Plasma cytokine and soluble receptor signature predicts outcome of patients with classical Hodgkin's lymphoma: a study from the Groupe d'Etude des Lymphomes de l'Adulte.
OBJECTIVE
Approximately 15% of patients with localized and 30% with disseminated classical Hodgkin's lymphoma fail to respond or relapse after first-line treatment. Usual prognosis scoring systems are actually unable to identify this small subset of patients with good confidence, pointing out the need for additional prognostic biomarkers.


METHODS
We prospectively analyzed the prognosis value of plasma levels of tumor necrosis factor (TNF), its soluble receptors TNF-R1 and TNF-R2, IL-10, IL1-RA, IL-6, and soluble CD30 (sCD30) when taken before any treatment in 519 consecutive patients with a first diagnosis of classical Hodgkin's lymphoma.


RESULTS
Levels of TNF higher than 46 pg/mL, TNF-R1 higher than 3 ng/mL, TNF-R2 higher than 5 ng/mL, IL-10 higher than 30 pg/mL, IL1-RA higher than 668 pg/mL, IL-6 higher than 30 pg/mL, and sCD30 higher than 80 U/mL were associated with poor event-free and overall survival. In multivariate analysis, high levels of IL1-RA, IL-6, and sCD30 were independent poor prognosis factors, and the cytokine signature based on their combination allowed the stratification of patients in four prognosis classes, reaching a 5-year event-free survival probability of 92%, 85%, 76%, and 15%, respectively. This index was more potent than other scoring systems to predict patient event-free survival, and remained independent from the international prognostic score (P < .001), adding significant prognostic information to its predictive power.


CONCLUSIONS
Plasma cytokine signature is sufficient to predict disease-related outcome in classical Hodgkin's lymphoma, and allows the identification of patients with very high risk of treatment failure.
Casasnovas
René-Olivier
RO
Service d'hématologie clinique, Hôpital Le Bocage, Centre Hospitalier Universitaire Dijon, Dijon, France. olivier.casasnovas@chu-dijon.fr
Mounier
Nicolas
N
Brice
Pauline
P
Divine
Marine
M
Morschhauser
Franck
F
Gabarre
Jean
J
Blay
Jean-Yves
JY
Voillat
Laurent
L
Lederlin
Pierre
P
Stamatoullas
Aspasia
A
Bienvenu
Jacques
J
Guiguet
Michel
M
Intrator
Liliane
L
Grandjean
Monique
M
Brière
Josette
J
Ferme
Christophe
C
Salles
Gilles
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000097:blood*; D006689:Hodgkin Disease / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D018121:Receptors, Cytokine / Q000097:blood*; D016019:Survival Analysis; D016896:Treatment Outcome
D016207:Cytokines; D018121:Receptors, Cytokine