Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia.
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Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia. / Schnittger, S; Bacher, Ulrike; Kern, W; Alpermann, T; Haferlach, C; Haferlach, T.
In: LEUKEMIA, Vol. 25, No. 8, 8, 2011, p. 1297-1304.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia.
AU - Schnittger, S
AU - Bacher, Ulrike
AU - Kern, W
AU - Alpermann, T
AU - Haferlach, C
AU - Haferlach, T
PY - 2011
Y1 - 2011
N2 - High FLT3-ITD/wildtype (wt) load in FLT3-ITD-mutated AML has been associated with adverse impact on outcome in several studies. To clarify whether FLT3-ITD load as expressed as FLT3-ITD/wt ratio is also relevant in patients with NPM1 mutated AML, we assessed the FLT3-ITD mutation status and FLT3-ITD/wt ratio by fragment analysis in 638 NPM1mut AML (339 females; 299 males; 17.8-88.0 years), and analyzed its prognostic relevance in 355 patients. FLT3-ITD of various length and load were detected in 243/638 cases (38.1%). Median EFS (19.3 vs 9.7 months, P<0.001) and median 2-year survival rate (72.0 vs 52.7%, P=0.006) was better in FLT3wt (n=212 with available follow-up data) than FLT3-ITD (n=143). A higher FLT3-ITD/wt ratio as continuous variable was correlated with a shorter EFS (P=0.028). When patients were separated into subgroups according to the FLT3-ITD mutation load, only a FLT3-ITD/wt ratio ?0.5 conferred an independent adverse impact on EFS and OS, and retained its prognostic significance also in multivariate analysis (P=0.009 for EFS, P=0.008 for OS). In conclusion, for risk estimation in NPM1 mutated AML not only the FLT3-ITD status, but also the FLT3-ITD load has to be taken into account. These data might contribute to clinical decision making in AML.
AB - High FLT3-ITD/wildtype (wt) load in FLT3-ITD-mutated AML has been associated with adverse impact on outcome in several studies. To clarify whether FLT3-ITD load as expressed as FLT3-ITD/wt ratio is also relevant in patients with NPM1 mutated AML, we assessed the FLT3-ITD mutation status and FLT3-ITD/wt ratio by fragment analysis in 638 NPM1mut AML (339 females; 299 males; 17.8-88.0 years), and analyzed its prognostic relevance in 355 patients. FLT3-ITD of various length and load were detected in 243/638 cases (38.1%). Median EFS (19.3 vs 9.7 months, P<0.001) and median 2-year survival rate (72.0 vs 52.7%, P=0.006) was better in FLT3wt (n=212 with available follow-up data) than FLT3-ITD (n=143). A higher FLT3-ITD/wt ratio as continuous variable was correlated with a shorter EFS (P=0.028). When patients were separated into subgroups according to the FLT3-ITD mutation load, only a FLT3-ITD/wt ratio ?0.5 conferred an independent adverse impact on EFS and OS, and retained its prognostic significance also in multivariate analysis (P=0.009 for EFS, P=0.008 for OS). In conclusion, for risk estimation in NPM1 mutated AML not only the FLT3-ITD status, but also the FLT3-ITD load has to be taken into account. These data might contribute to clinical decision making in AML.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Adolescent
KW - Multivariate Analysis
KW - Age Factors
KW - Prognosis
KW - Nuclear Proteins/genetics
KW - Mutation
KW - Leukemia, Myeloid, Acute/genetics/mortality
KW - fms-Like Tyrosine Kinase 3/chemistry/physiology
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Adolescent
KW - Multivariate Analysis
KW - Age Factors
KW - Prognosis
KW - Nuclear Proteins/genetics
KW - Mutation
KW - Leukemia, Myeloid, Acute/genetics/mortality
KW - fms-Like Tyrosine Kinase 3/chemistry/physiology
M3 - SCORING: Journal article
VL - 25
SP - 1297
EP - 1304
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 8
M1 - 8
ER -
