Prognostic Significance of Pretreatment Serum Cytokines in Classical Hodgkin Lymphoma

Preethi Reddy MARRI; Lucy S HODGE; Matthew J MAURER; Steven C ZIESMER; Susan L SLAGER; Thomas M HABERMANN; Brian K LINK; James R CERHAN; Anne J NOVAK; Stephen M ANSELL

doi:10.1158/1078-0432.CCR-13-1879

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Prognostic Significance of Pretreatment Serum Cytokines in Classical Hodgkin Lymphoma

Journal article

Open access

Peer reviewed

Prognostic Significance of Pretreatment Serum Cytokines in Classical Hodgkin Lymphoma

Preethi Reddy MARRI, Lucy S HODGE, Matthew J MAURER, Steven C ZIESMER, Susan L SLAGER, Thomas M HABERMANN, Brian K LINK, James R CERHAN, Anne J NOVAK and Stephen M ANSELL

Clinical cancer research, Vol.19(24), pp.6812-6819

2013

DOI: 10.1158/1078-0432.CCR-13-1879

PMCID: PMC3867576

PMID: 24141626

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Abstract

Purpose: 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. Experimental design: 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.

Antineoplastic Agents

Hematologic and hematopoietic diseases

Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis

Biological and medical sciences

Medical sciences

Pharmacology. Drug treatments

Details

Title: Subtitle: Prognostic Significance of Pretreatment Serum Cytokines in Classical Hodgkin Lymphoma
Creators: Preethi Reddy MARRI - Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States
Lucy S HODGE - Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States
Matthew J MAURER - Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States
Steven C ZIESMER - Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States
Susan L SLAGER - Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States
Thomas M HABERMANN - Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States
Brian K LINK - Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, Iowa, United States
James R CERHAN - Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States
Anne J NOVAK - Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States
Stephen M ANSELL - Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.19(24), pp.6812-6819
DOI: 10.1158/1078-0432.CCR-13-1879
PMID: 24141626
PMCID: PMC3867576
NLM abbreviation: Clin Cancer Res
ISSN: 1078-0432
eISSN: 1557-3265
Publisher: American Association for Cancer Research
Language: English
Date published: 2013
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
Record Identifier: 9984094557602771

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