Dataset Information

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

ABSTRACT: 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.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.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.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).

SUBMITTER: Wagner K

PROVIDER: S-EPMC3084914 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Wagner Katharina K Damm Frederik F Thol Felicitas F Göhring Gudrun G Görlich Kerstin K Heuser Michael M Schäfer Irina I Schlegelberger Brigitte B Heil Gerhard G Ganser Arnold A Krauter Jürgen J

Haematologica 20110117 5

<h4>Background</h4>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.<h4>Design and methods</h4>We analyzed 94 patients with acute myeloid leukemia and normal karyoty ...[more]

PMID: 21242187

Similar Datasets

Project description:FLT3-internal tandem duplication occurs in 20-30% of acute myeloid leukemia and confers an adverse prognosis with its allelic ratio being a key risk stratifier. The US Food and Drug Administration recently approved FLT3 inhibitors midostaurin and gilteritinib in FLT3 mutation-positive acute myeloid leukemia. Historically, FLT3 was tested by fragment analysis, which has become the standard method endorsed by international guidelines. However, next generation sequencing is increasingly used at acute myeloid leukemia diagnosis given its ability to simultaneously evaluate multiple clinically informative markers. As FLT3-internal tandem duplication detection was known to be challenging by next generation sequencing and the results carry profound prognostic and therapeutic implications, it is important to thoroughly examine its performance in FLT3-internal tandem duplication detection and allelic ratio classification. In a comparative study with fragment analysis, we retrospectively reviewed our experience using a custom-designed, hybridization capture-based, targeted next generation sequencing panel. Among 7902 cases, FLT3-internal tandem duplication was detected in 335 with variable sizes (3-231 bp) and insertion sites. Fragment analysis was also performed in 402 cases, demonstrating 100% concordance in FLT3-internal tandem duplication detection. In 136 dual-tested, positive cases, 128/136 (94%) exhibited concordant high/low allelic ratio classifications. The remaining 6% showed borderline low allelic ratio by next generation sequencing. The two methods were concordant in FLT3-tyrosine kinase domain mutation detection at the hotspot D835/I836 targeted by fragment analysis. Furthermore, seven mutations which may benefit from FLT3 inhibitor therapy were detected by next generation sequencing, in regions not covered by fragment analysis. Our study demonstrates that using a hybridization capture-based chemistry and optimized bioinformatics pipeline, next generation sequencing can reliably detect FLT3-internal tandem duplication and classify its allelic ratio for acute myeloid leukemia risk stratification. Next generation sequencing also exhibits superior comprehensiveness in FLT3 mutation detection and may further improve personalized, targeted therapy in acute myeloid leukemia.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets