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Introduction: Hodgkin lymphoma (HL) is unusual among malignancies, with inflammation playing such a prominent role in its pathogenesis. S100A8/A9 (calprotectin) is a heterodimeric protein, which has a role in the inflammatory response and oncogenesis. In this study in HL patients, the correlation between serum S100A8/A9 levels and treatment responses was investigated along with whether this marker is correlated with other inflammatory markers., Materials and Methods: Thirty-three HL patients and 20 healthy volunteers were included. Demographic and clinical characteristics were recorded. Calprotectin levels were measured with Human S100A8/A9 Heterodimer Quantikine ELISA kit. Calprotectin levels were measured twice in patients, before and after treatment, and once in the control group. Treatment responses were evaluated with positron emission tomography-computed tomography (PET-CT)., Results: The mean age of patients was 44.3 ± 18.1 (66.3% male). The median (IQR) values of S100A8/A9 before and after treatment in the patient group were 4.98 (2.6-7.8) and 1.87 (1.1-4.8)µg/mL. Median (IQR) S100A8/A9 concentration in the control group was 1.41 (0.98-2.73)µg/mL. In patients, pretreatment values were significantly higher than in controls (P < .001). However, median values of patients after treatment and controls were similar. Patient median S100A8/A9 levels were significantly lower post-treatment compared with pretreatment values (P = .001). When inflammatory markers were examined within groups, no relationship was found between markers. In ROC analysis, a S100A8/A9 cutoff value of ≥3.31µg/mL accurately discriminated end-of-treatment PET positivity (AUC = 0.78; 95% CI 0.58-0.98; accuracy = 76.2%)., Conclusion: S100A8/A9 may be a potential biomarker for treatment response in HL independent of inflammation. This is the first study to investigate and show this finding. However, further large-scale studies are still required., (© 2021 John Wiley & Sons Ltd.)