@article{Esther Onecha_Maria Linares_Inmaculada Rapado_Yanira Ruiz-Heredia_Pilar Martinez-Sanchez_Teresa Cedena_Marta Pratcorona_Jaime Perez Oteyza_Pilar Herrera_Eva Barragan_Pau Montesinos_Jose Antonio Garcia Vela_Elena Magro_Eduardo Anguita_Angela Figuera_Rosalia Riaza_Pilar Martinez-Barranco_Beatriz Sanchez-Vega_Josep Nomdedeu_Miguel Gallardo_Joaquin Martinez-Lopez_Rosa Ayala_2019, place={Pavia, Italy}, title={A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia}, volume={104}, url={https://haematologica.org/article/view/8771}, DOI={10.3324/haematol.2018.194712}, abstractNote={A high proportion of patients with acute myeloid leukemia who achieve minimal residual disease negative status ultimately relapse because a fraction of pathological clones remains undetected by standard methods. We designed and validated a high-throughput sequencing method for minimal residual disease assessment of cell clonotypes with mutations of <em>NPM1</em>, <em>IDH1/2</em> and/or <em>FLT3</em>-single nucleotide variants. For clinical validation, 106 follow-up samples from 63 patients in complete remission were studied by sequencing, evaluating the level of mutations detected at diagnosis. The predictive value of minimal residual disease status by sequencing, multiparameter flow cytometry, or quantitative polymerase chain reaction analysis was determined by survival analysis. The sequencing method achieved a sensitivity of 10<sup>−4</sup> for single nucleotide variants and 10<sup>−5</sup> for insertions/deletions and could be used in acute myeloid leukemia patients who carry any mutation (86% in our diagnostic data set). Sequencing–determined minimal residual disease positive status was associated with lower disease-free survival (hazard ratio 3.4, <em>P</em>=0.005) and lower overall survival (hazard ratio 4.2, <em>P</em><0.001). Multivariate analysis showed that minimal residual disease positive status determined by sequencing was an independent factor associated with risk of death (hazard ratio 4.54, <em>P</em>=0.005) and the only independent factor conferring risk of relapse (hazard ratio 3.76, <em>P</em&gt;=0.012). This sequencing-based method simplifies and standardizes minimal residual disease evaluation, with high applicability in acute myeloid leukemia. It is also an improvement upon flow cytometry- and quantitative polymerase chain reaction-based prediction of outcomes of patients with acute myeloid leukemia and could be incorporated in clinical settings and clinical trials.}, number={2}, journal={Haematologica}, author={Esther Onecha and Maria Linares and Inmaculada Rapado and Yanira Ruiz-Heredia and Pilar Martinez-Sanchez and Teresa Cedena and Marta Pratcorona and Jaime Perez Oteyza and Pilar Herrera and Eva Barragan and Pau Montesinos and Jose Antonio Garcia Vela and Elena Magro and Eduardo Anguita and Angela Figuera and Rosalia Riaza and Pilar Martinez-Barranco and Beatriz Sanchez-Vega and Josep Nomdedeu and Miguel Gallardo and Joaquin Martinez-Lopez and Rosa Ayala}, year={2019}, month={Jan.}, pages={288-296} }