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. 2013 May 24;3(5):e116.
doi: 10.1038/bcj.2013.14.

The prognostic impact of FLT3-ITD and NPM1 mutations in patients with relapsed acute myeloid leukemia and intermediate-risk cytogenetics

J How  1 , J Sykes, M D Minden, V Gupta, K W L Yee, A D Schimmer, A C Schuh, S Kamel-Reid, J M Brandwein
Affiliations

The prognostic impact of FLT3-ITD and NPM1 mutations in patients with relapsed acute myeloid leukemia and intermediate-risk cytogenetics

J How et al. Blood Cancer J. .

Abstract

Internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations have prognostic importance in acute myeloid leukemia (AML) patients with intermediate-risk karyotype at diagnosis, but less is known about their utility to predict outcomes at relapse. We retrospectively analysed outcomes of 70 patients with relapsed, intermediate-risk karyotype AML who received a uniform reinduction regimen, with respect to FLT3-ITD and NPM1 mutation status and first complete remission (CR1) duration. CR1 duration, but not molecular status, was significantly correlated with CR2 rate. On univariate analysis, patients with mutated FLT3-ITD (FLT3+) had significantly worse overall survival (OS) compared with those with neither an NPM1 nor FLT3-ITD mutation (NPM1-/FLT3-). On multivariate analysis, shorter CR1 duration was significantly correlated with inferior OS at relapse (P<0.0001), while FLT3 and NPM1 mutation status and age were not significantly correlated with OS. Patients who subsequently underwent allogeneic stem cell transplant (alloSCT) had a superior OS regardless of CR1 duration, but outcomes were better in patients with CR1 duration>12 months. In intermediate-risk karyotype AML patients receiving reinduction, CR1 duration remains the most important predictor of OS at relapse; FLT3-ITD and NPM1 status are not independent predictors of survival.

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Figures

Figure 1
Figure 1
OS from time of relapse, according to mutation status, for the 70 patients who underwent reinduction.
Figure 2
Figure 2
OS from time of relapse, according to CR1 duration, for the 70 patients who underwent reinduction.
Figure 3
Figure 3
Outcome of the 42 patients who achieved CR2, according to CR1 duration and whether alloSCT was performed in CR2.
See this image and copyright information in PMC

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