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Hodgkin-Reed-Sternberg cells (HRSCs) in classic Hodgkin Lymphoma (HL) frequently lack expression of human leukocyte antigen class I (HLA-I), considered to hamper activation of cytotoxic T cells in the tumor microenvironment (TME). Here, we demonstrate HLA-I expression on HRSCs to be a strong determinant of TME composition whereas expression of HLA-II was associated with only minor differential gene expression in the TME. In HLA-I-positive HL the HRSC content and expression of CCL17/TARC in HRSCs are low, independent of the presence of Epstein-Barr virus in HRSCs. Additionally, HLA-I-positive HL shows a high content of CD8+ cytotoxic T cells. However, an increased expression of the inhibitory immune checkpoint LAG3 on CD8+ T cells in close proximity to HRSCs is observed. Suggesting interference with cytotoxic activity, we observed an absence of clonally expanded T cells in the TME. While HLA-I-positive HL is not associated with an unfavorable clinical course in our cohorts, they share features with the recently described H2 subtype of HL. Given the major differences in TME composition, immune checkpoint inhibitors may differ in their mechanism of action in HLA-I-positive compared to HLA-I-negative HL., Competing Interests: Dr von Tresckow is an advisor or consultant for Allogene, BMS/Celgene, Cerus, Incyte, IQVIA, Gilead Kite, Lilly, Miltenyi, Novartis, Noscendo, Pentixapharm, Roche, Amgen, Pfizer, Takeda, Merck Sharp & Dohme, and Gilead Kite; has received honoraria from AstraZeneca, BMS, Incyte, Lilly, Novartis, Roche Pharma AG, Takeda, and Merck Sharp & Dohme; reports research funding from Novartis (Inst), Merck Sharp & Dohme (Inst), and Takeda (Inst); and reports travel support from AbbVie, AstraZeneca, Gilead Kite, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, and Novartis all outside the submitted work. Dr P. Borchmann reports grants from BMS during the conduct of the study. Dr Engert reports grants and nonfinancial support from BMS during the conduct of the study, and personal fees from Takeda, BMS, and MSD outside the submitted work. Dr Bröckelmann is an advisor or consultant for BeiGene, BMS, MSD, Stemline, and Takeda, received honoraria from BeiGene, BMS, MSD, Stemline, and Takeda, received travel support from BeiGene, Celgene, and Takeda, and reports research funding from BeiGene (Inst), BMS (Inst), MSD (Inst) and Takeda (Inst). Dr Klapper reports grants from Roche, Amgen, Takeda, Incyte, and Regeneron paid to his institution outside the submitted work. The remaining authors declare no conflicts of interest., (© 2024 The Authors. HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

The rapid evolution of genomic technologies over the last years has led to the development of different methods for the detection, measurement and analysis of cell-free DNA fragments (cfDNA) which are shed into the bloodstream by apoptotic cells and circulate at a low concentration in plasma. In cancer patients, the proportion of tumor-derived cfDNA is defined as circulating tumor DNA. This analysis, commonly known as liquid biopsy, allows to access tumor DNA through a simple blood sampling and therefore without the need of an invasive tissue biopsy. For this reason, this tool may have several clinical applications in terms of diagnosis, prognosis, and monitoring of minimal residual disease. However, there are still several critical issues that need to be resolved. In this review, we will discuss some of the controversies around this method and its potential clinical applications., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

The purpose of this study was to determine whether there is an increased risk of suicide in European Hodgkin Lymphoma (HL) patients compared to the general European population. European HL patients enrolled in the German Hodgkin Study Group (GHSG) HD7 through HD15 studies were analyzed and standardized mortality ratio (SMR) was calculated using suicide mortality rates for the general European population. Case-control analysis was performed to identify characteristics associated with risk of death by suicide. Among 12,202 European HL patients observed for 94,972 person-years, 19 suicides (17 males and 2 females) were identified resulting in a SMR 1.63 (95% CI: 1.01-2.50, p = 0.046). The only characteristic associated with a statistically significant increased risk of suicide was male sex with an odds ratio (OR) 8.42 (95% CI = 1.04-67.85; p = 0.046) on multivariate analysis. These findings were confirmed in an independently analyzed Surveillance, Epidemiology, and End Results Program (SEER) validation dataset. European HL patients have a significantly increased incidence of suicide compared to the general European population. Male HL patients have a greater than 8-fold increased risk of suicide compared to female HL patients. Further study of social risk factors associated with an increased risk of suicide in HL patients is needed., (Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)