Abstract AML patients under the age of 60 whose blasts harbor a FLT3 internal tandem duplication (ITD) mutation have a higher relapse rate and inferior survival compared to those without this ...mutation. To determine if FLT3ITD also carries a negative prognostic impact in older adults receiving therapies commonly used in this age group, we retrospectively analyzed outcomes of patients ≥60 years with CN-AML according to FLT3 mutation status. We identified 91 newly diagnosed CN-AML patients, 55 with wild-type FLT3 and 36 with FLT3ITD. Of the 91 patients, 36 received supportive care and/or experimental therapies while the remaining 55 received induction chemotherapy, followed by allogeneic SCT in 17 of these patients. Based on univariate analysis, advanced age at diagnosis was significantly associated with shorter overall survival (OS) ( p < .0001) while intensive therapies were associated with improved OS ( p < .0001). In a multivariate analysis that accounted for type of treatment, patient age, gender, and WBC count, FLT3ITD was significantly associated with shorter OS compared to wtFLT3 p = .001; hazard ratio (HR) = 2.23; 95% CI: 1.35–3.70. Our data support the negative prognostic impact of FLT3ITD in older adults with CN-AML.
We retrospectively analyzed clinical outcomes of patients aged 18–59 with cytogenetically normal AML (CN-AML) and mutations in the FLT3 receptor according to type of postremission therapy. ...Specifically, we compared the outcomes of patients who underwent autologous SCT versus consolidation chemotherapy. There were 37 patients with an ITD mutation (7 also had a TKD mutation) and 19 patients with an isolated TKD mutation at diagnosis. In all, patients with an isolated TKD (n=16) had an improved DFS and OS (p=.031 and .014, respectively) compared to ITD patients (n=21). For individuals with an isolated TKD mutation, survival outcomes were similar irrespective of the type of postremission therapy (n=7 for SCT and 9 for chemotherapy) (p=0.97 and 0.082, respectively). However, ITD positive patients who underwent an SCT in CR1 (n=10) had an improved DFS but similar OS compared to those who received consolidation chemotherapy (n=11) (p=.05 and .27). These results suggest that high dose chemotherapy with autologous SCT may be a reasonable therapeutic choice over consolidation chemotherapy for young CN-AML patients with a FLT3ITD mutation.
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