title: Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival.
abstract: In routine practice, the World Health Organization classification of systemic mastocytosis (SM) is also the de facto prognostic system; a core value is distinguishing indolent (ISM) from advanced SM (includes aggressive SM [ASM], SM with associated hematological neoplasm [SM-AHN] and mast cell leukemia [MCL]). We sequenced 27 genes in 150 SM patients to identify mutations that could be integrated into a clinical-molecular prognostic model for survival. Forty four patients (29%) had ISM, 25 (17%) ASM, 80 (53%) SM-AHN and 1 (0.7%) MCL; overall KITD816V prevalence was 75%. In 87 patients, 148 non-KIT mutations were detected; the most frequently mutated genes were TET2 (29%), ASXL1 (17%), and CBL (11%), with significantly higher mutation frequency in SM-AHN > ASM > ISM (P < 0.0001). In advanced SM, ASXL1 and RUNX1 mutations were associated with inferior survival. In multivariate analysis, age > 60 years (HR = 2.4), hemoglobin < 10 g/dL or transfusion-dependence (HR = 1.7), platelet count < 150 × 10(9) /L (HR = 3.2), serum albumin < 3.5 g/dL (HR = 2.6), and ASXL1 mutation (HR = 2.3) were associated with inferior survival. A mutation-augmented prognostic scoring system (MAPSS) based on these parameters stratified advanced SM patients into high-, intermediate-, and low-risk groups with median survival of 5, 21 and 86 months, respectively (P < 0.0001). These data should optimize risk-stratification and treatment selection for advanced SM patients. Am. J. Hematol. 91:888-893, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Terra
authors.initials: T
authors.lastname: Lasho
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Elala
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Emnet
authors.initials: E
authors.lastname: Wassie
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Christy
authors.initials: C
authors.lastname: Finke
authors.affiliation: Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kaaren K
authors.initials: KK
authors.lastname: Reichard
authors.affiliation: Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Department of Laboratory Medicine and Pathology, Division of Cytogenetics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D034721:Mastocytosis, Systemic / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D008962:Models, Theoretical; D009154:Mutation; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate; D055815:Young Adult