Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry - PubMed (original) (raw)

. 2020 Apr;34(4):1090-1101.

doi: 10.1038/s41375-019-0632-4. Epub 2019 Nov 18.

Andreas Reiter 2, Anja Illerhaus 3, Bjorn van Anrooij 4 5, Karin Hartmann 3 6, Lambertus F R Span 4, Aleksandra Gorska 7, Marek Niedoszytko 7, Magdalena Lange 8, Luigi Scaffidi 9, Roberta Zanotti 9, Patrizia Bonadonna 10, Cecelia Perkins 11, Chiara Elena 12, Luca Malcovati 12, Khalid Shoumariyeh 13 14, Nikolas von Bubnoff 13 14 15, Roberta Parente 16, Massimo Triggiani 16, Juliana Schwaab 2, Mohamad Jawhar 2, Francesca Caroppo 17, Anna Belloni Fortina 17, Knut Brockow 18, Alexander Zink 18, David Fuchs 19, Alex Kilbertus 20, Akif Selim Yavuz 21, Michael Doubek 22, Mattias Mattsson 23, Hans Hagglund 23, Jens Panse 24, Vito Sabato 25, Elisabeth Aberer 26, Dietger Niederwieser 27 28, Christine Breynaert 29, Judit Várkonyi 30, Vanessa Kennedy 11, Olivier Lortholary 31, Thilo Jakob 32 33 34, Olivier Hermine 35, Julien Rossignol 36, Michel Arock 37, Jason Gotlib 11, Peter Valent 38 39, Wolfgang R Sperr 38 39

Affiliations

Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry

Hanneke C Kluin-Nelemans et al. Leukemia. 2020 Apr.

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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Conflict of interest statement

Conflict of interest 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).

Figures

Fig. 1

Fig. 1

Dot plot representing individual absolute eosinophil counts at diagnosis of mastocytosis. Data from 2350 patients of all WHO cutaneous and systemic mastocytosis subcategories. DCM diffuse cutaneous mastocytosis, MCPM maculopapular cutaneous mastocytosis, MIS mastocytosis in the skin, ISM indolent systemic mastocytosis, SSM smoldering systemic mastocytosis, ASM aggressive systemic mastocytosis, MCL mast cell leukemia, MCS mast cell sarcoma, SM-AHN systemic mastocytosis with an associated hematological neoplasm

Fig. 2

Fig. 2

Survival (overall, progression-free (PFS), and event-free (EFS)) according to the initial absolute numbers of eosinophils at diagnosis analyzed in all patients. For the definition of PFS, patients in the MIS group and patients with mast cell leukemia were not included. Note that for PFS the _Y_-axis is cut at 70%. The p value refers to the comparison of all three survival curves as assessed by log rank test

Fig. 3

Fig. 3

Survival (overall, progression-free (PFS), and event-free (EFS)) according to the initial absolute numbers of eosinophils at diagnosis analyzed only in the patients within the ISM category. Note that in the figure showing PFS data, the _Y_-axis is cut at 70%. The p value refers to the comparison of all three survival curves as assessed by log rank test

Fig. 4

Fig. 4

Survival (overall, progression-free (PFS), and event-free (EFS)) according to the follow-up of the absolute numbers of eosinophils. Not stable in time means that an increase (from normal range to eosinophilia, or from eosinophilia to hypereosinophilia), a decrease, or mixed pattern was observed. For the definition of PFS, patients in the MIS group and patients with mast cell leukemia were not included. Note that for PFS, the _Y_-axis is cut at 40%. The p value refers to the comparison of the survival curves as assessed by log rank test

Fig. 5

Fig. 5

Overall survival of patients who showed decrease, increase, mixed pattern, or no change (stable) of eosinophil counts during follow-up. Data were censored for start cytoreductive therapy or corticosteroids. The p value refers to the comparison of all four survival curves as assessed by log rank test

References

    1. Horny H-P, Akin C, Arber DA, Peterson LC, Tefferi A, Metcalfe DD, et al. Mastocytosis. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2017. pp. 62–9.
    1. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373:163–72. -PubMed
    1. Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O, et al. Advances in the classification and treatment of mastocytosis: current status and outlook toward the future. Cancer Res. 2017;77:1261–70. -PMC -PubMed
    1. Butterfield JH, Ravi A, Pongdee T. Mast cell mediators of significance in clinical practice in mastocytosis. Immunol Allergy Clin North Am. 2018;38:397–410. -PubMed
    1. Arock M, Sotlar K, Akin C, Broesby-Olsen S, Hoermann G, Escribano L, et al. KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis. Leukemia. 2015;29:1223–32. -PMC -PubMed

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