Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival

Animesh Pardanani, Terra Lasho, Yoseph Elala, Emnet Wassie, Christy Finke, Kaaren K. Reichard, Dong Chen, Curtis A. Hanson, Rhett P. Ketterling, Ayalew Tefferi

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 × 109/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.

Original languageEnglish (US)
Pages (from-to)888-893
Number of pages6
JournalAmerican journal of hematology
Volume91
Issue number9
DOIs
StatePublished - Sep 1 2016

ASJC Scopus subject areas

  • Hematology

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