Next‐generation sequencing in systemic mastocytosis: Derivation of a mutation‐augmented clinical prognostic model for survival. Issue 9 (20th June 2016)

• Record Type: Journal Article
• Authors: Pardanani, Animesh; Lasho, Terra; Elala, Yoseph; Wassie, Emnet; Finke, Christy; Reichard, Kaaren K.; Chen, Dong; Hanson, Curtis A.; Ketterling, Rhett P.; Tefferi, Ayalew
• Is Part Of: American journal of hematology. Volume 91:Issue 9(2016:Sep.)
• Page Start: 888
• Page End: 893
• Publication Date: 2016-06-20
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24426
• Languages: English
• ISSNs: 0361-8609

Abstract

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 KIT D816V 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.