ESTABLISHMENT OF A SIMPLE RISK SCORE TO PREDICT SYSTEMIC MASTOCYTOSIS (SM) IN ADULT PATIENTS WITH MASTOCYTOSIS IN THE SKIN (MIS)
Author(s): ,
David Fuchs
Affiliations:
Department of Internal Medicine 3 - Hematology and Oncology,Kepler University Hospital, Johannes Kepler University,Linz,Austria
,
Alex Kilbertus
Affiliations:
Department of Dermatology and Allergology,Kepler University Hospital, Johannes Kepler University,Linz,Austria
,
Philipp Hockl
Affiliations:
Department of Internal Medicine 3 - Hematology and Oncology,Kepler University Hospital, Johannes Kepler University,Linz,Austria
,
Nikolas von Bubnoff
Affiliations:
Department of Hematology, Oncology and Stem Cell Transplantation,Medical Center, Faculty of Medicine, Freiburg,Freiburg,Germany;German Cancer Consortium (DKTK), partner site Freiburg,Freiburg,Germany;German Cancer Research Center (DKFZ),Heidelberg,Germany
,
Khalid Shoumariyeh
Affiliations:
Department of Hematology, Oncology and Stem Cell Transplantation,Medical Center, Faculty of Medicine, Freiburg,Freiburg,Germany;German Cancer Consortium (DKTK), partner site Freiburg,Freiburg,Germany;German Cancer Research Center (DKFZ),Heidelberg,Germany
,
Roberta Zanotti
Affiliations:
Section of Hematology, Department of Medicine,Verona University Hospital,Verona,Italy
,
Patrizia Bonadonna
Affiliations:
Allergy Unit,Verona University Hospital,Verona,Italy
,
Luigi Scaffidi
Affiliations:
Section of Hematology, Department of Medicine,Verona University Hospital,Verona,Italy
,
Michael Doubek
Affiliations:
University Hospital Brno,Brno,Czech Republic
,
Hanneke Oude Elderink
Affiliations:
Department of Hematology,University Medical Center Groningen, University of Groningen,Groningen,Netherlands
,
Lambert F.R. Span
Affiliations:
Department of Hematology,University Medical Center Groningen, University of Groningen,Groningen,Netherlands
,
Olivier Hermine
Affiliations:
Service Hèmatologie Adulte,Hôpital Necker-Enfants malades,Paris,France
,
Chiara Elena
Affiliations:
Department of Hematology Oncology,IRCCS Policlinico San Matteo Foundation ,Pavia,Italy
,
Pietro Benvenuti
Affiliations:
Department of Hematology Oncology , School of Hematology,University of Pavia and IRCCS Policlinico San Matteo Foundation,Pavia,Italy
,
Akif Selim Yavuz
Affiliations:
Division of Hematology, Department of Internal Medicine,University of Istanbul,Istanbul,Turkey
,
Knut Brockow
Affiliations:
Department of Dermatology and Allergy Biederstein,Technische Universität München,Munich,Germany
,
Alexander Zink
Affiliations:
Department of Dermatology and Allergy Biederstein,Technische Universität München,Munich,Germany
,
Elisabeth Aberer
Affiliations:
Department of Dermatology and Venereology,Medical University of Graz,Graz,Austria
,
Aleksandra Gorska
Affiliations:
Department of Allergology,Medical University of Gdańsk,Gdańsk,Poland
,
Jan Romantowski
Affiliations:
Department of Allergology,Medical University of Gdańsk,Gdańsk,Poland
,
Emir Hadzijusufovic
Affiliations:
Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Cluster Oncology,Medical University of Vienna,Vienna,Austria
,
Anna Belloni Fortina
Affiliations:
Pediatric Dermatology Unit, Department of Medicine,University of Padua,Padua,Italy
,
Francesca Caroppo
Affiliations:
Pediatric Dermatology Unit, Department of Medicine,University of Padua,Padua,Italy
,
Cecelia Perkins
Affiliations:
Stanford Cancer Institute/Stanford University School of Medicine,Stanford, CA,United States
,
Anja Illerhaus
Affiliations:
Department of Dermatology,University of Cologne,Cologne,Germany
,
Jens Panse
Affiliations:
Department of Oncology, Hematology, Hemostaseology and Stem Cell Transplantation,Medical Faculty, University Hospital RWTH Aachen,Aachen,Germany
,
Vladan Vucinic
Affiliations:
University Hospital of Leipzig,Leipzig,Germany
,
Mohamad Jawhar
Affiliations:
III. Medizinische Klinik,Universitätsmedizin Mannheim, Universität Heidelberg,Mannheim,Germany
,
Vito Sabato
Affiliations:
Faculty of Medicine and Health Sciences, Department of Immunology-Allergology-Rheumatology,University of Antwerp and Antwerp University Hospital,Antwerpen,Belgium
,
Massimo Triggiani
Affiliations:
Division of Allergy and Clinical Immunology, Department of Medicine,University of Salerno,Salerno,Italy
,
Roberta Parente
Affiliations:
Division of Allergy and Clinical Immunology, Department of Medicine,University of Salerno,Salerno,Italy
,
Hans Hagglund
Affiliations:
Cancer Center,Uppsala University Hospital,Uppsala,Sweden
,
Christine Breynaert
Affiliations:
University Hospitals Leuven and KU Leuven,Leuven,Belgium
,
Jason Gotlib
Affiliations:
Stanford Cancer Institute/Stanford University School of Medicine,Stanford, CA,United States
,
Andreas Reiter
Affiliations:
III. Medizinische Klinik,Universitätsmedizin Mannheim, Universität Heidelberg,Mannheim,Germany
,
Karin Hartmann
Affiliations:
Department of Dermatology,University of Cologne,Cologne,Germany;Department of Dermatology,University of Luebeck,Luebeck,Germany
,
Marek Niedoszytko
Affiliations:
Department of Allergology,Medical University of Gdańsk,Gdańsk,Poland
,
Hanneke Kluin Nelemans
Affiliations:
Department of Hematology,University Medical Center Groningen, University of Groningen,Groningen,Netherlands
,
Wolfgang R. Sperr
Affiliations:
Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Cluster Oncology,Medical University of Vienna,Vienna,Austria
,
Peter Valent
Affiliations:
Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Cluster Oncology,Medical University of Vienna,Vienna,Austria
Rosemarie Greul
Affiliations:
Department of Internal Medicine 3 - Hematology and Oncology,Kepler University Hospital, Johannes Kepler University,Linz,Austria
EHA Library. Fuchs D. 06/16/18; 214527; S813
David Fuchs
David Fuchs
Contributions
Abstract

Abstract: S813

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 12:30 - 12:45

Location: Room A2

Background
Mastocytosis is a clonal mast cell disease which, in adults, most commonly affects skin, bone marrow and other organs. Symptoms and serum tryptase levels vary, and there are patients with pure cutaneous mastocytosis (CM). It is generally appreciated that all adult patients with MIS require a bone marrow biopsy (BMB) in order to confirm the presence of SM. Although BMB is safe, it may be painful and cause complications. Existing risk scores are based on relatively few patients and a limited set of parameters.

Aims
We aimed at creating a simple and solid risk score to predict SM in adult patients with MIS. We hypothesized that there are patients at low risk of SM which may be relevant in clinical practice.

Methods
The European Competence Network on Mastocytosis (ECNM) registry is the largest collection of data on patients with mastocytosis. 1145 patients of at least 18 years with MIS who had a BMB within six months of diagnosis were included. Patients with advanced mastocytosis (ASM, MCL, SM-AHN) were excluded. We identified significant variables in univariate analysis and created a multivariate regression model using the whole population as a training and validation set (bootstrapping). A risk score was derived and the model and score were validated with receiver operating curve (ROC) area under the curve (AUC).

Results
Of 1145 patients, 944 had SM and 201 had CM. Among these 1145 patients, 63.7% were female, with a median age of 44±13.3 years (18-81 years) and good performance status (ECOG 0-1, 97.6%). They were highly symptomatic (skin symptoms, 81.4%; other, 65.5%). Almost all patients had typical skin lesions (>97%) and tryptase levels varied greatly (median 29.3±81.9 ng/ml, range: 1-885). In a univariate analysis to determine predictors of SM in patients with MIS, significant variables were typical MIS (p=0.001), a positive Darier’s sign (p=0.020), constitutional/cardiovascular symptoms (p=0.002), bone symptoms/osteoporosis (p<0.001), gastrointestinal symptoms (p=0.004), serum tryptase (p<0.001), palpable spleen (p=0.003), age >65 years (p=0.009), lactate dehydrogenase (p=0.003), monocytes (p=0.001) and beta2-microglobulin (p=0.047). In the multivariate regression model, tryptase level (p<0.001), constitutional/cardiovascular symptoms (p=0.014) and bone symptoms/osteoporosis (p<0.001) were identified as independent predictors of SM (p<0.001, Nagelkerke R2=0.462, Hosmer-Lemeshow p=0.177). The model correctly classified 88.1% of the cases as SM (sensitivity 90.7%, specifity 69.1%, positive predictive value 95.5%, negative predictive value 50.3%). A risk score was derived and points were assigned to all variables, creating a six-point scale with a risk of SM ranging from 10.7% to 98.0% (Fig. 1). ROC AUC was 0.871 for the model and 0.867 for the risk score. Bootstrap validation (k=1000) led to an optimism-corrected AUC of 0.853 for the model and 0.849 for the score. Of all MIS patients, 17.4% (n=199) were at low risk (-1 and 0 points, 10.7 and 24.7% risk of SM), 14.5% (n=166) at medium risk (1 and 2 points, 47.1 and 70.7%) and 68.1% (n=779) at high risk (3-5 points, 86.8-98%).

Conclusion
Using a large data set of the ECNM registry, we created a risk score to better predict SM in patients with MIS. Although it will need validation in independent cohorts, our score seems to be valid and may discriminate between patients with SM and CM. Our new score may thus have clinical implications and may assist in the decision to recommend a BMB in adults with MIS.  

 

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Mast cell disease, Mastocytosis, Risk factor

Abstract: S813

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 12:30 - 12:45

Location: Room A2

Background
Mastocytosis is a clonal mast cell disease which, in adults, most commonly affects skin, bone marrow and other organs. Symptoms and serum tryptase levels vary, and there are patients with pure cutaneous mastocytosis (CM). It is generally appreciated that all adult patients with MIS require a bone marrow biopsy (BMB) in order to confirm the presence of SM. Although BMB is safe, it may be painful and cause complications. Existing risk scores are based on relatively few patients and a limited set of parameters.

Aims
We aimed at creating a simple and solid risk score to predict SM in adult patients with MIS. We hypothesized that there are patients at low risk of SM which may be relevant in clinical practice.

Methods
The European Competence Network on Mastocytosis (ECNM) registry is the largest collection of data on patients with mastocytosis. 1145 patients of at least 18 years with MIS who had a BMB within six months of diagnosis were included. Patients with advanced mastocytosis (ASM, MCL, SM-AHN) were excluded. We identified significant variables in univariate analysis and created a multivariate regression model using the whole population as a training and validation set (bootstrapping). A risk score was derived and the model and score were validated with receiver operating curve (ROC) area under the curve (AUC).

Results
Of 1145 patients, 944 had SM and 201 had CM. Among these 1145 patients, 63.7% were female, with a median age of 44±13.3 years (18-81 years) and good performance status (ECOG 0-1, 97.6%). They were highly symptomatic (skin symptoms, 81.4%; other, 65.5%). Almost all patients had typical skin lesions (>97%) and tryptase levels varied greatly (median 29.3±81.9 ng/ml, range: 1-885). In a univariate analysis to determine predictors of SM in patients with MIS, significant variables were typical MIS (p=0.001), a positive Darier’s sign (p=0.020), constitutional/cardiovascular symptoms (p=0.002), bone symptoms/osteoporosis (p<0.001), gastrointestinal symptoms (p=0.004), serum tryptase (p<0.001), palpable spleen (p=0.003), age >65 years (p=0.009), lactate dehydrogenase (p=0.003), monocytes (p=0.001) and beta2-microglobulin (p=0.047). In the multivariate regression model, tryptase level (p<0.001), constitutional/cardiovascular symptoms (p=0.014) and bone symptoms/osteoporosis (p<0.001) were identified as independent predictors of SM (p<0.001, Nagelkerke R2=0.462, Hosmer-Lemeshow p=0.177). The model correctly classified 88.1% of the cases as SM (sensitivity 90.7%, specifity 69.1%, positive predictive value 95.5%, negative predictive value 50.3%). A risk score was derived and points were assigned to all variables, creating a six-point scale with a risk of SM ranging from 10.7% to 98.0% (Fig. 1). ROC AUC was 0.871 for the model and 0.867 for the risk score. Bootstrap validation (k=1000) led to an optimism-corrected AUC of 0.853 for the model and 0.849 for the score. Of all MIS patients, 17.4% (n=199) were at low risk (-1 and 0 points, 10.7 and 24.7% risk of SM), 14.5% (n=166) at medium risk (1 and 2 points, 47.1 and 70.7%) and 68.1% (n=779) at high risk (3-5 points, 86.8-98%).

Conclusion
Using a large data set of the ECNM registry, we created a risk score to better predict SM in patients with MIS. Although it will need validation in independent cohorts, our score seems to be valid and may discriminate between patients with SM and CM. Our new score may thus have clinical implications and may assist in the decision to recommend a BMB in adults with MIS.  

 

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Mast cell disease, Mastocytosis, Risk factor

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