AbstractImmunohistochemical markers are associated with treatment outcome in adults with classical Hodgkin Lymphoma (cHL). Studies in children are scarce and inconsistent. We investigated in 67 children with cHL, whether the expression of CD15, CD30, PAX5, PD-1, PD-L1, CD68, CD163 and TARC is associated with the event-free survival (EFS) and the interim remission status. Low expression of PD-L1 was significantly associated with complete remission at interim PET-scan. There was no association between marker expression and EFS. Our data suggest a difference between pediatric and adult cHL. This underlies the importance of future research into specific molecular drivers in pediatric cHL.
IntroductionClassical Hodgkin lymphoma (cHL) contains a notably small amount of 0.1-10% malignant Hodgkin and Reed-Sternberg (HRS) cells, surrounded by inflammatory cells. These cells produce different cytokines and chemokines, maintaining a specific tumor microenvironment (TME) in which the HRS cells can thrive 1,2. There is a strong variation among individual patients in the frequency and distribution of HRS cells and the TME 3. These variations may be used to identify prognostic markers in pediatric patients to develop risk-adapted treatment strategies, leading to better outcome and less treatment-related toxicities 1,2. Furthermore, these markers could be new treatment targets. Multiple studies have demonstrated that the presence of certain immune cell types and immunohistochemical markers in the TME and on HRS cells is associated with treatment outcome 4-7. However, most studies have been performed in adult patients, and studies based on pediatric populations are scarce and inconsistent 8-10. Previous studies have shown differences in TME composition, PD-L1 expression, and the role of Epstein Barr Virus (EBV) between pediatric and adult cHL patients 10-14. Therefore, it is uncertain whether outcomes of studies in adults with cHL are applicable to children with cHL.
Therefore, we investigated the prognostic value of eight different immunohistochemical markers in pediatric cHL. PD-1, PD-L1, CD15, CD30, CD68 and CD163 have previously been analyzed in pediatric studies and show conflicting outcomes 8-10,15. PAX5 and TARC were chosen based on their prognostic impact in adult studies6,16,17.