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Patient‐specific analysis of FLT3 internal tandem duplications for the prognostication and monitoring of acute myeloid leukemia

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Abstract
Objectives

Internal tandem duplications (ITDs) of the fms‐like tyrosine kinase 3 ( FLT3) gene occur in 13–35% of patients with acute myeloid leukemia (AML). FLT3ITD is associated with poor clinical outcome and is an indication for allogeneic stem cell transplantation (allo‐SCT).
Methods

To investigate FLT3ITD length, position, and mutational load in AML cases, we developed patient‐specific quantitative real‐time reverse transcription polymerase chain reaction (qRTPCR) assays and correlated the results with established sensitive minimal residual disease (MRD) parameters and clinical outcome.
Results

In 409 patients with AML, FLT3ITDs could be detected in 54 cases (13%). Within our cohort, patients with FLT3ITD ≥45 base pairs had significantly higher relapse rates (= 0.03) and a worse overall survival (= 0.03). Our method could be applied to 97% of FLT3ITD‐positive patients and was as sensitive as other MRD parameters such as PMLRARA , NPM1 mutations, or MLL PTD (correlation: r = 0.63; 0.99, and 0.99, respectively). MRD negativity predicted lasting remission independent of allo‐SCT (= 7) or non‐allo‐SCT (= 9). All paired diagnostic/relapsed samples showed FLT3ITD positivity. Compared with bone marrow samples, FLT3ITD analyses appeared to be equivalently sensitive in peripheral blood.
Conclusions

We conclude that individualized monitoring of FLT3ITD in patients with AML may guide treatment decisions and should be evaluated for the indication for allo‐SCT.
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Document Type: Research Article

Publication date: July 1, 2012

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