Serum YKL-40 and Interleukin 6 Levels in Hodgkin Lymphoma

Purpose: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially in nodular sclerosis Hodgkin lymphoma. Experimental Design: We analyzed Danish and Swedish patients with incident Hodgkin lymphoma (N = 470) and population controls from Denmark (n = 245 for YKL-40; n = 348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed by linear regression, adjusting for age and sex. Results: Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold; both, P < 0.0001). In pretreatment samples from pretreatment Hodgkin lymphoma patients (n = 176), levels were correlated with more advanced stages (P-trend, 0.0001 for YKL-40 and 0.013 for IL-6) and in those with B symptoms; however, levels were similar in nodular sclerosis and mixed cellularity subtypes, by EBV status, and in younger (05 years old) an older patients. Patients tested soon after treatment onset had significantly lower levels than pretreatment patients; however, even 6 months after treatment onset, serum YKL-40 and IL-6 levels remained significantly increased compared with controls. In patients who died (n = 12), pretreatment levels for YKL-40 and IL-6 were higher than in survivors, although not statistically significantly. Conclusions: Serum YKL-40 and IL-6 levels were increased in untreated Hodgkin lymphoma patients and those with more advanced stages but did not differ significantly by Hodgkin lymphoma histology. Following treatment, serum levels were significantly lower.