Clinical impact of FLT3 mutation load in acute promyelocytic leukemia with t(15;17)/PML-RARA |
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Authors: | Schnittger Susanne Bacher Ulrike Haferlach Claudia Kern Wolfgang Alpermann Tamara Haferlach Torsten |
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Affiliation: | MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, Munich, Germany. susanne.schnittger@mll.com |
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Abstract: | BackgroundCombined treatment with all-trans-retinoic acid and chemotherapy is extremely efficient in patients with acute promyelocytic leukemia with t(15;17)/PML-RARA, but up to 15% of patients relapse.Design and MethodsTo further clarify the prognostic impact of parameters such as FLT3 mutations, we comprehensively characterized the relation between genetic features and outcome in 147 patients (aged 19.7–86.3 years) with acute promyelocytic leukemia.ResultsInternal tandem duplications of the FLT3 gene (FLT3-ITD) were detected in 47/147 (32.0%) and tyrosine kinase domain mutations (FLT3-TKD) in 19/147 (12.9%) patients. FLT3-ITD or FLT3-TKD mutation status did not have a significant prognostic impact, whereas FLT3-ITD mutation load, as defined by a mutation/wild-type ratio of less than 0.5 was associated with trends to a better 2-year overall survival rate (86.7% versus 72.7%; P=0.075) and 2-year event-free survival rate (84.5% versus 62.1%, P=0.023) compared to the survival rates of patients with a ratio of 0.5 or more. Besides the t(15;17), an additional chromosomal abnormality was detected in 57 of 147 cases and did not show a significant impact on survival. White blood cell counts of 10×109/L or less versus more than 10×109/L were associated with a better 2-year overall survival rate (88.3% versus 69.4%, respectively; P=0.015), as was male sex (P=0.040). In multivariate analysis, only higher age had a significant adverse impact.ConclusionsProspective trials should further investigate the clinical impact of the FLT3-ITD/wild-type mutation load aiming to evaluate whether this parameter might be included in risk stratification in patients with acute promyelocytic leukemia. |
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Keywords: | acute promyelocytic leukemia FLT3 mutations FLT3-ITD/wt ratio additional chromosomal alterations prognosis |
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