Variable prognostic value of FLT3 internal tandem duplications in patients with de novo AML and a normal karyotype, t(15;17), t(8;21) or inv(16)

Abstract

Introduction: Internal tandem duplication of the FLT3 gene (FLT3/ITD) has been linked to poor outcome in acute myeloid leukemia (AML). However, the prognostic value of FLT3/ITD in various cytogenetic risk groups is still a matter of debate. The aim of this study was to evaluate the prognostic significance in patients with de novo AML and a normal karyotype or a t(15;17), t(8;21) or inv(16) (good risk group).

Patients and methods: Diagnostic samples of 100 patients were investigated by single-step PCR of exons 11 and 12 of the FLT3 gene in a single center retrospective analysis. Subgroups included 53 patients with normal karyotype, 21 patients with t(15;17), 9 patients with t(8;21) and 17 patients with inv(16).

Results: FLT3/ITD was found in 26 out of 100 patients: 30% of patients with a normal karyotype and 38% of t(15;17) patients tested positive. The complete remission (CR) rates for the ITD(+) or ITD(-) groups were 50 vs 76% in normal karyotypes, and 100 vs 53% in t(15;17) patients, while the relapse rates were 75 vs 25% in normal karyotypes and 50 vs 42% in t(15;17) patients. Overall survival (OS) and disease free survival (DFS) at 5 years were significantly different in patients with normal cytogenetics: ITD(+) vs ITD(-): OS 6 vs 28% (P<0.003); DFS 13 vs 41% (P<0.02) Interestingly, FLT3/ITD had no significant effect on the outcome of t(15;17) patients: ITD(+) vs ITD(-): OS 85 vs 53% (P=0.056), DFS 45 vs 60% (P=0.6) at 50 months.

Conclusions: These data suggest a high prognostic value of FLT3/ITD in patients with normal cytogenetics. However, we find no evidence that FLT3/ITD is a predictive marker for patients with t(15;17).