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EnglishPatients with AML harboring FLT3 internal tandem duplications (ITD) have poor outcomes, in particular AML with a high (greater than or equal to0.5) mutant-to-wildtype allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined four distinct FLT3-ITD genotypes based on the ITD-AR and the NPM1 mutational status. In this retrospective, exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial evaluating the addition of midostaurin to standard chemotherapy. The four NPM1/FLT3-ITD genotypes significantly differed with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after one or two induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly between ELN risk groups with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate- and adverse-risk groups, respectively (P<0.001). Multivariate Cox model for OS using allogeneic hematopoietic-cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.
Döhner, K., Thiede, C., Jahn, N., Panina, E., Gambietz, A., Larson, R.A., et al. (2020). Impact of NPM1/FLT3-ITD genotypes defined by the2017 European LeukemiaNet in patients with acute myeloid leukemia. BLOOD, 135(5), 371-380 [10.1182/blood.2019002697].
| Tipologia: | Articolo su rivista | |
| Citazione: | Döhner, K., Thiede, C., Jahn, N., Panina, E., Gambietz, A., Larson, R.A., et al. (2020). Impact of NPM1/FLT3-ITD genotypes defined by the2017 European LeukemiaNet in patients with acute myeloid leukemia. BLOOD, 135(5), 371-380 [10.1182/blood.2019002697]. | |
| Lingua: | English | |
| Settore Scientifico Disciplinare: | Settore MED/15 - Malattie del Sangue | |
| Revisione (peer review): | Esperti anonimi | |
| Tipo: | Articolo | |
| Rilevanza: | Rilevanza internazionale | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1182/blood.2019002697 | |
| Stato di pubblicazione: | Pubblicato | |
| Data di pubblicazione: | 11-dic-2020 | |
| Titolo: | Impact of NPM1/FLT3-ITD genotypes defined by the2017 European LeukemiaNet in patients with acute myeloid leukemia | |
| Autori: | ||
| Autori: | Döhner, K; Thiede, C; Jahn, N; Panina, E; Gambietz, A; Larson, RA; Prior, TW; Marcucci, G; Jones, D; Krauter, J; Heuser, M; Voso, MT; Ottone, T; Nomdedeu, JF; Mandrekar, SJ; Klisovic, R; Wei, AH; Sierra, J; Sanz, MA; Brandwein, J; de Witte, TM; Jansen, JH; Niederwieser, D; Appelbaum, F; Medeiros, BC; Tallman, MS; Schlenk, RF; Ganser, A; Serve, H; Ehninger, G; Amadori, S; Gathmann, I; Benner, A; Pallaud, C; Stone, RM; Döhner, H; Bloomfield, CD | |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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