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. 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.
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.
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.
Authors: M Jawhar; J Schwaab; S Schnittger; M Meggendorfer; M Pfirrmann; K Sotlar; H-P Horny; G Metzgeroth; S Kluger; N Naumann; C Haferlach; T Haferlach; P Valent; W-K Hofmann; A Fabarius; N C P Cross; A Reiter Journal: Leukemia Date: 2015-10-14 Impact factor: 11.528
Authors: David P Steensma; Rafael Bejar; Siddhartha Jaiswal; R Coleman Lindsley; Mikkael A Sekeres; Robert P Hasserjian; Benjamin L Ebert Journal: Blood Date: 2015-04-30 Impact factor: 22.113
Authors: M Jawhar; J Schwaab; D Hausmann; J Clemens; N Naumann; T Henzler; H-P Horny; K Sotlar; S O Schoenberg; N C P Cross; A Fabarius; W-K Hofmann; P Valent; G Metzgeroth; A Reiter Journal: Leukemia Date: 2016-07-15 Impact factor: 11.528
Authors: Peter Valent; Joanna N G Oude Elberink; Aleksandra Gorska; Magdalena Lange; Roberta Zanotti; Björn van Anrooij; Massimiliano Bonifacio; Patrizia Bonadonna; Karoline V Gleixner; Emir Hadzijusufovic; Cecelia Perkins; Karin Hartmann; Anja Illerhaus; Serena Merante; Chiara Elena; Khalid Shoumariyeh; Nikolas von Bubnoff; Roberta Parente; Massimo Triggiani; Juliana Schwaab; Mohamad Jawhar; Francesca Caroppo; Anna Belloni Fortina; Knut Brockow; Rosemarie Greul; Akif Selim Yavuz; Michael Doubek; Mattias Mattsson; Hans Hagglund; Jens Panse; Vito Sabato; Elisabeth Aberer; Haifa Kathrin Al-Ali; Marie-Anne Morren; Judit Varkonyi; Alexander Zink; Marek Niedoszytko; Dietger Niederwieser; Luca Malcovati; Andreas Reiter; Vanessa Kennedy; Jason Gotlib; Olivier Lortholary; Olivier Hermine; Michel Arock; Hanneke Kluin-Nelemans; Wolfgang R Sperr Journal: J Allergy Clin Immunol Pract Date: 2018-11-08
Authors: P Valent; H P Horny; L Escribano; B J Longley; C Y Li; L B Schwartz; G Marone; R Nuñez; C Akin; K Sotlar; W R Sperr; K Wolff; R D Brunning; R M Parwaresch; K F Austen; K Lennert; D D Metcalfe; J W Vardiman; J M Bennett Journal: Leuk Res Date: 2001-07 Impact factor: 3.156
Authors: G Hoermann; K V Gleixner; G E Dinu; M Kundi; G Greiner; F Wimazal; E Hadzijusufovic; G Mitterbauer; C Mannhalter; P Valent; W R Sperr Journal: Allergy Date: 2014-04-17 Impact factor: 13.146
Authors: P Valent; C Akin; L Escribano; M Födinger; K Hartmann; K Brockow; M Castells; W R Sperr; H C Kluin-Nelemans; N A T Hamdy; O Lortholary; J Robyn; J van Doormaal; K Sotlar; A W Hauswirth; M Arock; O Hermine; A Hellmann; M Triggiani; M Niedoszytko; L B Schwartz; A Orfao; H-P Horny; D D Metcalfe Journal: Eur J Clin Invest Date: 2007-06 Impact factor: 4.686
Authors: Javier I Muñoz-González; María Jara-Acevedo; Iván Alvarez-Twose; Jason D Merker; Cristina Teodosio; Yanli Hou; Ana Henriques; Krishna M Roskin; Laura Sanchez-Muñoz; Albert G Tsai; Carolina Caldas; Almudena Matito; J Ignacio Sánchez-Gallego; Andrea Mayado; Noelia Dasilva-Freire; Jason R Gotlib; Luis Escribano; Alberto Orfao; Andrés C García-Montero Journal: Blood Adv Date: 2018-11-13
Authors: Mohamad Jawhar; Juliana Schwaab; Nicole Naumann; Hans-Peter Horny; Karl Sotlar; Torsten Haferlach; Georgia Metzgeroth; Alice Fabarius; Peter Valent; Wolf-Karsten Hofmann; Nicholas C P Cross; Manja Meggendorfer; Andreas Reiter Journal: Blood Date: 2017-04-19 Impact factor: 25.476
Authors: Gabriella Galatà; Andrés C García-Montero; Thomas Kristensen; Ahmed A Z Dawoud; Javier I Muñoz-González; Manja Meggendorfer; Paola Guglielmelli; Yvette Hoade; Ivan Alvarez-Twose; Christian Gieger; Konstantin Strauch; Luigi Ferrucci; Toshiko Tanaka; Stefania Bandinelli; Theresia M Schnurr; Torsten Haferlach; Sigurd Broesby-Olsen; Hanne Vestergaard; Michael Boe Møller; Carsten Bindslev-Jensen; Alessandro M Vannucchi; Alberto Orfao; Deepti Radia; Andreas Reiter; Andrew J Chase; Nicholas C P Cross; William J Tapper Journal: Am J Hum Genet Date: 2021-01-08 Impact factor: 11.025
Authors: Oscar González-López; Javier I Muñoz-González; Alberto Orfao; Iván Álvarez-Twose; Andrés C García-Montero Journal: Cancers (Basel) Date: 2022-05-18 Impact factor: 6.575
Authors: Mathias Schneeweiss-Gleixner; Yüksel Filik; Gabriele Stefanzl; Daniela Berger; Irina Sadovnik; Karin Bauer; Dubravka Smiljkovic; Gregor Eisenwort; Nadine Witzeneder; Georg Greiner; Gregor Hoermann; Ana-Iris Schiefer; Juliana Schwaab; Mohamad Jawhar; Andreas Reiter; Wolfgang R Sperr; Michel Arock; Peter Valent; Karoline V Gleixner Journal: Cancers (Basel) Date: 2022-06-23 Impact factor: 6.575
Authors: Michel Arock; Karl Sotlar; Jason Gotlib; Wolfgang R Sperr; Karin Hartmann; Lawrence B Schwartz; Cem Akin; Hans-Peter Horny; Peter Valent Journal: Leuk Lymphoma Date: 2019-12-26
Authors: Jason Gotlib; Tracy I George; Melody C Carter; K Frank Austen; Bruce Bochner; Daniel F Dwyer; Jonathan J Lyons; Matthew J Hamilton; Joseph Butterfield; Patrizia Bonadonna; Catherine Weiler; Stephen J Galli; Lawrence B Schwartz; Hanneke Oude Elberink; Anne Maitland; Theoharis Theoharides; Celalettin Ustun; Hans-Peter Horny; Alberto Orfao; Michael Deininger; Deepti Radia; Mohamad Jawhar; Hanneke Kluin-Nelemans; Dean D Metcalfe; Michel Arock; Wolfgang R Sperr; Peter Valent; Mariana Castells; Cem Akin Journal: J Allergy Clin Immunol Date: 2021-03-11 Impact factor: 14.290
Authors: Georg Greiner; Bettina Sprinzl; Aleksandra Górska; Franz Ratzinger; Michael Gurbisz; Nadine Witzeneder; Klaus G Schmetterer; Bettina Gisslinger; Goekhan Uyanik; Emir Hadzijusufovic; Harald Esterbauer; Karoline V Gleixner; Maria T Krauth; Michael Pfeilstöcker; Felix Keil; Heinz Gisslinger; Boguslaw Nedoszytko; Marek Niedoszytko; Wolfgang R Sperr; Peter Valent; Gregor Hoermann Journal: Blood Date: 2021-01-14 Impact factor: 22.113