Abstract
Systemic mastocytosis (SM) is frequently associated with eosinophilia. To examine its prevalence and clinical impact in all WHO classification-based subcategories, we analyzed eosinophil counts in 2350 mastocytosis patients using the dataset of the European Competence Network on Mastocytosis. Ninety percent of patients had normal eosinophil counts, 6.8% mild eosinophilia (0.5–1.5 × 109/l), and 3.1% hypereosinophilia (HE; >1.5 × 109/l). Eosinophilia/HE were mainly present in patients with advanced SM (17%/19%), and only rarely recorded in patients with indolent and smoldering SM (5%/1%), and some patients with cutaneous mastocytosis. The eosinophil count correlated with organomegaly, dysmyelopoiesis, and the WHO classification, but not with mediator-related symptoms or allergy. Eosinophilia at diagnosis had a strong prognostic impact (p < 0.0001) on overall survival (OS) and progression-free survival (PFS), with a 10-year OS of 19% for patients with HE, 70% for those with mild eosinophilia, and 88% for patients with normal eosinophil counts. In 89% of patients with follow-up data (n = 1430, censored at start of cytoreductive therapy), eosinophils remained stable. In those with changing eosinophil counts (increase/decrease or mixed pattern), OS and PFS were inferior compared with patients with stable eosinophil counts. In conclusion, eosinophilia and HE are more prevalent in advanced SM and are predictors of a worse outcome.
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Acknowledgements
This work was supported by the Austrian Science Fund (FWF), SFB grants F4701-B20 and F4704-B20 (to PV), by the Deutsche Forschungsgemeinschaft (DFG, RA 2838 to AI), by the Koeln Fortune Program, Faculty of Medicine, University of Cologne (216/2016 to AI), and by the ´Charles and Ann Johnson Foundation’ (to JG). CB is supported by the Clinical Research Fund of the University Hospital Leuven. We thank all technicians, study coordinators, study nurses, and colleagues for data entry into the registry system. Our special thanks for statistical help to Michael Kundi, and to data management and data controlling go to: Susanne Herndlhofer, Nadja Jaekel, Hassiba Bouktit, Gabriele Stefanzl, Hana Škabrahová, Gulkan Ozkan, Tarik Tiryaki, Nicole Cabral do O, Deborah Christen, Anne Simonowski, Cecilia Spina, Agnes Bretterklieber, Orsolya Pilikta, Lilla Kurunci, Kerstin Hamberg-Levedahl, Pietro Benvenuti, Gregor Verhoef, Peter Vandenberghe, Dominique Bullens, Anna Van Hoolst, Nele Philips, Toon Ieven, Gülkan Özkan, and Stephanie Pulfer.
Author contributions
HCK-N had the conceptual idea, helped with the analyses, and wrote the paper. WRS did all analyses, was responsible for data collection and correction in the ECNM database, designed all figures, and cowrote the article. AI and KH did the initial analyses and corrected the final version of the manuscript. BvA and LRFS were helpful in discussions and helped with entry of patient data and corrected the final version of the manuscript. AG, MN, ML, LS, RZ, PB, CP, CE, LM, KS, NvB, RP, MT, AR, JS, MJ, FC, ABF, KB, AZ, DF, AK, ASY, MD, MM, HH, JP, VS, EA, DN, CB, JV, LM, VK, OLy, TJ, OH, JR, MA, and JG contributed with patient data and corrected the final version of the manuscript. PV contributed to the study plan, cowrote the manuscript, and supervised the ECNM database.
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HCK-N: institutional financial support from Novartis to perform a phase II trial with midostaurin. WRS: honoraria from Novartis, Pfizer, AbbVie, Daiichi Sankyo, Amgen, Thermo Fisher, Deciphera, Incyte, Celgene, and Jazz. BvA: financial support from Novartis for research and advisory boards. KH: research grant: Euroimmun Lectures, and consulting: ALK, Blueprint, Deciphera, and Novartis. CE, DF, and JR: advisory board Novartis. KS: travel expenses from Novartis. NvB: institutional financial support from Novartis. MT: advisory board/honoraria: Deciphera and Novartis. JP: funding to support conduct of clinical trial: Blueprint Medicines and Deciphera; advisory board/honoraria: Blueprint Medicines and Novartis. OH: research funding support from AB science and Novartis. Advisory board of AB science. JG: funding to support conduct of clinical trial: Blueprint Medicines and Deciphera; advisory board/honoraria: Blueprint Medicines, Deciphera, and Allakos. VS is a senior clinical researcher of the Research Foundation Flanders/Fonds Wetenschappelijk Onderzoek (FWO: 1804518N).
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Kluin-Nelemans, H.C., Reiter, A., Illerhaus, A. et al. Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry. Leukemia 34, 1090–1101 (2020). https://doi.org/10.1038/s41375-019-0632-4
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DOI: https://doi.org/10.1038/s41375-019-0632-4
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