Multiplex analysis of blood cytokines as a prognostic tool in HIV related non-Hodgkin lymphoma patients: a potential role of interleukin-7.
BACKGROUND
Recent studies suggest a powerful prognostic value for blood cytokine levels in different diseases. Non-Hodgkin lymphoma (NHL) still represents one of the main causes of death in the HIV setting, with a wide variation in outcome and survival among patients. We measured blood concentrations of 11 cytokines from HIV-NHL patients at diagnosis and correlated these with the patient outcome to evaluate the prognostic value.


METHODS
Luminex technology was used to simultaneously measure serum levels of interleukin IL-2/5/6/7/8/10/13/15, INF-γ, TNF-α and VEGF. Eighty-one consecutive HIV-NHL patients, at diagnosis, were studied. Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) of disease-free survival (DFS) and overall survival (OS) were computed according to cytokine levels. HRs were also calculated for continuous variation of IL-7.


RESULTS
In the multivariate analysis, statistically significant associations to both DFS and OS were found for IL-7 serum levels ≥ 3.2 pg/mL (HR=5.55, 95%CI:2.38-12.95; HR=3.53, 95%CI:1.60-7.77, respectively), IL-8 ≥ 18 pg/mL (HR=2.69, 95%CI:1.15-6.30; HR=2.35, 95%CI:1.01-5.51, respectively) and IL-10 ≥ 13 pg/mL (HR=2.82, 95%CI: 1.19-6.71; HR=2.98, 95%CI:1.21-7.30, respectively). When the multivariate analyses were mutually adjusted for INF-γ, IL-7, IL-8, IL-10 and IL-15, serum IL-7 ≥ 3.2 pg/mL emerged as factor independently associated to increased risk of DFS (HR=3.63, 95%CI:1.47-8.93) and OS (HR=3.97, 95%CI:1.49-10.57).


CONCLUSIONS
IL-7, measured at NHL diagnosis, was the only cytokine strongly and independently associated to both DFS and OS. The multiplex analysis of different blood cytokines' concentration might be useful in defining additive predictive markers in HIV-NHL management and ascertainment of their outcome.
Microbiology-Immunology and Virology Unit, Centro di Riferimento Oncologico, IRCCS, via F. Gallini 2, 33081 Aviano, Italy. mtbortolin@cro.it
Maria Teresa
MT
Bortolin
Rosamaria
R
Tedeschi
Ettore
E
Bidoli
Stefania
S
Zanussi
Chiara
C
Pratesi
Emanuela
E
Vaccher
Umberto
U
Tirelli
Paolo
P
De Paoli
D000328:Adult; D016207:Cytokines / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications; D006801:Humans; D007118:Immunoassay / Q000706:statistics & numerical data; D015851:Interleukin-7 / Q000097:blood*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models
D016207:Cytokines; D015851:Interleukin-7