FLT3-internal tandem duplication and age are the major prognostic factors in patients with relapsed acute myeloid leukemia with normal karyotype

Abstract

Background: Several genetic aberrations with prognostic impact in first-line therapy have been described in patients with acute myeloid leukemia and normal karyotype. However, little is known about the influence of these aberrations on outcome after relapse. This study aimed to identify clinical and molecular risk factors for patients with relapsed acute myeloid leukemia with normal karyotype.

Design and methods: We analyzed 94 patients with acute myeloid leukemia and normal karyotype after first relapse for clinical and molecular risk factors for survival. All patients had received first-line treatment and follow-up within two prospective, multicenter trials. Leukemic blasts were analyzed at diagnosis for genetic aberrations in the FLT3, NPM1, CEBPA, WT1, IDH1 and IDH2 genes by polymerase chain reaction and/or direct sequencing.

Results: A second complete remission was achieved in 52% of patients who received re-induction therapy. The presence of an FLT3-internal tandem duplication, duration of first complete remission less than 6 months and age above the median of 47 years were associated with a significantly lower rate of second complete remission. The median survival after relapse was 11 months and the 6-year survival rate was 28%. In multivariate analysis, FLT3-internal tandem duplication and age above the median were the only independent negative prognostic factors for survival. The 6-year survival rate of patients with none of these factors was 56%, whereas it was significantly inferior in patients with one or both of these factors (15% and 6%, respectively). This was also true for patients who underwent allogeneic stem cell transplantation after relapse.

Conclusions: FLT3-internal tandem duplication and age are the major prognostic factors in patients with relapsed acute myeloid leukemia with a normal karyotype. Patients with at least one of these risk factors have a dismal outcome and might be considered for investigational treatment approaches after relapse. (ClinicalTrials.gov Identifier: NCT00209833).

Figure 1.

(A) Survival after relapse for all patients. (B) Survival after relapse according to age. Solid line: patients <47 years (n=46); dotted line: patients ≥ 47 years (n=48); P=0.001. (C) Survival after disease according to FLT3-ITD. Solid line: patients without FLT3-ITD (n=64); dotted line: patients with FLT3-ITD (n=30); P=0.001.

Figure 2.

(A) Survival after relapse according to risk score. Solid line: patients without any risk factor (n=30); dotted line: patients with one risk factor (n=45); dashed line: patients with both risk factors (n=19); P<0.0001. (B) Survival after relapse according to risk score for patients who underwent allogeneic stem cell transplantation after relapse. Solid line: patients without any risk factor (n=19); dotted line: patients with one risk factor (n=27); dashed line: patients with both risk factors (n=5); P=0.022.