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.

3 Medizinische Klinik Universitätsmedizin Mannheim Universität Heidelberg Mannheim Germany

Allergy Unit Verona University Hospital Verona Italy

Centro de Investigación del Cáncer IBMCC CIBERONC and IBSAL Departamento de Medicina and Servicio General de Citometría University of Salamanca Salamanca Spain

Department of Allergology Medical University of Gdańsk Gdańsk Poland

Department of Allergology University Medical Center Groningen University of Groningen Groningen Netherlands

Department of Dermatology and Allergy School of Medicine Technical University of Munich Munich Germany

Department of Dermatology and Venereology University Hospital Graz Graz Austria

Department of Dermatology and Venerology Kepler University Hospital Johannes Kepler University Linz Austria

Department of Dermatology Medical University of Gdańsk Gdańsk Poland

Department of Dermatology University of Cologne Cologne Germany

Department of Dermatology University of Cologne Cologne Germany; Division of Allergy Department of Dermatology and Department of Biomedicine University of Basel Basel Switzerland

Department of Hematological Biologie Pitié Salpêtrière Hospital Paris Sorbonne University Paris UMR8113 Ecole France

Department of Hematology Oncology and Stem Cell Transplantation Medical Center Faculty of Medicine University of Freiburg Freiburg Germany

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

Department of Hematology University Medical Center Groningen University of Groningen Groningen Netherlands

Department of Hematology University Medical Center Groningen University of Groningen Groningen Netherlands; Department of Allergology University Medical Center Groningen University of Groningen Groningen Netherlands

Department of Internal Medicine 1 Division of Hematology and Hemostaseology and Ludwig Boltzmann Institute for Hematology and Oncology Medical University of Vienna Vienna Austria

Department of Internal Medicine 1 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

Department of Molecular Medicine and Department of Hematology Oncology University of Pavia and Fondazione IRCCS Policlinico San Matteo Pavia Italy

Department of Oncology Haematology Haemostaseology and Stem Cell Transplantation University Hospital RWTH Aachen Aachen Germany

Division of Allergy and Clinical Immunology University of Salerno Salerno Italy

Division of Hematology Department of Medical Sciences Uppsala University Uppsala Sweden

Division of Hematology Department of Medicine Stanford University School of Medicine Stanford CA USA

Division of Hematology Istanbul Medical School University of Istanbul Istanbul Turkey

Faculty of Medicine and Health Sciences Department of Immunology Allergology Rheumatology University of Antwerp and Antwerp University Hospital Antwerp Belgium

Imagine Institute Université Paris Descartes Sorbonne Paris Cité Centre national de référence des mastocytoses Paris France

Institute of Environmental Health Medical University of Vienna Vienna Austria

Instituto de Estudios de Mastocitosis de Castilla La Mancha Hospital Virgen del Valle Toledo Spain

KU Leuven Department of Microbiology Immunology and Transplantation Allergy and Clinical Immunology Research Group and MASTeL University Hospitals Leuven Leuven Belgium

Pediatric Dermatology Unit Department of Medicine University of Padua Padua Italy

Section of Hematology Department of Medicine Verona University Hospital Verona Italy

University Clinic for Hematology and Internal Oncology Kepler University Hospital Johannes Kepler University Linz Austria

University Hospital and CEITEC Masaryk University Brno Czech Republic

University Hospital of Leipzig Leipzig Germany

Lancet Haematol. 2019 Dec;6(12):e604-e605. doi: 10.1016/S2352-3026(19)30212-1. PubMed

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