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Ferrata Storti Foundation
Haematologica 2021 Volume 106(6):1684-1692
Hodgkin Lymphoma
Whole-slide image analysis of the tumor microenvironment identifies low B-cell content as a predictor of adverse outcome in patients with advanced-stage classical Hodgkin lymphoma treated with BEACOPP
Ron Daniel Jachimowicz,1,2,3* Luise Pieper,4* Sarah Reinke,4,* Artur Gontarewicz,4,*
Annette Plütschow,1 Heinz Haverkamp,1 Leonie Frauenfeld,5 Falko Fend,5 Mathis
5467 Overkamp, Franziska Jochims, Christoph Thorns, Martin Leo Hansmann, Peter
8 9 10 2,3,11,12 Möller, Andreas Rosenwald, Harald Stein, Hans Christian Reinhardt,
Peter Borchmann,1,3 Bastian von Tresckow,1,3 Andreas Engert1,3 and Wolfram Klapper4
1University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Cologne; German Hodgkin Study Group, Cologne; 2Else Kröner Forschungskolleg Clonal Evolution in Cancer, University Hospital Cologne, Cologne; 3University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf, Cologne; 4Department of Pathology, Hematopathology Section, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel; 518Department of Pathology, University of Tübingen, Tübingen; 6Department of Pathology, University Hospital Schleswig- Holstein, University of Lübeck, Lübeck; 7Department of Pathology, University Hospital Frankfurt, Frankfurt; 8Department of Pathology, University Hospital Ulm, Ulm; 9Institute of Pathology, University of Würzburg, and Comprehensive Cancer Center Mainfranken, Würzburg; 10Pathodiagnostik, Berlin; 11Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, Cologne and 12Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
ABSTRACT
Asubset of patients with advanced-stage classical Hodgkin lym- phoma (cHL) relapse or progress following standard treatment. Given their dismal prognosis, identifying this group of patients upfront represents an important medical need. While prior research has identified characteristics of the tumor microenvironment, which are associated with cHL outcomes, biomarkers that are developed and vali- dated in this high-risk group are still lacking. Here, we applied whole- slide image analysis (WSI), a quantitative, large-scale assessment of tumor composition that utilizes conventional histopathology slides. We conducted WSI on pre-treatment biopsies from 340 patients with advanced-stage cHL enrolled in the HD12 and HD15 trials of the German Hodgkin Study Group (GHSG), and tested our results in a validation cohort of 147 advanced-stage cHL patients within the GHSG HD18 trial. All patients were treated with BEACOPP-based regimens. By quantifying T cells, B cells, Hodgkin and Reed-Sternberg cells and macrophages with WSI, 80% of all cells in the tumor tissue were identified. Crucially, low B-cell count was associated with significantly reduced progression-free survival and overall survival, while the content of T cells, macrophages and Hodgkin and Reed-Sternberg cells was not associated with the risk of progression or relapse in the study cohort. We further validated low B- cell content as a prognostic factor for progression-free survival and over- all survival in the validation cohort and demonstrated the good inter- observer agreement of WSI. WSI may represent a key tool for risk strat- ification of advanced-stage cHL and can easily be added to the standard diagnostic histopathology work-up.
*RDJ, LP, SR and AG contributed equally as co-first authors.
Correspondence:
RON D. JACHIMOWICZ
ron.jachimowicz@uk-koeln.de
WOLFRAM KLAPPER
wklapper@path.uni-kiel.de
Received: December12,2019. Accepted: April 29, 2020. Pre-published: May 7, 2020.
https://doi.org/10.3324/haematol.2019.243287
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