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Multicenter Study
. 2025 Mar;39(3):675-683.
doi: 10.1038/s41375-024-02504-3. Epub 2025 Jan 15.

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  1 , Henning Nilius  2 , Olivier Hermine  3 , Marek Niedoszytko  4 , Joanne N G Oude Elberink  5 , Patrizia Bonadonna  6 , Khalid Shoumariyeh  7   8 , Theo Gulen  9 , Karin Hartmann  10 , Vito Sabato  11 , Irena Angelova-Fischer  12 , Daniel Baffoe  13 , Deborah Christen  14 , Anna Belloni Fortina  15 , Christine Breynaert  16 , Knut Brockow  17 , Nikolas von Bubnoff  18 , Horia Bumbea  19 , Paul van Daele  20 , Michael Doubek  21 , Ingunn Dybedal  13 , Chiara Elena  22 , Christos Fokoloros  23 , Aleksandra Górska  4 , Marc Heizmann  24 , Madlen Jentzsch  25 , Saskia Klein  5 , Johannes Lübke  26 , Mattias Mattsson  27 , André Mulder  5 , Jens Panse  14 , Tanja Daniela Schug  28 , Mariarita Sciumè  29 , Alex Stefan  30 , Marlena Sztormowska  4 , Judit Várkonyi  31 , Friederike Wortmann  18 , Akif Selim Yavuz  32 , Martina Sperr  33 , Jason Gotlib  34   35 , Andreas Reiter  26 , Massimo Triggiani  36 , Wolfgang R Sperr  33   37 , Peter Valent  33   37
Affiliations
Multicenter Study

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 et al. Leukemia. 2025 Mar.

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.

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Conflict of interest statement

Competing interests: Conflicts of interest declared by the co-autors: Axel Rüfer: Advisory boards: Blueprint Medicines; Oliver Hermine: Research funding support from AB science and Novartis. Advisory board of AB science; Patrizia Bonadonna: Honoraria: Blueprint Medicines; Karin Hartmann: Lectures/consultancy: ALK, Allergopharma, BioCryst, Blueprint Medicines, Cogent, KalVista, Leo, Menarini, Novartis, Pfizer, Sanofi, Takeda, Thermo Fisher; Vito Sabato: Advisory boards: Blueprint Medicines, Cogent, Novartis, Telios. Honoraria: Thermo Fisher; Knut Brockow: Advisory board and honoraria: Blueprint Medicines; Nikolas von Bubnoff: Honoraria Novartis, Takeda, Astra Zeneca, Janssen-Cilag; Paul van Daele: Lectures/consultancy: Novartis, involved in clinical trials for Cogent Biosciences and Blueprint Medicines; Ingunn Dybedal: Advisory board and honoraria: Blueprint Medicines; Chiara Elena: Advisory board and honoraria: Blueprint Medicines, Gilead; Marc Heizmann: Advisory board and honoraria: Novartis; Jens Panse: Advisory board and honoraria: Blueprint Medicines, Novartis, Deciphera; Friederike Wortmann: Advisory board and honoraria: Blueprint Medicines, Novartis, Pierre Fabre, Abbvie; Jason Gotlib: Research Grant (funds for administration of clinical trials): Novartis, Blueprint Medicines, Deciphera, Cogent Biosciences; Advisory Board and Honoraria: Blueprint Medicines, Novartis, Deciphera, Cogent Biosciences; Reimbursement of travel expenses: Novartis, Blueprint Medicines; Andreas Reiter: Honoraria: Novartis, Blueprint Medicines, Incyte, Celgene/Bristol Myers Squibb, AOP Orphan Pharmaceuticals, GlaxoSmithKline, AbbVie; Consulting or Advisory Role: Novartis, Blueprint Medicines, Incyte, Celgene/Bristol Myers Squibb, AOP Orphan Pharmaceuticals, AbbVie; Massimo Triggiani: Advisory Board and Honoraria: Blueprint Medicines, Novartis; Wolfgang R. Sperr: Honoraria from AbbVie, Astellas, Blueprint, BMS-Celgene, Daiichi Sankyo, Deciphera, Incyte, Jazz Pharmaceuticals, Laboratoires Delbert, Novartis, Otsuka, Pfizer, Servier, Stemline, Thermo Fisher; Peter Valent: 1. Advisory board - honoraria: AOP Orphan, Blueprint, Cogent, Delbert, Incyte, Novartis, PentaBase, Pfizer, Stemline. 2. Research grant: AOP Orphan, Pfizer. The remaining co-authors declared no conflict of interest. Ethics approval and consent to participate: All methods were performed in accordance with the relevant guidelines and regulations. The ECNM registry study was approved by the responsible local ethics committee of each participating ECNM center. Written informed consent was obtained from all patients included in the ECNM registry.

Figures

Fig. 1
Fig. 1. Distribution of different patterns of expression of CD2 and/or CD25 in/on MC in various groups of patients.
Expression of CD2 and CD25 in or on bone marrow MC was determined by flow cytometry and/or immunohistochemistry in 2225 patients (44.25%) with mastocytosis and available results of CD2 and CD25 expression, including cutaneous mastocytosis (CM, n = 221), indolent systemic mastocytosis (ISM, n = 1595), smoldering systemic mastocytosis (SSM, n = 48), and advanced systemic mastocytosis (advSM, n = 313). In most patients with ISM, MC expressed both CD2 and CD25. However, whereas in a considerable number of patients with SSM and advSM, MC did not express CD2 but still expressed CD25. In very few patients with SM, MC were found to lack CD2 and CD25. MC mast cells.
Fig. 2
Fig. 2. Overall survival (OS) in patients with SM stratified by CD2 and CD25 expression patterns in MC.
OS was analyzed in a univariate analysis in 1183 patients with SM in whom FU and survival data were reported and results by flow cytometry and/or immunohistochemistry for CD2 expression and CD25 expression on/in MC were available. Four groups of patients were examined based on the pattern of CD2 and CD25 expression on/in MC: CD2-/CD25+ MC, CD2+/CD25+ MC, CD2+/CD25- MC; and CD2-/CD25- MC. The probability of OS in these 4 groups of patients was determined according to the method of Kaplan and Meier. Patients with CD2-negative MC expressing CD25 had a significantly reduced OS compared to patients with MC expressing both, CD2 and CD25. Patients with CD2-negative MC had a significantly shorter OS compared to patients in whom MC expressed CD2 without co-expressing CD25 (p < 0.0001). The p value refers to the comparison of all survival curves as assessed by log-rank test. SM systemic mastocytosis, FU follow-up, MC mast cells.
Fig. 3
Fig. 3. Percentage of patients with SM and extramedullary involvement according to the CD2 expression status in MC.
The two bars reflect the percentage of patients with SM according to the CD2 expression status in MC. In SM patients with CD2-negative MC, 31.9% had extramedullary involvement, whereas in SM patients with CD2-positive MC extramedullary involvement was only found in 14.9%. This difference was statistically significant (p < 0.001). SM systemic mastocytosis, MC mast cells.
Fig. 4
Fig. 4. Distribution of different patterns of expression of CD2, CD25 and CD30 in/on MC in various groups of patients.
Expression of CD2, CD25, and CD30 in or on bone marrow MC was determined by flow cytometry and/or immunohistochemistry in 506 patients (10.95%) with mastocytosis, including cutaneous mastocytosis (CM, n = 42), “mastocytosis in the skin” (MIS, n = 10), indolent systemic mastocytosis (ISM, n = 364), smoldering systemic mastocytosis (SSM, n = 13), and advanced systemic mastocytosis (advSM, n = 77). In patients with ISM, MC expressed both CD2 and CD25, with or without CD30 expression, in a considerably higher number compared to patients with advSM. However, in patients with ISM there was a lower percentage of patients not expressing CD2 but still expressing CD25 and CD30, compared to SSM and advSM. In very few patients with SM, MC were found to lack CD2 and CD25, regardless of CD30 expression. MC mast cells.
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