WEN-CHIEN CHOUHSIN-AN HOULiu C.-Y.Chen C.-Y.LIANG-IN LINHuang Y.-N.Chao Y.-C.Hsu C.-A.Huang C.-F.HWEI-FANG TIEN2020-06-162020-06-1620110923-7534https://scholars.lib.ntu.edu.tw/handle/123456789/502695Background: The level of minimal residual disease (MRD) in acute myeloid leukemia (AML) at early time points (TPs) may be an important prognostic factor. Although internal tandem duplication of FLT3 (FLT3-ITD) as an MRD marker has been questioned for its instability based on semi-quantitative methods, we hypothesized that FLT3-ITD dynamics measured by sensitive quantitative real-time PCR at early TPs before appearance of instability may provide prognostic information. Patients and methods: We measured mutant quantity in 493 serial samples from 55 patients with a median followup time of 64.8 months. The FLT3-ITD quantities after induction (TP1) and after the first post-induction chemotherapy (TP2) were analyzed. Results: We found that lower FLT3-ITD levels at TP2 predicted longer overall survival (OS) and disease-free survival (DFS) regardless of cytogenetic risk. Multivariate analysis showed that ?3 log reduction of FLT3-ITD at TP2 independently predicted better DFS and a trend toward better OS. FLT3-ITD disappeared at relapse in 16.7% of patients and none in those harboring mutant NPM1 compared with 29.4% in those with wild-type NPM1 (P = 0.032). Conclusions: Though the mutation may disappear at relapse in a few patients, FLT3-ITD levels at early TPs after chemotherapy provide prognostic information. FLT3-ITD is significantly more stable in those with mutant NPM1. ? The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.[SDGs]SDG3anthracycline; CD135 antigen; cytarabine; doxorubicin; idarubicin; nucleophosmin; retinoic acid; acute granulocytic leukemia; adolescent; adult; aged; article; cancer chemotherapy; cancer relapse; cancer survival; controlled study; disease free survival; drug megadose; female; gene duplication; gene mutation; genetic marker; human; internal tandem duplication; major clinical study; male; minimal residual disease; molecular dynamics; multiple cycle treatment; nucleotide sequence; outcome assessment; overall survival; priority journal; prognosis; quantitative study; sensitivity analysis; trend study; wild type; Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Disease-Free Survival; Female; fms-Like Tyrosine Kinase 3; Genetic Association Studies; Genetic Markers; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Middle Aged; Molecular Sequence Data; Multivariate Analysis; Mutagenesis, Insertional; Neoplasm, Residual; Nuclear Proteins; Prognosis; Sequence Analysis, DNA; Young Adultjournal article10.1093/annonc/mdq402206932962-s2.0-79953847289