Internal tandem duplications (ITDs) of the fms‐like tyrosine kinase 3 ( FLT3) gene
occur in 13–35% of patients with acute myeloid leukemia (AML). FLT3‐ITD is associated with poor clinical outcome and is an indication for allogeneic stem cell transplantation (allo‐SCT).
To investigate FLT3‐ITD length, position, and mutational load in AML cases, we developed patient‐specific
quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR) assays and correlated the results with established sensitive minimal residual disease (MRD) parameters and clinical outcome.
In 409 patients with AML, FLT3‐ITDs could be detected in 54 cases (13%). Within our cohort, patients with FLT3‐ITD
≥45 base pairs had significantly higher relapse rates (P = 0.03) and a worse overall survival (P = 0.03). Our method could be applied to 97% of FLT3‐ITD‐positive patients and
was as sensitive as other MRD parameters such as PML‐RARA , NPM1 mutations, or MLL ‐PTD (correlation: r = 0.63;
0.99, and 0.99, respectively). MRD negativity predicted lasting remission independent of allo‐SCT (N = 7) or non‐allo‐SCT (N = 9). All paired diagnostic/relapsed
samples showed FLT3‐ITD positivity. Compared with bone marrow samples, FLT3‐ITD analyses appeared to be equivalently sensitive in peripheral blood. Conclusions
We conclude that individualized monitoring of FLT3‐ITD 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
July 1, 2012