title: Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma.
abstract: Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n = 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy. Correlations with outcome in chemotherapy treated patients were further examined in a separate cohort of 183 South West Oncology Group (SWOG) patients and all patients were then included in a meta-analysis. Six cytokines were associated with outcome in the Molecular Epidemiology Resource (MER) after adjusting for the FL international prognostic index. In patients who were observed or treated with rituximab alone, increased serum IL-12 and interleukin 1 receptor antagonist (IL-1RA) (P = .005 and .02) were associated with a shorter event-free survival. In patients receiving chemotherapy, hepatocyte growth factor, IL-8, IL-1RA, and CXCL9 (P = .015, .048, .004, and .0005) predicted a shorter EFS. When the MER chemotherapy treated patients and SWOG patients were combined in a meta-analysis, IL-2R, IL-1RA, and CXCL9 (P = .013, .042, and .0012) were associated with a poor EFS.
authors.affiliation: Division of Hematology.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Mir
authors.affiliation: Biomedical Statistics and Informatics, and.
authors.forename: Matthew J
authors.identifier: http://orcid.org/0000-0002-1867-0526
authors.initials: MJ
authors.lastname: Maurer
authors.affiliation: Division of Hematology.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ziesmer
authors.affiliation: Biomedical Statistics and Informatics, and.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.affiliation: Division of Hematology.
authors.forename: Thomas
authors.initials: T
authors.lastname: Habermann
authors.affiliation: Division of Hematopathology, Mayo Clinic, Rochester, MN;
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.affiliation: College of Medicine, University of Iowa, Iowa City, IA;
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.affiliation: College of Medicine, University of Iowa, Iowa City, IA;
authors.forename: Sergei
authors.initials: S
authors.lastname: Syrbu
authors.affiliation: Division of Hematology.
authors.forename: Thomas
authors.initials: T
authors.lastname: Witzig
authors.affiliation: Wilmot Cancer Institute, University of Rochester, Rochester, NY;
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.affiliation: Fred Hutchinson Cancer Center/South West Oncology Group Statistical Center, Seattle, WA; and.
authors.forename: Oliver
authors.initials: O
authors.lastname: Press
authors.affiliation: Fred Hutchinson Cancer Center/South West Oncology Group Statistical Center, Seattle, WA; and.
authors.forename: Michael
authors.initials: M
authors.lastname: LeBlanc
authors.affiliation: Division of Epidemiology, Mayo Clinic, Rochester, MN.
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.affiliation: Division of Hematology.
authors.forename: Anne
authors.initials: A
authors.lastname: Novak
authors.affiliation: Division of Hematology.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D054370:Chemokine CXCL9 / Q000097:blood*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D008224:Lymphoma, Follicular / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015375:Receptors, Interleukin-2 / Q000097:blood*; D000069283:Rituximab; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D054370:Chemokine CXCL9; D007155:Immunologic Factors; D053590:Interleukin 1 Receptor Antagonist Protein; D015375:Receptors, Interleukin-2; D000069283:Rituximab