Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis

Axel Rüfer; Henning Nilius; Olivier Hermine; Marek Niedoszytko; Joanne N G Oude Elberink; Patrizia Bonadonna; Khalid Shoumariyeh; Theo Gulen; Karin Hartmann; Vito Sabato; Irena Angelova-Fischer; Daniel Baffoe; Deborah Christen; Anna Belloni Fortina; Christine Breynaert; Knut Brockow; Nikolas von Bubnoff; Horia Bumbea; Paul van Daele; Michael Doubek; Ingunn Dybedal; Chiara Elena; Christos Fokoloros; Aleksandra Górska; Marc Heizmann; Madlen Jentzsch; Saskia Klein; Johannes Lübke; Mattias Mattsson; André Mulder; Jens Panse; Tanja Daniela Schug; Mariarita Sciumè; Alex Stefan; Marlena Sztormowska; Judit Várkonyi; Friederike Wortmann; Akif Selim Yavuz; Martina Sperr; Jason Gotlib; Andreas Reiter; Massimo Triggiani; Wolfgang R Sperr; Peter Valent

doi:10.1038/s41375-024-02504-3

Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis

Leukemia. 2025 Jan 15. doi: 10.1038/s41375-024-02504-3. Online ahead of print.

Authors

Axel Rüfer¹, Henning Nilius², Olivier Hermine³, Marek Niedoszytko⁴, Joanne N G Oude Elberink⁵, Patrizia Bonadonna⁶, Khalid Shoumariyeh^{7

8}, Theo Gulen⁹, Karin Hartmann¹⁰, Vito Sabato¹¹, Irena Angelova-Fischer¹², Daniel Baffoe¹³, Deborah Christen¹⁴, Anna Belloni Fortina¹⁵, Christine Breynaert¹⁶, Knut Brockow¹⁷, Nikolas von Bubnoff¹⁸, Horia Bumbea¹⁹, Paul van Daele²⁰, Michael Doubek²¹, Ingunn Dybedal¹³, Chiara Elena²², Christos Fokoloros²³, Aleksandra Górska⁴, Marc Heizmann²⁴, Madlen Jentzsch²⁵, Saskia Klein⁵, Johannes Lübke²⁶, Mattias Mattsson²⁷, André Mulder⁵, Jens Panse¹⁴, Tanja Daniela Schug²⁸, Mariarita Sciumè²⁹, Alex Stefan³⁰, Marlena Sztormowska⁴, Judit Várkonyi³¹, Friederike Wortmann¹⁸, Akif Selim Yavuz³², Martina Sperr³³, Jason Gotlib^{34

35}, Andreas Reiter²⁶, Massimo Triggiani³⁶, Wolfgang R Sperr^{33

37}, Peter Valent^{33

37}

Affiliations

¹ Department of Hematology, Luzerner Kantonsspital, University of Luzern, Luzern, Switzerland. [email protected].
² Department of Clinical Chemistry, University Hospital Bern, Inselspital, Bern, Switzerland.
³ Hôpital Necker, Imagine Institute INSERM U1163, University of Sorbonne Paris Cité, Centre national de référence des mastocytoses, Paris, France.
⁴ Department of Allergology, Medical University of Gdansk, Gdansk, Poland.
⁵ University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Allergy Unit, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy.
⁷ Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany.
⁸ German Cancer Consortium (DKTK), Partner Site Freiburg, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁹ Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Huddinge, Stockholm; and Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Universitätsspital Basel, Basel, Switzerland.
¹¹ Universiteit Antwerpen, Campus Drie Eiken, Antwerp, Belgium.
¹² Klinik für Dermatologie und Venerologie, Kepler Universitätsklinikum, Linz, Austria.
¹³ Departments of Hematology and Pharmacology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
¹⁴ Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany & Department of Haematology, Oncology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
¹⁵ Pediatric Dermatology, Internal Medicine, Azienda Ospedaliera, Università di Padova, Padova, Italy.
¹⁶ KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group and MASTeL, UZ Leuven, Leuven, Belgium.
¹⁷ Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein; Technische Universität München, München, Germany.
¹⁸ Department for Hematology and Oncology, Universitätsklinikum Schleswig-Holstein and University Cancer Center Schleswig-Holstein, Lübeck, Germany.
¹⁹ Department of Hematology, Bone Marrow Transplant Unit, Carol Davila University of Medicine and Pharmacy, Emergency University Hospital, Bucharest, Romania.
²⁰ Department of Internal Medicine, Erasmus University Rotterdam, Rotterdam, The Netherlands.
²¹ Brno University Hospital, Brno, Czech Republic.
²² Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy.
²³ Mastocytosis Center, "Attikon" University Hospital of Athens, Athens, Greece.
²⁴ Kantonsspital Aarau AG, Medizinische Universitätsklinik, Hämatologie, Aarau, Switzerland.
²⁵ Medical Clinic I, Universitätsklinikum Leipzig AöR, Leipzig, Germany.
²⁶ Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany.
²⁷ Department of Hematology, Uppsala University Hospital, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
²⁸ Universitätsklinik für Dermatologie und Venerologie, Medical University of Graz, Graz, Austria.
²⁹ S.C. Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
³⁰ Klinik für Innere Medizin 3 - Schwerpunkt Hämatologie und Onkologie, Kepler Universitätsklinikum, Linz, Austria.
³¹ Department of Hematology, Semmelweis University, Budapest, Hungary.
³² Division of Hematology, Istanbul Medical School, University of Istanbul, Istanbul, Turkey.
³³ Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
³⁴ University of California, San Francisco, CA, USA.
³⁵ Stanford Cancer Institute/Stanford University School of Medicine, Stanford, CA, USA.
³⁶ Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
³⁷ Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.

PMID: 39815050
DOI: 10.1038/s41375-024-02504-3

Abstract

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders. The percentage of CD2^-, CD25⁺ and/or CD30⁺ MC was considerably lower in patients with indolent SM compared to patients with advanced SM, including aggressive SM and MC leukemia. Whereas CD25 and CD30 expression in MC could not be associated with prognosis, we found that lack of CD2 expression in MC is associated with a significantly reduced overall survival (OS) in patients with SM (p < 0.0001). Lack of CD2 was also associated with the presence of extramedullary involvement affecting the spleen, liver, and/or lymph nodes (odds ratio 2.63 compared to SM with CD2⁺ MC). Together, lack of CD2 expression in MC is a prognostic marker and indicator of reduced OS and extramedullary disease expansion in patients with SM.