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

Wolfgang R. Sperr; Michael Kundi; Ivan Alvarez-Twose; Bjorn van Anrooij; Joanna N.G. Oude Elberink; Aleksandra Gorska; Marek Niedoszytko; Karoline V. Gleixner; Emir Hadzijusufovic; Roberta Zanotti; Patrizia Bonadonna; Massimiliano Bonifacio; Cecelia Perkins; Anja Illerhaus; Chiara Elena; Serena Merante; Khalid Shoumariyeh; Nikolas von Bubnoff; Roberta Parente; Mohamad Jawhar; Anna Belloni Fortina; Francesca Caroppo; Knut Brockow; Alexander Zink; David Fuchs; Alex J. Kilbertus; Akif Selim Yavuz; Michael Doubek; Hans Hägglund; Jens Panse; Vito Sabato; Agnes Bretterklieber; Dietger Niederwieser; Christine Breynaert; Karin Hartmann; Massimo Triggiani; Boguslaw Nedoszytko; Andreas Reiter; Alberto Orfao; Olivier Hermine; Jason Gotlib; Michel Arock; Hanneke C. Kluin-Nelemans; Peter Valent

doi:10.1016/S2352-3026(19)30166-8

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

Wolfgang R. Sperr, Michael Kundi, Ivan Alvarez-Twose, Bjorn van Anrooij, Joanna N.G. Oude Elberink, Aleksandra Gorska, Marek Niedoszytko, Karoline V. Gleixner, Emir Hadzijusufovic, Roberta Zanotti, Patrizia Bonadonna, Massimiliano Bonifacio, Cecelia Perkins, Anja Illerhaus, Chiara Elena, Serena Merante, Khalid Shoumariyeh, Nikolas von Bubnoff, Roberta Parente, Mohamad JawharAnna Belloni Fortina, Francesca Caroppo, Knut Brockow, Alexander Zink, David Fuchs, Alex J. Kilbertus, Akif Selim Yavuz, Michael Doubek, Hans Hägglund, Jens Panse, Vito Sabato, Agnes Bretterklieber, Dietger Niederwieser, Christine Breynaert, Karin Hartmann, Massimo Triggiani, Boguslaw Nedoszytko, Andreas Reiter, Alberto Orfao, Olivier Hermine, Jason Gotlib, Michel Arock, Hanneke C. Kluin-Nelemans, Peter Valent

127 Citations (Scopus)

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.

Original language	English
Journal	The Lancet Haematology
Volume	6
Issue number	12
Pages (from-to)	e638-e649
DOIs	https://doi.org/10.1016/S2352-3026(19)30166-8
Publication status	Published - 12.2019

Funding

This work was supported by the Austrian Science Fund (SFB grants F4701-B20 and F4704-B20, to PV), Deutsche Forschungsgemeinschaft (RA 2838, to AI), Koeln Fortune Program, Faculty of Medicine, University of Cologne (216/2016, to AI), Charles and Ann Johnson Foundation (to JG), and Instituto de Salud Carlos III and fondos FEDER (PI16/00642 and CB16/12/00400, to AO). VS is a senior clinical researcher of the Research Foundation Flanders/Fonds Wetenschappelijk Onderzoek (1804518N). CB is supported by the Clinical Research Fund of the University Hospitals Leuven. We thank all centres and experts in the European Competence Network on Mastocytosis (ECNM) registry group for contributing data and patients; the scientific advisors of the ECNM for their contribution to the project discussion; all technicians, study coordinators, study nurses, and colleagues for data entry into the registry system; and Susanne Herndlhofer, Nadja Jaekel, Hassiba Bouktit, Gabriele Stefanzl, Hana ?kabrahov?, Gulkan Ozkan, Tarik Tiryaki, Nicole Cabral do O, Luigi Scaffidi, Cecilia Spina, Kerstin Hamberg-Levedahl, Pietro Benvenuti, Gregor Verhoef, Peter Vandenberghe, Dominique Bullens, Marie-Anne Morren, Nele Philips, and Stephanie Pulfer for data management and data controlling. This paper is dedicated to Luis Escribano and his contributions to ECNM and the development of our ECNM registry projects. 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. This work was supported by the Austrian Science Fund (SFB grants F4701-B20 and F4704-B20 , to PV), Deutsche Forschungsgemeinschaft (RA 2838, to AI), Koeln Fortune Program, Faculty of Medicine, University of Cologne (216/2016, to AI), Charles and Ann Johnson Foundation (to JG), and Instituto de Salud Carlos III and fondos FEDER (PI16/00642 and CB16/12/00400, to AO). VS is a senior clinical researcher of the Research Foundation Flanders/Fonds Wetenschappelijk Onderzoek (1804518N). CB is supported by the Clinical Research Fund of the University Hospitals Leuven. We thank all centres and experts in the European Competence Network on Mastocytosis (ECNM) registry group for contributing data and patients; the scientific advisors of the ECNM for their contribution to the project discussion; all technicians, study coordinators, study nurses, and colleagues for data entry into the registry system; and Susanne Herndlhofer, Nadja Jaekel, Hassiba Bouktit, Gabriele Stefanzl, Hana Škabrahová, Gulkan Ozkan, Tarik Tiryaki, Nicole Cabral do O, Luigi Scaffidi, Cecilia Spina, Kerstin Hamberg-Levedahl, Pietro Benvenuti, Gregor Verhoef, Peter Vandenberghe, Dominique Bullens, Marie-Anne Morren, Nele Philips, and Stephanie Pulfer for data management and data controlling. This paper is dedicated to Luis Escribano and his contributions to ECNM and the development of our ECNM registry projects.

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10.1016/S2352-3026(19)30166-8

Cite this

Sperr, W. R., Kundi, M., Alvarez-Twose, I., van Anrooij, B., Oude Elberink, J. N. G., Gorska, A., Niedoszytko, M., Gleixner, K. V., Hadzijusufovic, E., Zanotti, R., Bonadonna, P., Bonifacio, M., Perkins, C., Illerhaus, A., Elena, C., Merante, S., Shoumariyeh, K., von Bubnoff, N., Parente, R., ... Valent, P. (2019). International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study. The Lancet Haematology, 6(12), e638-e649. https://doi.org/10.1016/S2352-3026(19)30166-8

@article{dd8f148cb93f454ea03324491bcaf9c3,

title = "International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study",

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 Espa{\~n}ola 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.",

author = "Sperr, \{Wolfgang R.\} and Michael Kundi and Ivan Alvarez-Twose and \{van Anrooij\}, Bjorn and \{Oude Elberink\}, \{Joanna N.G.\} and Aleksandra Gorska and Marek Niedoszytko and Gleixner, \{Karoline V.\} and Emir Hadzijusufovic and Roberta Zanotti and Patrizia Bonadonna and Massimiliano Bonifacio and Cecelia Perkins and Anja Illerhaus and Chiara Elena and Serena Merante and Khalid Shoumariyeh and \{von Bubnoff\}, Nikolas and Roberta Parente and Mohamad Jawhar and \{Belloni Fortina\}, Anna and Francesca Caroppo and Knut Brockow and Alexander Zink and David Fuchs and Kilbertus, \{Alex J.\} and Yavuz, \{Akif Selim\} and Michael Doubek and Hans H{\"a}gglund and Jens Panse and Vito Sabato and Agnes Bretterklieber and Dietger Niederwieser and Christine Breynaert and Karin Hartmann and Massimo Triggiani and Boguslaw Nedoszytko and Andreas Reiter and Alberto Orfao and Olivier Hermine and Jason Gotlib and Michel Arock and Kluin-Nelemans, \{Hanneke C.\} and Peter Valent",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = dec,

doi = "10.1016/S2352-3026(19)30166-8",

language = "English",

volume = "6",

pages = "e638--e649",

journal = "The Lancet Haematology",

issn = "2352-3026",

number = "12",

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Sperr, WR, Kundi, M, Alvarez-Twose, I, van Anrooij, B, Oude Elberink, JNG, Gorska, A, Niedoszytko, M, Gleixner, KV, Hadzijusufovic, E, Zanotti, R, Bonadonna, P, Bonifacio, M, Perkins, C, Illerhaus, A, Elena, C, Merante, S, Shoumariyeh, K, von Bubnoff, N, Parente, R, Jawhar, M, Belloni Fortina, A, Caroppo, F, Brockow, K, Zink, A, Fuchs, D, Kilbertus, AJ, Yavuz, AS, Doubek, M, Hägglund, H, Panse, J, Sabato, V, Bretterklieber, A, Niederwieser, D, Breynaert, C, Hartmann, K, Triggiani, M, Nedoszytko, B, Reiter, A, Orfao, A, Hermine, O, Gotlib, J, Arock, M, Kluin-Nelemans, HC & Valent, P 2019, 'International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study', The Lancet Haematology, vol. 6, no. 12, pp. e638-e649. https://doi.org/10.1016/S2352-3026(19)30166-8

TY - JOUR

T1 - International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study

AU - Sperr, Wolfgang R.

AU - Kundi, Michael

AU - Alvarez-Twose, Ivan

AU - van Anrooij, Bjorn

AU - Oude Elberink, Joanna N.G.

AU - Gorska, Aleksandra

AU - Niedoszytko, Marek

AU - Gleixner, Karoline V.

AU - Hadzijusufovic, Emir

AU - Zanotti, Roberta

AU - Bonadonna, Patrizia

AU - Bonifacio, Massimiliano

AU - Perkins, Cecelia

AU - Illerhaus, Anja

AU - Elena, Chiara

AU - Merante, Serena

AU - Shoumariyeh, Khalid

AU - von Bubnoff, Nikolas

AU - Parente, Roberta

AU - Jawhar, Mohamad

AU - Belloni Fortina, Anna

AU - Caroppo, Francesca

AU - Brockow, Knut

AU - Zink, Alexander

AU - Fuchs, David

AU - Kilbertus, Alex J.

AU - Yavuz, Akif Selim

AU - Doubek, Michael

AU - Hägglund, Hans

AU - Panse, Jens

AU - Sabato, Vito

AU - Bretterklieber, Agnes

AU - Niederwieser, Dietger

AU - Breynaert, Christine

AU - Hartmann, Karin

AU - Triggiani, Massimo

AU - Nedoszytko, Boguslaw

AU - Reiter, Andreas

AU - Orfao, Alberto

AU - Hermine, Olivier

AU - Gotlib, Jason

AU - Arock, Michel

AU - Kluin-Nelemans, Hanneke C.

AU - Valent, Peter

PY - 2019/12

Y1 - 2019/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85075358050

U2 - 10.1016/S2352-3026(19)30166-8

DO - 10.1016/S2352-3026(19)30166-8

M3 - Journal articles

C2 - 31676322

AN - SCOPUS:85075358050

SN - 2352-3026

VL - 6

SP - e638-e649

JO - The Lancet Haematology

JF - The Lancet Haematology

IS - 12

ER -

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

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