title: Prognostic significance of pretreatment serum cytokines in classical Hodgkin lymphoma.
abstract: OBJECTIVE
  Although the International Prognostic Score (IPS) is the gold standard for risk-stratifying patients with classical Hodgkin lymphoma (cHL), these criteria do not accurately predict outcome. As cytokines are critically involved in driving cHL, we tested whether pretreatment serum cytokine levels could provide additional prognostic information.
  
  
  METHODS
  Thirty cytokines were measured in pretreatment serum from 140 patients with cHL and compared with 50 nonlymphoma controls. Patients were followed for event-free survival (EFS) and overall survival (OS), and Cox proportional hazards regression models were used to assess the association of individual cytokines and the cytokine profiles with outcome via unadjusted and IPS-adjusted HR.
  
  
  RESULTS
  Twelve cytokines (EGF, bFGF, G-CSF, HGF, IL-6, IL-8, IL-12, IL-2R, IP-10, MIG, TNF-α, and VEGF) were significantly (P < 0.05) higher in patients with cHL than controls; elevated levels of HGF, IL-6, IL-2R, IP-10, and MIG were all associated with poorer EFS. Only interleukin-2 receptor (IL-2R; P = 0.002) and interleukin (IL)-6 (P < 0.001) were independently prognostic. Patients with increased IL-6 and IL-2R had a significantly higher risk of early relapse and death, a finding that remained significant even after IPS-based risk stratification. Although elevated IL-6 and IL-2R correlated with the IPS, soluble CD30 (sCD30), and thymus and activation-related chemokine (TARC) levels, the two-cytokine model remained independently predictive of prognosis.
  
  
  CONCLUSIONS
  Elevated pretreatment serum cytokines are associated with increased disease relapse and inferior survival in cHL. Thus, the pretreatment cytokine profile, particularly serum levels of IL-6 and IL-2R, may be used to identify patients with cHL at high risk for early-disease relapse.
authors.affiliation: Authors' Affiliations: Divisions of Hematology and Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota; and Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Preethi Reddy
authors.initials: PR
authors.lastname: Marri
authors.forename: Lucy S
authors.initials: LS
authors.lastname: Hodge
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ziesmer
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006689:Hodgkin Disease / Q000097:blood* / Q000473:pathology / Q000628:therapy; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D015375:Receptors, Interleukin-2 / Q000097:blood*
chemical_list: D015850:Interleukin-6; D015375:Receptors, Interleukin-2