Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification

Jakub Trizuljak; Wolfgang R Sperr; Lucie Nekvindová; Hanneke O Elberink; Karoline V Gleixner; Aleksandra Gorska; Magdalena Lange; Karin Hartmann; Anja Illerhaus; Massimiliano Bonifacio; Cecelia Perkins; Chiara Elena; Luca Malcovati; Anna B Fortina; Khalid Shoumariyeh; Mohamad Jawhar; Roberta Zanotti; Patrizia Bonadonna; Francesca Caroppo; Alexander Zink; Massimo Triggiani; Roberta Parente; Nikolas von Bubnoff; Akif S Yavuz; Hans Hägglund; Mattias Mattsson; Jens Panse; Nadja Jäkel; Alex Kilbertus; Olivier Hermine; Michel Arock; David Fuchs; Vito Sabato; Knut Brockow; Agnes Bretterklieber; Marek Niedoszytko; Björn van Anrooij; Andreas Reiter; Jason Gotlib; Hanneke C Kluin-Nelemans; Jiri Mayer; Michael Doubek; Peter Valent

doi:10.1111/all.14248

Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification

Allergy. 2020 Aug;75(8):1927-1938. doi: 10.1111/all.14248. Epub 2020 Mar 16.

Authors

Jakub Trizuljak¹, Wolfgang R Sperr², Lucie Nekvindová³, Hanneke O Elberink⁴, Karoline V Gleixner², Aleksandra Gorska⁵, Magdalena Lange⁶, Karin Hartmann^{7

8}, Anja Illerhaus⁸, Massimiliano Bonifacio⁹, Cecelia Perkins¹⁰, Chiara Elena¹¹, Luca Malcovati¹¹, Anna B Fortina¹², Khalid Shoumariyeh¹³, Mohamad Jawhar¹⁴, Roberta Zanotti⁹, Patrizia Bonadonna¹⁵, Francesca Caroppo¹², Alexander Zink¹⁶, Massimo Triggiani¹⁷, Roberta Parente¹⁷, Nikolas von Bubnoff¹³, Akif S Yavuz¹⁸, Hans Hägglund¹⁹, Mattias Mattsson¹⁹, Jens Panse²⁰, Nadja Jäkel²¹, Alex Kilbertus²², Olivier Hermine²³, Michel Arock²⁴, David Fuchs²⁵, Vito Sabato²⁶, Knut Brockow¹⁶, Agnes Bretterklieber²⁷, Marek Niedoszytko⁵, Björn van Anrooij⁴, Andreas Reiter¹⁴, Jason Gotlib¹⁰, Hanneke C Kluin-Nelemans²⁸, Jiri Mayer¹, Michael Doubek¹, Peter Valent²

Affiliations

¹ Department of Hematology and Oncology, University Hospital, CEITEC Masaryk University, Brno, Czech Republic.
² Department of Internal Medicine I, Division of Hematology and Hemostaseology, Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
³ Institute of Biostatistics and Analyses, Ltd., Spinoff Company of Masaryk University, Brno, Czech Republic.
⁴ Department of Allergology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁵ Department of Allergology, Medical University of Gdańsk, Gdańsk, Poland.
⁶ Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Gdańsk, Poland.
⁷ Division of Allergy, Department of Dermatology, University of Basel, Basel, Switzerland.
⁸ Department of Dermatology, University of Cologne, Cologne, Germany.
⁹ Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.
¹⁰ Division of Hematology, Department of Medicine, Stanford University, School of Medicine/Stanford Cancer Institute, Stanford, CA, USA.
¹¹ Division of Hematology, Fondazione IRCCS Policlinico San Matteo & University of Pavia, Pavia, Italy.
¹² Pediatric Dermatology Unit, Department of Medicine, University of Padova, Padova, Italy.
¹³ Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹⁴ Hämatologie und Onkologie, III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany.
¹⁵ Allergy Unit, Verona University Hospital, Verona, Italy.
¹⁶ Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University of Munich, Munich, Germany.
¹⁷ Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
¹⁸ Division of Hematology, Istanbul Medical School, University of Istanbul, Istanbul, Turkey.
¹⁹ Department of Medical Sciences, Uppsala University, Section of Hematology, Uppsala University Hospital, Uppsala, Sweden.
²⁰ Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
²¹ Department of Internal Medicine IV, University Hospital Halle, Halle, Germany.
²² Department of Dermatology and Venereology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.
²³ Departement of Hematology, Centre National de Référence des Mastocytoses, Imagine Institute, INSERM U1123, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
²⁴ Laboratory of Hematology, Pitié-Salpêtrière Hospital, Paris, France.
²⁵ Department of Internal Medicine 3, Hematology and Oncology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.
²⁶ Faculty of Medicine and Health Sciences, Department of Immunology-Allergology-Rheumatology, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
²⁷ Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.
²⁸ Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Abstract

Background: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM.

Methods: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM.

Results: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly.

Conclusion: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.

Keywords: WHO classification; cutaneous mastocytosis; indolent systemic mastocytosis; prognostication; survival.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Marrow
Humans
Male
Mast Cells
Mastocytosis*
Mastocytosis, Systemic* / diagnosis
Mastocytosis, Systemic* / epidemiology
Prognosis
World Health Organization