Prognostic Significance of Pretreatment Serum Cytokines in Classical Hodgkin Lymphoma

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 coul...

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Bibliographic Details
Published in:Clinical cancer research 2013-12, Vol.19 (24), p.6812-6819
Main Authors: MARRI, Preethi Reddy, HODGE, Lucy S, MAURER, Matthew J, ZIESMER, Steven C, SLAGER, Susan L, HABERMANN, Thomas M, LINK, Brian K, CERHAN, James R, NOVAK, Anne J, ANSELL, Stephen M
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic agents
Biological and medical sciences
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic - genetics
Hematologic and hematopoietic diseases
Hodgkin Disease - blood
Hodgkin Disease - pathology
Hodgkin Disease - therapy
Humans
Interleukin-6 - blood
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Middle Aged
Neoplasm Recurrence, Local - blood
Neoplasm Recurrence, Local - pathology
Neoplasm Recurrence, Local - therapy
Neoplasm Staging
Pharmacology. Drug treatments
Prognosis
Proportional Hazards Models
Receptors, Interleukin-2 - blood
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Summary: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. 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. 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. 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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.ccr-13-1879