BACKGROUND: Combined 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 METHODS: To 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. RESULTS: Internal 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 10×10(9)/L or less versus more than 10×10(9)/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. CONCLUSIONS: Prospective 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.
BACKGROUND: Combined 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 METHODS: To 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. RESULTS: Internal 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 10×10(9)/L or less versus more than 10×10(9)/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. CONCLUSIONS: Prospective 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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