Gene expression-based outcome prediction in advanced stage classical Hodgkin lymphoma treated with BEACOPP

Jachimowicz, Ron D.; Klapper, Wolfram; Glehr, Gunther; Müller, Horst; Haverkamp, Heinz; Thorns, Christoph; Hansmann, Martin Leo; Möller, Peter; Stein, Harald; Rehberg, Thorsten; Tresckow, Bastian von; Reinhardt, Hans Christian; Borchmann, Peter; Chan, Fong Chun; Spang, Rainer; Scott, David W.; Engert, Andreas; Altenbuchinger, Michael; Rosenwald, Andreas

doi:10.1038/s41375-021-01314-1

Cited by 10 publications

(9 citation statements)

References 13 publications

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“…1,2 GEP studies have been reported in CHL with the goal to predict outcomes after standard-of-care treatments. 237,238 Overall, testing at diagnosis in adult CHL is disappointing with a lack of validation in treatment-intense 239 and response-adapted 240,241 trials. Outcome prediction models in relapsed CHL and pediatric patients await further validation.…”

Section: Pediatric B-cell Lymphomasmentioning

confidence: 99%

Genomic profiling for clinical decision making in lymphoid neoplasms

Leval

Alizadeh

Bergsagel

et al. 2022

Blood

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With the introduction of large-scale molecular profiling methods and high-throughput sequencing technologies, the genomic features of most lymphoid neoplasms have been characterized at an unprecedented scale. While the principles for the classification and diagnosis of these disorders, founded on a multidimensional definition of disease entities, have been consolidated over the past 25 years, novel genomic data have markedly enhanced our understanding of lymphomagenesis and enriched the description of disease entities at the molecular level. Yet the current diagnosis of lymphoid tumors is largely based on morphological assessment and immunophenotyping, with only few entities being defined by genomic criteria. This paper, which accompanies the International Consensus Classification of mature lymphoid neoplasms, will address how established assays and newly developed technologies for molecular testing already complement clinical diagnoses and provide a novel lens on disease classification. More specifically, their contributions to diagnosis refinement, risk stratification and therapy prediction will be considered for the main categories of lymphoid neoplasms. The potential of whole-genome sequencing, circulating tumor DNA analyses, single-cell analyses and epigenetic profiling will be discussed, as these will likely become important future tools for implementing precision medicine approaches in clinical decision-making for patients with lymphoid malignancies.

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Section: Pediatric B-cell Lymphomasmentioning

confidence: 99%

Genomic profiling for clinical decision making in lymphoid neoplasms

Leval

Alizadeh

Bergsagel

et al. 2022

Blood

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“…Thus, we additionally analyzed HLA expression on HRSCs in a cohort of advanced‐stage HL treated with conventional chemotherapy (BEACOPP‐based) in the GHSG phase III trials HD12 21 and HD15, 22 for which gene expression and WSI analysis data have already been published. 3 , 23 Details on these cohorts including their unbiased nature with respect to the whole study cohort of the clinical trials have been described previously. 3 , 23 …”

Section: Methodsmentioning

confidence: 99%

Human leukocyte antigen (HLA) class I expression on Hodgkin–Reed–Sternberg cells is an EBV‐independent major determinant of microenvironment composition in classic Hodgkin lymphoma

Müller‐Meinhard,

Seifert,

Grund

et al. 2024

HemaSphere

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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.

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“…This result highlighted how different therapeutic approaches may require the necessity to develop different predictors for risk assessment [123].…”

Section: Gep Signature and Tmementioning

confidence: 99%

Hodgkin Lymphoma: A Special Microenvironment

Opinto

Agostinelli

Ciavarella

et al. 2021

JCM

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Classical Hodgkn’s lymphoma (cHL) is one of the most particular lymphomas for the few tumor cells surrounded by an inflammatory microenvironment. Reed-Sternberg (RS) and Hodgkin (H) cells reprogram and evade antitumor mechanisms of the normal cells present in the microenvironment. The cells of microenvironment are essential for growth and survival of the RS/H cells and are recruited through the effect of cytokines/chemokines. We summarize recent advances in gene expression profiling (GEP) analysis applied to study microenvironment component in cHL. We also describe the main therapies that target not only the neoplastic cells but also the cellular components of the background.

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Gene expression-based outcome prediction in advanced stage classical Hodgkin lymphoma treated with BEACOPP

Cited by 10 publications

References 13 publications

Genomic profiling for clinical decision making in lymphoid neoplasms

Genomic profiling for clinical decision making in lymphoid neoplasms

Human leukocyte antigen (HLA) class I expression on Hodgkin–Reed–Sternberg cells is an EBV‐independent major determinant of microenvironment composition in classic Hodgkin lymphoma

Hodgkin Lymphoma: A Special Microenvironment

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