. 2019 Dec;6(12):e638-e649.

doi: 10.1016/S2352-3026(19)30166-8. Epub 2019 Oct 31.

International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study

Wolfgang R Sperr¹, Michael Kundi², Ivan Alvarez-Twose³, Bjorn van Anrooij⁴, Joanna N G Oude Elberink⁵, Aleksandra Gorska⁶, Marek Niedoszytko⁶, Karoline V Gleixner⁷, Emir Hadzijusufovic⁸, Roberta Zanotti⁹, Patrizia Bonadonna¹⁰, Massimiliano Bonifacio⁹, Cecelia Perkins¹¹, Anja Illerhaus¹², Chiara Elena¹³, Serena Merante¹³, Khalid Shoumariyeh¹⁴, Nikolas von Bubnoff¹⁵, Roberta Parente¹⁶, Mohamad Jawhar¹⁷, Anna Belloni Fortina¹⁸, Francesca Caroppo¹⁸, Knut Brockow¹⁹, Alexander Zink¹⁹, David Fuchs²⁰, Alex J Kilbertus²¹, Akif Selim Yavuz²², Michael Doubek²³, Hans Hägglund²⁴, Jens Panse²⁵, Vito Sabato²⁶, Agnes Bretterklieber²⁷, Dietger Niederwieser²⁸, Christine Breynaert²⁹, Karin Hartmann³⁰, Massimo Triggiani¹⁶, Boguslaw Nedoszytko³¹, Andreas Reiter¹⁷, Alberto Orfao³², Olivier Hermine³³, Jason Gotlib¹¹, Michel Arock³⁴, Hanneke C Kluin-Nelemans³⁵, Peter Valent⁷

Affiliations

¹ Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria. Electronic address: wolfgang.r.sperr@meduniwien.ac.at.
² Institute of Environmental Health, Medical University of Vienna, Vienna, Austria.
³ Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain.
⁴ Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Allergology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁵ Department of Allergology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁶ Department of Allergology, Medical University of Gdańsk, Gdańsk, Poland.
⁷ Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
⁸ Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria; Internal Medicine Small Animals, University Clinic for Small Animals, Department/University Clinic for Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria.
⁹ Section of Hematology, Department of Medicine, Verona University Hospital, Verona, Italy.
¹⁰ Allergy Unit, Verona University Hospital, Verona, Italy.
¹¹ Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
¹² Department of Dermatology, University of Cologne, Cologne, Germany.
¹³ Department of Molecular Medicine and Department of Hematology Oncology, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
¹⁴ Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹⁵ Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Hematology and Oncology, Medical Center, University of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
¹⁶ Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
¹⁷ III Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany.
¹⁸ Pediatric Dermatology Unit, Department of Medicine, University of Padua, Padua, Italy.
¹⁹ Department of Dermatology and Allergy, School of Medicine, Technical University of Munich, Munich, Germany.
²⁰ University Clinic for Hematology and Internal Oncology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.
²¹ Department of Dermatology and Venerology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.
²² Division of Hematology, Istanbul Medical School, University of Istanbul, Istanbul, Turkey.
²³ University Hospital and CEITEC Masaryk University, Brno, Czech Republic.
²⁴ Division of Hematology, Department of Medical Sciences Uppsala University, Uppsala, Sweden.
²⁵ Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
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, University Hospital Graz, Graz, Austria.
²⁸ University Hospital of Leipzig, Leipzig, Germany.
²⁹ KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group and MASTeL, University Hospitals Leuven, Leuven, Belgium.
³⁰ Department of Dermatology, University of Cologne, Cologne, Germany; Division of Allergy, Department of Dermatology, and Department of Biomedicine, University of Basel, Basel, Switzerland.
³¹ Department of Dermatology, Medical University of Gdańsk, Gdańsk, Poland.
³² Centro de Investigación del Cáncer/IBMCC (USAL/CSIC), CIBERONC and IBSAL, Departamento de Medicina and Servicio General de Citometría, University of Salamanca, Salamanca, Spain.
³³ Imagine Institute Université Paris Descartes, Sorbonne, Paris Cité, Centre national de référence des mastocytoses, Paris, France.
³⁴ Department of Hematological Biologie, Pitié-Salpêtrière Hospital, Paris Sorbonne University, Paris UMR8113, Ecole, France.
³⁵ Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

PMID: 31676322
PMCID: PMC7115823
DOI: 10.1016/S2352-3026(19)30166-8

International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study

Wolfgang R Sperr et al. Lancet Haematol. 2019 Dec.

. 2019 Dec;6(12):e638-e649.

doi: 10.1016/S2352-3026(19)30166-8. Epub 2019 Oct 31.

Authors

Affiliations

¹ Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria. Electronic address: wolfgang.r.sperr@meduniwien.ac.at.
² Institute of Environmental Health, Medical University of Vienna, Vienna, Austria.
³ Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain.
⁴ Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Allergology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁵ Department of Allergology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁶ Department of Allergology, Medical University of Gdańsk, Gdańsk, Poland.
⁷ Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
⁸ Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria; Internal Medicine Small Animals, University Clinic for Small Animals, Department/University Clinic for Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria.
⁹ Section of Hematology, Department of Medicine, Verona University Hospital, Verona, Italy.
¹⁰ Allergy Unit, Verona University Hospital, Verona, Italy.
¹¹ Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
¹² Department of Dermatology, University of Cologne, Cologne, Germany.
¹³ Department of Molecular Medicine and Department of Hematology Oncology, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
¹⁴ Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹⁵ Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Hematology and Oncology, Medical Center, University of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
¹⁶ Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
¹⁷ III Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany.
¹⁸ Pediatric Dermatology Unit, Department of Medicine, University of Padua, Padua, Italy.
¹⁹ Department of Dermatology and Allergy, School of Medicine, Technical University of Munich, Munich, Germany.
²⁰ University Clinic for Hematology and Internal Oncology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.
²¹ Department of Dermatology and Venerology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.
²² Division of Hematology, Istanbul Medical School, University of Istanbul, Istanbul, Turkey.
²³ University Hospital and CEITEC Masaryk University, Brno, Czech Republic.
²⁴ Division of Hematology, Department of Medical Sciences Uppsala University, Uppsala, Sweden.
²⁵ Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
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, University Hospital Graz, Graz, Austria.
²⁸ University Hospital of Leipzig, Leipzig, Germany.
²⁹ KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group and MASTeL, University Hospitals Leuven, Leuven, Belgium.
³⁰ Department of Dermatology, University of Cologne, Cologne, Germany; Division of Allergy, Department of Dermatology, and Department of Biomedicine, University of Basel, Basel, Switzerland.
³¹ Department of Dermatology, Medical University of Gdańsk, Gdańsk, Poland.
³² Centro de Investigación del Cáncer/IBMCC (USAL/CSIC), CIBERONC and IBSAL, Departamento de Medicina and Servicio General de Citometría, University of Salamanca, Salamanca, Spain.
³³ Imagine Institute Université Paris Descartes, Sorbonne, Paris Cité, Centre national de référence des mastocytoses, Paris, France.
³⁴ Department of Hematological Biologie, Pitié-Salpêtrière Hospital, Paris Sorbonne University, Paris UMR8113, Ecole, France.
³⁵ Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

PMID: 31676322
PMCID: PMC7115823
DOI: 10.1016/S2352-3026(19)30166-8

Abstract

Background: The WHO classification separates mastocytosis into distinct variants, but prognostication remains a clinical challenge. The aim of this study was to improve prognostication for patients with mastocytosis.

Methods: We analysed data of the registry of the European Competence Network on Mastocytosis including 1639 patients (age 17-90 years) diagnosed with mastocytosis according to WHO criteria between Jan 12, 1978, and March 16, 2017. Univariate and multivariate analyses with Cox regression were applied to identify prognostic variables predicting survival outcomes and to establish a prognostic score. We validated this International Prognostic Scoring System in Mastocytosis (IPSM) with data of 462 patients (age 17-79 years) from the Spanish network Red Española de Mastocitosis diagnosed between Jan 22, 1998, and Nov 2, 2017.

Findings: The prognostic value of the WHO classification was confirmed in our study (p<0·0001). For patients with non-advanced mastocytosis (n=1380), we identified age 60 years or older (HR 10·75, 95% CI 5·68-20·32) and a concentration of alkaline phosphatase 100 U/L or higher (2·91, 1·60-5·30) as additional independent prognostic variables for overall survival. The resulting scoring system divided patients with non-advanced mastocytosis into three groups: low (no risk factors), intermediate 1 (one risk factor), and intermediate 2 (two risk factors). Overall survival and progression-free survival differed significantly among these groups (p<0·0001). In patients with advanced mastocytosis (n=259), age 60 years or older (HR 2·14, 95% CI 1·42-3·22), a concentration of tryptase 125 ng/mL or higher (1·81, 1·20-2·75), a leukocyte count of 16 × 10⁹ per L or higher (1·88, 1·27-2·79), haemoglobin of 11 g/dL or lower (1·71, 1·13-2·57), a platelet count of 100 × 10⁹ per L or lower (1·63, 1·13-2·34), and skin involvement (0·46, 0·30-0·69) were prognostic variables. Based on these variables, a separate score for advanced mastocytosis with four risk categories was established, with significantly different outcomes for overall survival and progression-free survival (p<0·0001). The prognostic value of both scores was confirmed in 413 patients with non-advanced disease and 49 with advanced mastocytosis from the validation cohort.

Interpretation: The IPSM scores for patients with non-advanced and advanced mastocytosis can be used to predict survival outcomes and guide treatment decisions. However, the predictive value of the IPSM needs to be confirmed in forthcoming trials.

Funding: Austrian Science Fund, Deutsche Forschungsgemeinschaft, Koeln Fortune Program, Charles and Ann Johnson Foundation, Instituto de Salud Carlos III, Fondos FEDER, Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek, Clinical Research-Fund of the University Hospitals Leuven, and Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek.

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Conflict of interest statement

Declaration of interests

WRS declares honoraria from AbbVie, Amgen, Celgene, Daiichi Sankyo, Deciphera, Incyte, Jazz, Novartis, Pfizer, and Thermo Fisher; and travel grants from Pfizer and Roche. BvA, IA-T, and ASY declare honoraria from Novartis. KVG declares honoraria from Pfizer, Novartis, Roche, BMS, Sanofi, and Incyte; and travel grants from Roche and AbbVie. RZ declares honoraria from Deciphera, Novartis, and Takeda. MB declares honoraria from Pfizer, Amgen, and Incyte; and research funding from Novartis. CE declares honoraria from Novartis and Pfizer. KS declares honoraria from Novartis; and travel grants from AbbVie. NvB declares honoraria from AstraZeneca, Amgen, Novartis, and BMS; and research funding from Novartis. AZ declares honoraria from or has participated in trials for AbbVie, Almirall, Beiersdorf Dermo Medical, Bencard Allergie, BMS, Celgene, Eli Lilly, GSK, Janssen-Cilag, Miltenyi Biotec, Novartis, Sanofi-Aventis, and Takeda Pharma. DF declares honoraria from Novartis, Pfizer, and Roche; and travel grants from Roche. JP declares honoraria from Exion, BMS, Boehringer Ingelheim, Grünenthal, MSD, Novartis, Pfizer, Chugai, and Roche. DN declares research funding from Novartis; and non-financial support from Amgen and Cellectis. CB declares honoraria from Thermo Fisher Phadia; and travel grants from Shire/Takeda, HAL, and ALK. KH declares honoraria from ALK, Blueprint, Deciphera, and Novartis; and research funding from Euroimmun. MT declares honoraria from Blueprint, Deciphera, and Novartis. AR declares honoraria from Blueprint, Deciphera, Incyte, and Novartis. AO declares honoraria from Becton Dickinson, Janssen, and Novartis; research funding from Becton Dickinson, Cytognos, and Immunostep; and is an inventor on patents licensed to Cytognos, Immunostep, Fagotrace, and Becton-Dickinson that return royalties to the University of Salamanca and EuroFlow. OH declares honoraria from ABscience; and research funding from Alexion, Celgene, and Novartis. JG declares honoraria and research funding from Blueprint, Deciphera, and Novartis. MA declares honoraria from Deciphera, Allakos, and Blueprint; and research funding from Allakos and Blueprint. HCK-N declares research funding from Novartis. PV declares honoraria from Blueprint, Celgene, Deciphera, Incyte, Novartis, and Pfizer; and research funding from Pfizer, Incyte, and Celgene. MK, JNGOE, AG, MN, EH, PB, CP, AI, SM, RP, MJ, ABF, FC, KB, AJK, MD, HH, VS, AB, and BN declare no competing interests.

Figures

**Figure 1. Study profile**
Patients were selected from the ECNM registry (A) and REMA (B). In the ECNM cohort, only patients with at least 2 days of follow-up were included. All patients were included in analyses of overall survival and event-free survival. ECNM=European Competence Network on Mastocytosis. REMA=Red Española de Mastocitosis. *Included in analyses of progression-free survival. †Children (aged <17 years) were excluded from the assessment of prognostic factors and development of the score because, for most children, no bone marrow studies were available and because the disease is different. Patients with mast cell sarcoma were excluded because of the rarity of the disease and its unique pathology and pathogenesis. ‡Those excluded were children (aged <17 years), had cutaneous mastocytosis without a bone marrow study, had less than 12 months of follow-up for non-advanced systemic mastocytosis, or did not have enough data.

**Figure 2. Survival outcomes in WHO subgroups of mastocytosis**
Kaplan–Meier curves show the probability of overall survival (A) and progression-free survival (B) in subgroups of patients with mastocytosis, defined by WHO criteria.

**Figure 3. Survival outcomes according to the IPSM score in patients with non-advanced and advanced systemic mastocytosis**
Kaplan–Meier curves show the probability of overall survival (A, C) and progression-free survival (B, D) in patients with non-advanced and advanced systemic mastocytosis, defined by the IPSM. Upper panels (A, B) show that patients with non-advanced systemic mastocytosis at low risk (no risk factors [low]) and intermediate risk (one [int-1] or two [int-2] additional risk factors) differed significantly and had a favourable outcome compared with patients with advanced systemic mastocytosis (AdvSM). Lower panels (C, D) show that patients with advanced systemic mastocytosis and no additional risk factors (AdvSM-1) differed significantly from those with one (AdvSM-2), two to three (AdvSM-3), or four to five (AdvSM-4) risk factors. IPSM=international prognostic scoring system for mastocytosis.

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Comment in

A useful add-on international prognostic score for mastocytosis?
Barete S. Barete S. Lancet Haematol. 2019 Dec;6(12):e604-e605. doi: 10.1016/S2352-3026(19)30212-1. Epub 2019 Oct 31. Lancet Haematol. 2019. PMID: 31676323 No abstract available.

References

1. Cohen SS, Skovbo S, Vestergaard H, et al. Epidemiology of systemic mastocytosis in Denmark. Br J Haematol. 2014;166:521–28. - PubMed
1. Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129:1420–27. - PMC - PubMed
1. Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001;25:603–25. - PubMed
1. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113:5727–36. - PubMed
1. Valent P, Akin C, Escribano L, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007;37:435–53. - PubMed

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International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study

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International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study

Authors

Affiliations

Abstract

Conflict of interest statement

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