TY - JOUR
T1 - Next-generation sequencing in systemic mastocytosis
T2 - Derivation of a mutation-augmented clinical prognostic model for survival
AU - Pardanani, Animesh D
AU - Lasho, Terra
AU - Elala, Yoseph
AU - Wassie, Emnet
AU - Finke, Christy
AU - Reichard, Kaaren K.
AU - Chen, Dong
AU - Hanson, Curtis A.
AU - Ketterling, Rhett P.
AU - Tefferi, Ayalew
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.24426
DO - 10.1002/ajh.24426
M3 - Article
C2 - 27214377
AN - SCOPUS:84983082799
SN - 0361-8609
VL - 91
SP - 888
EP - 893
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 9
ER -