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

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). FLT3-ITD is associated with poor clinical outcome and is an indication for allogeneic stem cell transplantation (allo-SCT). METHODS: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. RESULTS: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.

journal_name

Eur J Haematol

authors

Schiller J,Praulich I,Krings Rocha C,Kreuzer KA

doi

10.1111/j.1600-0609.2012.01785.x

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

53-62

issue

1

eissn

0902-4441

issn

1600-0609

journal_volume

89

pub_type

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