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Abstract Background Classical Hodgkin Lymphoma (cHL) represents the majority of HLs with good prognosis The prognostic significance of tumor-associated macrophages (TAM) and Topoisomerase II alpha (Topo IIÜ) in adult cHL remains controversial. The aim of this study is to evaluate the association of CD68 positive (TAM) and Topo IIÜ on clinical outcome of adult patient with advanced stage cHL Patients and methods: During the period between 2012 to 2017, conducted at Medical Oncology Departments of National Cancer Institute, Cairo University and Zagazig University Hospitals Immuno-histochemical (IHC) analysis was performed to stain TAM with anti-CD68 clones (KPI &PGM1) and (IHC) stains Topo IIÜ with anti-CD30 antibodies Results: This study included (82) patients with advanced stage cHL, males to females’ ratio was (1:1), median age was 30.5 years range (18-60 years), All patients received ABVD High CD68+TAM was associated with age{u2265}45Y (P=0.05) and histological subtype (P=0.001), Adverse disease-free survival (DFS) (at cutoff 50%) (P=0.015), But not with overall survival (OS)(P=0.42), High Topo IIÜ expression was associated with histological subtype (P=0.01) and no statistically significant association was detected between Topo IIÜ and OS, DFS |