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Related Experiment Video

Updated: Jun 11, 2025

Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma
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Circulating Tumor DNA Sequencing for Biologic Classification and Individualized Risk Stratification in Patients With

Jan-Michel Heger1,2,3,4, Laman Mammadova1,2,5, Julia Mattlener1,2,5

  • 1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|September 30, 2024
PubMed
Summary

Researchers identified three Hodgkin lymphoma (HL) subtypes using circulating tumor DNA (ctDNA). This noninvasive method aids in risk stratification and monitoring minimal residual disease (MRD) for personalized HL treatment.

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Area of Science:

  • Hematology
  • Oncology
  • Genomics

Background:

  • Hodgkin lymphoma (HL) presents challenges in treating relapsed/refractory disease and managing long-term treatment toxicities.
  • Current risk stratification relies heavily on tumor burden, as clinical factors have limited discriminatory power.
  • Investigating HL genetics and the tumor microenvironment (TME) is crucial for improving risk assessment.

Purpose of the Study:

  • To identify distinct biological subtypes of Hodgkin lymphoma (HL) using circulating tumor DNA (ctDNA) sequencing.
  • To assess the clinical utility of these subtypes for risk stratification and treatment individualization.
  • To develop a noninvasive method for monitoring minimal residual disease (MRD) in HL patients.

Main Methods:

  • Circulating tumor DNA (ctDNA) sequencing was performed on 243 HL patients from German Hodgkin Study Group trials.
  • Subtypes were independently validated in 96 patients from the EuroNet-PHL-C2 study.
  • Outcome differences were assessed in a 72-patient cohort from the HD21 trial using a refined, clinically feasible assay.

Main Results:

  • Three HL subtypes were identified: inflammatory immune escape HL, virally-driven HL, and oncogene-driven HL.
  • These subtypes exhibit distinct genetic features, TME characteristics, and tumor mutational burden (TMB).
  • A refined assay demonstrated significant progression-free survival differences between subtypes and enabled MRD detection for high-risk relapse prediction.

Conclusions:

  • A clinically feasible, noninvasive method based on ctDNA sequencing is proposed for HL.
  • This approach enables individualized risk stratification and MRD monitoring.
  • The identified subtypes offer new insights into HL biology and potential therapeutic targets.