Molecular Minimal Residual Disease in Acute Myeloid Leukemia
| Autor: | Patrycja L Gradowska, Tim Grob, Carlos Graux, Diana Hanekamp, Violaine Havelange, Adil Al Hinai, François G. Kavelaars, Mojca Jongen-Lavrencic, Marinus van Marwijk Kooy, Annelieke Zeilemaker, Bart J. Biemond, Bob Löwenberg, Mathijs A. Sanders, Markus G. Manz, Jakob Passweg, Rosa Meijer, Gerrit Jan Schuurhuis, Jacqueline Cloos, Gert J. Ossenkoppele, Peter J. M. Valk, Claudia A.J. Erpelinck-Verschueren, Thomas Pabst |
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| Přispěvatelé: | Hematology laboratory, CCA - Cancer biology and immunology, Hematology, AII - Inflammatory diseases, Clinical Haematology, University of Zurich, Valk, Peter J M, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service d'hématologie, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Neoplasm Residual Myeloid Adolescent DNA Mutational Analysis 610 Medicine & health 2700 General Medicine Young Adult 03 medical and health sciences 0302 clinical medicine Recurrence Internal medicine medicine Humans Survival analysis Aged Proportional Hazards Models business.industry Proportional hazards model Remission Induction Hazard ratio High-Throughput Nucleotide Sequencing Cancer Myeloid leukemia DNA Neoplasm General Medicine Middle Aged Flow Cytometry Prognosis medicine.disease Survival Analysis Minimal residual disease Hematopoiesis Leukemia Myeloid Acute Leukemia 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Mutation 10032 Clinic for Oncology and Hematology Female business |
| Zdroj: | Jongen-Lavrencic, Mojca; Grob, Tim; Hanekamp, Diana; Kavelaars, François G; Al Hinai, Adil; Zeilemaker, Annelieke; Erpelinck-Verschueren, Claudia A J; Gradowska, Patrycja L; Meijer, Rosa; Cloos, Jacqueline; Biemond, Bart J; Graux, Carlos; van Marwijk Kooy, Marinus; Manz, Markus G; Pabst Müller, Thomas Niklaus; Passweg, Jakob R; Havelange, Violaine; Ossenkoppele, Gert J; Sanders, Mathijs A; Schuurhuis, Gerrit J; ... (2018). Molecular Minimal Residual Disease in Acute Myeloid Leukemia. New England journal of medicine NEJM, 378(13), pp. 1189-1199. Massachusetts Medical Society MMS 10.1056/NEJMoa1716863 New England Journal of Medicine, 378(13), 1189-1199. Massachussetts Medical Society New England journal of medicine, 378(13), 1189-1199. Massachussetts Medical Society Jongen-Lavrencic, M, Grob, T, Hanekamp, D, Kavelaars, F G, Al Hinai, A, Zeilemaker, A, Erpelinck-Verschueren, C A J, Gradowska, P L, Meijer, R, Cloos, J, Biemond, B J, Graux, C, van Marwijk Kooy, M, Manz, M G, Pabst, T, Passweg, J R, Havelange, V, Ossenkoppele, G J, Sanders, M A, Schuurhuis, G J, Löwenberg, B & Valk, P J M 2018, ' Molecular Minimal Residual Disease in Acute Myeloid Leukemia ', New England Journal of Medicine, vol. 378, no. 13, pp. 1189-1199 . https://doi.org/10.1056/NEJMoa1716863 The New England journal of medicine, Vol. 378, no. 13, p. 1189-1199 (2018) |
| ISSN: | 0028-4793 |
| DOI: | 10.1056/NEJMoa1716863 |
| Popis: | BACKGROUND: Patients with acute myeloid leukemia (AML) often reach complete remission, but relapse rates remain high. Next-generation sequencing enables the detection of molecular minimal residual disease in virtually every patient, but its clinical value for the prediction of relapse has yet to be established.METHODS: We conducted a study involving patients 18 to 65 years of age who had newly diagnosed AML. Targeted next-generation sequencing was carried out at diagnosis and after induction therapy (during complete remission). End points were 4-year rates of relapse, relapse-free survival, and overall survival.RESULTS: At least one mutation was detected in 430 out of 482 patients (89.2%). Mutations persisted in 51.4% of those patients during complete remission and were present at various allele frequencies (range, 0.02 to 47%). The detection of persistent DTA mutations (i.e., mutations in DNMT3A, TET2, and ASXL1), which are often present in persons with age-related clonal hematopoiesis, was not correlated with an increased relapse rate. After the exclusion of persistent DTA mutations, the detection of molecular minimal residual disease was associated with a significantly higher relapse rate than no detection (55.4% vs. 31.9%; hazard ratio, 2.14; PCONCLUSIONS: Among patients with AML, the detection of molecular minimal residual disease during complete remission had significant independent prognostic value with respect to relapse and survival rates, but the detection of persistent mutations that are associated with clonal hematopoiesis did not have such prognostic value within a 4-year time frame. (Funded by the Queen Wilhelmina Fund Foundation of the Dutch Cancer Society and others.). |
| Databáze: | OpenAIRE |
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