The Presence of FLT3/ITD Mutations Is an Independent Prognostic Factor in Acute Myeloid Leukemia Patients with Normal Karyotype.

An internal tandem duplication of the FLT3 gene (FLT3/ITD) has been detected in approximately 20–30% of patients with acute myeloid leukemia (AML). These are frequently associated with poor outcome in AML patients, but it is still a matter of debate whether the FLT3/ITD mutations play a role in the prognosis of AML patients independently or not. We investigated the presence of FLT3/ITD mutation in 165 patients with de novo AML, except acute promyelocytic leukemia (APL), to evaluate its clinical and prognostic significance. The FLT3/ITD mutations were studied on bone marrow samples at diagnosis using PCR assay. Of the patients, 58 patients (35.2%) demonstrated the aberrant FLT3/ITD mutations. The patients with FLT3/ITD had significantly higher WBC counts at presentation compared with patients without FLT3/ITD (52.9 ± 66.9 ×10⁹/L vs. 32.4 ± 41.8 ×10⁹/L, p < 0.05). However, there was no statistically significant difference in age, gender, hemoglobin level, platelet count, percentage of peripheral or bone marrow blasts, or the presence of molecular abnormalities between the patients with FLT3/ITD and the patients without FLT3/ITD. To analyze the response to or outcome of therapy, we evaluated 118 patients who received intensive induction chemotherapy. In univariate analysis, there was no significant difference in complete response rate (p = 0.21), in median duration of overall survival (13.9±3.8 ms. vs. 16.5±0 ms., p = 0.07), or in median duration of leukemic-free survival (LFS) (9.8±3.5 ms. vs. 34.6±17.9 ms., p = 0.09) between the patients with FLT3/ITD and the patients without FLT3/ITD. However, the presence of FLT3/ITD was associated with lower LFS in the patients with a cytogenetically intermediate-risk group (p < 0.05). Furthermore, in multivariate analysis, FLT3/ITD mutations were an independent prognostic factor in LFS in AML patients with normal karyotype (p < 0.05). In conclusion, this study demonstrates that the presence of FLT3/ITD mutations is a significantly poor prognostic factor for leukemic free survival in non-APL patients with a cytogenetically intermediate-risk group, especially normal karyotype.