The role of FLT3 in sole trisomy 8 acute myeloid leukemia.

Abstract

6562 Background: FLT3 (fms-related tyrosine kinase 3) with internal tandem duplication (ITD) is a known adverse prognostic factor in normal karyotype acute myeloid leukemia (AML). We asked whether FLT3 ITD carries any prognostic significance in sole trisomy 8 AML. Methods: A total of 37 AML patients (25 males:12 females) with sole trisomy 8 were seen at Roswell Park Cancer Institute between 1991 and 2008. Treatment differed according to available protocols at the time. Results: Nucleophosmin (NPM1) was detected in only one case (FLT3 ITD/D835 negative). Interestingly, FLT3 D835 was detected in five (20%) of the 25 patients without FLT3 ITD but was not detected in any of the 7 FLT3 ITD- positive patients. A total of 22 (59%) patients achieved complete remission (CR). There was no difference in achievement of CR, overall or disease-free survival between trisomy 8 patients with or without FLT3 ITD. Of interest, patients with FLT3 ITD were significantly younger (mean: 50 year old; 95% confidence interval [CI]: 33.51, 66.49) compared to patients without FLT3 ITD (mean: 69.8 year old; 95% CI: 65.87, 73.73) (p = 0.006). In addition, patients with FLT3 ITD were less likely to have normal metaphases in their karyotype than patients without FLT3 ITD (86.7% [95% CI: 0.693, 0.963] vs. 42.8% [95% CI: 0.099, 0.816]; p = 0.027). Conclusions: The presence of FLT3 ITD in trisomy 8 AML was associated with younger age and presence of trisomy 8 in all analyzed metaphases when compared to those without FLT3 ITD. AML patients with trisomy 8 and FLT3 ITD had similar CR, overall and progression-free survival as those without FLT3 ITD. No significant financial relationships to disclose.