Literature DB >> 21696826

Outcome of older adults with cytogenetically normal AML (CN-AML) and FLT3 mutations.

Harshabad Singh1, Salma Asali, Lillian L Werner, Daniel J DeAngelo, Karen K Ballen, Philip C Amrein, Martha Wadleigh, Ilene Galinsky, Donna S Neuberg, Edward A Fox, Richard M Stone, Eyal C Attar.   

Abstract

AML patients under the age of 60 whose blasts harbor a FLT3 internal tandem duplication (ITD) mutation have a higher relapse rate and inferior survival compared to those without this mutation. To determine if FLT3ITD also carries a negative prognostic impact in older adults receiving therapies commonly used in this age group, we retrospectively analyzed outcomes of patients ≥60 years with CN-AML according to FLT3 mutation status. We identified 91 newly diagnosed CN-AML patients, 55 with wild-type FLT3 and 36 with FLT3ITD. Of the 91 patients, 36 received supportive care and/or experimental therapies while the remaining 55 received induction chemotherapy, followed by allogeneic SCT in 17 of these patients. Based on univariate analysis, advanced age at diagnosis was significantly associated with shorter overall survival (OS) (p<.0001) while intensive therapies were associated with improved OS (p<.0001). In a multivariate analysis that accounted for type of treatment, patient age, gender, and WBC count, FLT3ITD was significantly associated with shorter OS compared to wtFLT3 [p=.001; hazard ratio (HR)=2.23; 95% CI: 1.35-3.70]. Our data support the negative prognostic impact of FLT3ITD in older adults with CN-AML. Copyright Â
© 2011 Elsevier Ltd. All rights reserved.

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Year:  2011        PMID: 21696826      PMCID: PMC3498766          DOI: 10.1016/j.leukres.2011.05.032

Source DB:  PubMed          Journal:  Leuk Res        ISSN: 0145-2126            Impact factor:   3.156


  21 in total

1.  FLT3 mutation and response to intensive chemotherapy in young adult and elderly patients with normal karyotype.

Authors:  Miloslav Beran; Rajyalakshmi Luthra; Hagop Kantarjian; Elihu Estey
Journal:  Leuk Res       Date:  2004-06       Impact factor: 3.156

2.  Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis.

Authors:  Christian Thiede; Christine Steudel; Brigitte Mohr; Markus Schaich; Ulrike Schäkel; Uwe Platzbecker; Martin Wermke; Martin Bornhäuser; Markus Ritter; Andreas Neubauer; Gerhard Ehninger; Thomas Illmer
Journal:  Blood       Date:  2002-06-15       Impact factor: 22.113

3.  FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia.

Authors:  D L Stirewalt; K J Kopecky; S Meshinchi; F R Appelbaum; M L Slovak; C L Willman; J P Radich
Journal:  Blood       Date:  2001-06-01       Impact factor: 22.113

Review 4.  Acute myeloid leukemia in the older patient.

Authors:  John E Godwin; Scott E Smith
Journal:  Crit Rev Oncol Hematol       Date:  2003-10-15       Impact factor: 6.312

5.  Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia.

Authors:  Bruce D Cheson; John M Bennett; Kenneth J Kopecky; Thomas Büchner; Cheryl L Willman; Elihu H Estey; Charles A Schiffer; Hartmut Doehner; Martin S Tallman; T Andrew Lister; Francesco Lo-Coco; Roel Willemze; Andrea Biondi; Wolfgang Hiddemann; Richard A Larson; Bob Löwenberg; Miguel A Sanz; David R Head; Ryuzo Ohno; Clara D Bloomfield; Francesco LoCocco
Journal:  J Clin Oncol       Date:  2003-12-15       Impact factor: 44.544

6.  FLT3 mutations in childhood acute lymphoblastic leukemia.

Authors:  Scott A Armstrong; Meghann E Mabon; Lewis B Silverman; Aihong Li; John G Gribben; Edward A Fox; Stephen E Sallan; Stanley J Korsmeyer
Journal:  Blood       Date:  2003-12-11       Impact factor: 22.113

7.  Clinical impact of internal tandem duplications and activating point mutations in FLT3 in acute myeloid leukemia in elderly patients.

Authors:  Anna Andersson; Bertil Johansson; Carin Lassen; Felix Mitelman; Rolf Billström; Thoas Fioretos
Journal:  Eur J Haematol       Date:  2004-05       Impact factor: 2.997

8.  Incidence and prognostic value of FLT3 internal tandem duplication and D835 mutations in acute myeloid leukemia.

Authors:  Isabel Moreno; Guillermo Martín; Pascual Bolufer; Eva Barragán; Eva Rueda; José Román; Pascual Fernández; Pilar León; Armando Mena; José Cervera; Antonio Torres; Miguel A Sanz
Journal:  Haematologica       Date:  2003-01       Impact factor: 9.941

9.  Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm.

Authors:  Stefan Fröhling; Richard F Schlenk; Jochen Breitruck; Axel Benner; Sylvia Kreitmeier; Karen Tobis; Hartmut Döhner; Konstanze Döhner
Journal:  Blood       Date:  2002-08-08       Impact factor: 22.113

10.  Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461).

Authors:  John C Byrd; Krzysztof Mrózek; Richard K Dodge; Andrew J Carroll; Colin G Edwards; Diane C Arthur; Mark J Pettenati; Shivanand R Patil; Kathleen W Rao; Michael S Watson; Prasad R K Koduru; Joseph O Moore; Richard M Stone; Robert J Mayer; Eric J Feldman; Frederick R Davey; Charles A Schiffer; Richard A Larson; Clara D Bloomfield
Journal:  Blood       Date:  2002-08-01       Impact factor: 22.113

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  4 in total

1.  TP53 mutations in older adults with acute myeloid leukemia.

Authors:  Masamitsu Yanada; Yukiya Yamamoto; Sachiko Iba; Akinao Okamoto; Yoko Inaguma; Masutaka Tokuda; Satoko Morishima; Tadaharu Kanie; Shuichi Mizuta; Yoshiki Akatsuka; Masataka Okamoto; Nobuhiko Emi
Journal:  Int J Hematol       Date:  2016-01-18       Impact factor: 2.490

Review 2.  Acute myeloid leukemia in older adults.

Authors:  Masamitsu Yanada; Tomoki Naoe
Journal:  Int J Hematol       Date:  2012-07-13       Impact factor: 2.490

Review 3.  DNMT3A R882 Mutations Predict a Poor Prognosis in AML: A Meta-Analysis From 4474 Patients.

Authors:  Xiao-Qing Yuan; Li Peng; Wen-Jing Zeng; Bin-Yuan Jiang; Guan-Cheng Li; Xiao-Ping Chen
Journal:  Medicine (Baltimore)       Date:  2016-05       Impact factor: 1.889

4.  Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Authors:  Xavier Poiré; Myriam Labopin; Emmanuelle Polge; Jakob Passweg; Charles Craddock; Didier Blaise; Jan J Cornelissen; Liisa Volin; Nigel H Russell; Gérard Socié; Mauricette Michallet; Nathalie Fegueux; Patrice Chevallier; Arne Brecht; Mathilde Hunault-Berger; Mohamad Mohty; Jordi Esteve; Arnon Nagler
Journal:  Haematologica       Date:  2017-12-14       Impact factor: 9.941

  4 in total

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