664:Interleukin-12 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D033581:Stem Cell Transplantation / Q000009:adverse effects; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
D015850:Interleukin-6; D018664:Interleukin-12