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.
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.
Authors: Craig E Eckfeldt; Nicole Randall; Ryan M Shanley; Sophia Yohe; Nelli Bejanyan; Michelle Dolan; Erica D Warlick; Michael R Verneris; Claudio G Brunstein; John E Wagner; Daniel J Weisdorf; Celalettin Ustun Journal: Haematologica Date: 2016-04-28 Impact factor: 9.941
Authors: Sameh Gaballa; Rima Saliba; Betul Oran; Jonathan E Brammer; Julianne Chen; Gabriela Rondon; Amin M Alousi; Partow Kebriaei; David Marin; Uday R Popat; Borje S Andersson; Elizabeth J Shpall; Elias Jabbour; Naval Daver; Michael Andreeff; Farhad Ravandi; Jorge Cortes; Keyur Patel; Richard E Champlin; Stefan O Ciurea Journal: Am J Hematol Date: 2017-02-13 Impact factor: 10.047
Authors: Michael R Grunwald; Li-Hui Tseng; Ming-Tseh Lin; Keith W Pratz; James R Eshleman; Mark J Levis; Christopher D Gocke Journal: Biol Blood Marrow Transplant Date: 2014-08-23 Impact factor: 5.742
Authors: Ming-Tseh Lin; Li-Hui Tseng; Jonathan C Dudley; Stacey Riel; Harrison Tsai; Gang Zheng; Keith W Pratz; Mark J Levis; Christopher D Gocke Journal: Mol Diagn Ther Date: 2015-12 Impact factor: 4.074