title: Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis.
abstract: We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced systemic mastocytosis (SM) (advSM, n=67). Organomegaly was measured by magnetic resonance imaging-based volumetry of the liver and spleen. In multivariate analysis of all patients, an increased spleen volume ⩾450 ml (hazard ratio (HR), 5.2; 95% confidence interval (CI), (2.1-13.0); P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 (1.1-22.2); P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P<0.0001), for patients with 0 (low risk, n=37), 1 (intermediate risk, n=32) or 2 (high risk, n=39) parameters. For advSM patients with fully available clinical and molecular data (n=60), univariate analysis identified splenomegaly ⩾1200 ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR 3.2 (1.1-9.6); P=0.01) and elevated AP (HR 2.6 (1.0-7.1); P=0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76 and 38%, respectively (P=0.0003), for patients with 0-1 (intermediate risk, n=28) or 2 (high risk, n=32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the World Health Organization classification and provide the most relevant prognostic information in SM patients.
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Jawhar
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schwaab
authors.affiliation: Institute of Clinical Radiology and Nuclear Medicine, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Hausmann
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Clemens
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Naumann
authors.affiliation: Institute of Clinical Radiology and Nuclear Medicine, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Henzler
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: H-P
authors.initials: HP
authors.lastname: Horny
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Sotlar
authors.affiliation: Institute of Clinical Radiology and Nuclear Medicine, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: S O
authors.initials: SO
authors.lastname: Schoenberg
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury, UK.|Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: N C P
authors.initials: NC
authors.lastname: Cross
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Fabarius
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: W-K
authors.initials: WK
authors.lastname: Hofmann
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Valent
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Metzgeroth
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Reiter
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D034721:Mastocytosis, Systemic / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics*; D013163:Splenomegaly / Q000000981:diagnostic imaging / Q000473:pathology*; D015996:Survival Rate
chemical_list: C473949:ASXL1 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; D012097:Repressor Proteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D000469:Alkaline Phosphatase