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Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia
| Content Provider | Scilit |
|---|---|
| Author | Döhner, Konstanze Thiede, Christian Jahn, Nikolaus Panina, Ekaterina Gambietz, Agnes Larson, Richard A. Prior, Thomas W. Marcucci, Guido Jones, Dan Krauter, Jürgen Heuser, Michael Voso, Maria Teresa Ottone, Tiziana Nomdedeu, Josep F. Mandrekar, Sumithra J. Klisovic, Rebecca B. Wei, Andrew H. Sierra, Jorge Sanz, Miguel A. Brandwein, Joseph M. Witte, Theo M. De Jansen, Joop H. Niederwieser, Dietger Appelbaum, Frederick R. Medeiros, Bruno C. Tallman, Martin S. Schlenk, Richard F. Ganser, Arnold Serve, Hubert Ehninger, Gerhard Amadori, Sergio Gathmann, Insa Benner, Axel Pallaud, Celine Stone, Richard M. Döhner, Hartmut Bloomfield, Clara D. |
| Copyright Year | 2020 |
| Description | Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (≥0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 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, which evaluated the addition of midostaurin to standard chemotherapy. The 4 NPM1/FLT3-ITD genotypes differed significantly 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 1 or 2 induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly among 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 < .001). A 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993016/pdf |
| Ending Page | 380 |
| Page Count | 10 |
| Starting Page | 371 |
| DOI | 10.1182/blood.2019002697 |
| Journal | Blood |
| Issue Number | 5 |
| Volume Number | 135 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2020-01-30 |
| Access Restriction | Open |
| Subject Keyword | Hematology Treatment Survival Hematopoietic Model Eln Flt3 Itd Npm1/flt3 Journal: Blood (Vol- 85, Issue- 5) |
| Content Type | Text |
| Resource Type | Article |
