Literature DB >> 26299958

Improvement in clinical outcome of FLT3 ITD mutated acute myeloid leukemia patients over the last one and a half decade.

Talha Badar1, Hagop M Kantarjian1, Graciela M Nogueras-Gonzalez, Gautam Borthakur1, Guillermo Garcia Manero1, Michael Andreeff1, Marina Konopleva2, Tapan M Kadia1, Naval Daver1, William G Wierda1, Raja Luthra2, Keyur Patel2, Betul Oran3, Richard Champlin3, Farhad Ravandi1, Jorge E Cortes1.   

Abstract

AML with FLT3 ITD mutations are associated with poor outcome. We reviewed outcomes of patients with FLT3 ITD mutated AML to investigate trends over time. We analyzed 224 AML patients (excluding patients with core binding factor and acute promyelocytic leukemia) referred to our institution between 2000 and 2014. Patients were divided into five cohorts by era: 2000-2002 (Era 1, n = 19), 2003-2005 (Era 2, n = 41), 2006-2008 (Era 3, n = 53), 2009-2011 (Era 4, n = 55), and 2012-2014 (Era 5, n = 56) to analyze differences in outcome. The baseline characteristics were not statistically different across Eras. The response rate (CR/CRp) from Era 1-5 was 68%, 49%, 72%, 73%, and 75%, respectively. The overall response rate (all Eras) with chemotherapy alone versus chemotherapy plus FLT3 inhibitor was 67% and 72.5%, respectively (P = 0.4). The median time to relapse was 6, 3.6, 7.9, 8.1 months and not reached from Eras 1 through 5, respectively (P = 0.001). The median OS has improved: 9.6, 7.6, 14.4, 15.7, and 17.8 month from Eras 1-5, respectively (P = <0.001). Stem cell transplant as a time-dependent variable, showed better OS in the univariate analysis (HR: 0.57, 95% CI: 0.39-0.84, P = 0.004) but did not retained its significance in multivariate analysis (HR: 0.75, 95% CI: 0.50-1.13, P = 0.16). Our data suggest improvement in outcome of FLT3 ITD mutated AML patients over the last 15 years. This is probably due to improvement in treatment strategies, including but not limited to integration of FLT3 inhibitors and increased use of SCT.
© 2015 Wiley Periodicals, Inc.

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Year:  2015        PMID: 26299958      PMCID: PMC4618182          DOI: 10.1002/ajh.24140

Source DB:  PubMed          Journal:  Am J Hematol        ISSN: 0361-8609            Impact factor:   10.047


  37 in total

1.  Improved outcome after stem-cell transplantation in FLT3/ITD-positive AML.

Authors:  Martin Bornhäuser; Thomas Illmer; Markus Schaich; Silke Soucek; Gerhard Ehninger; Christian Thiede
Journal:  Blood       Date:  2007-03-01       Impact factor: 22.113

2.  Activating FLT3 mutations are detectable in chronic and blast phase of chronic myeloproliferative disorders other than chronic myeloid leukemia.

Authors:  Pei Lin; Dan Jones; L Jeffrey Medeiros; Weina Chen; Francisco Vega-Vazquez; Rajyalakshmi Luthra
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Journal:  Cancer Res       Date:  2007-01-15       Impact factor: 12.701

6.  FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications.

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Journal:  Blood       Date:  2004-05-04       Impact factor: 22.113

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Journal:  Blood       Date:  2002-08-08       Impact factor: 22.113

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  8 in total

Review 1.  Current Approaches to Transplantation for FLT3-ITD AML.

Authors:  Bradley D Hunter; Yi-Bin Chen
Journal:  Curr Hematol Malig Rep       Date:  2020-02       Impact factor: 3.952

2.  Outcome of FLT3-ITD-positive acute myeloid leukemia: impact of allogeneic stem cell transplantation and tyrosine kinase inhibitor treatment.

Authors:  Maximilian Fleischmann; Ulf Schnetzke; Karin G Schrenk; Volker Schmidt; Herbert G Sayer; Inken Hilgendorf; Andreas Hochhaus; Sebastian Scholl
Journal:  J Cancer Res Clin Oncol       Date:  2016-10-24       Impact factor: 4.553

Review 3.  Acute myeloid leukemia in the elderly: therapeutic options and choice.

Authors:  Jonathan A Webster; Keith W Pratz
Journal:  Leuk Lymphoma       Date:  2017-06-02

Review 4.  Treatment of Acute Myeloid Leukemia with the FLT3 Gene Mutation.

Authors:  Carlos Best-Aguilera; O Rodrigo Gómez-Vázquez; A Elizabeth Guzmán-Hernández; R Monserrat Rojas-Sotelo
Journal:  Curr Oncol Rep       Date:  2017-03       Impact factor: 5.075

5.  The sorafenib anti-relapse effect after alloHSCT is associated with heightened alloreactivity and accumulation of CD8+PD-1+ (CD279+) lymphocytes in marrow.

Authors:  Andrzej Lange; Emilia Jaskula; Janusz Lange; Grzegorz Dworacki; Dorota Nowak; Aleksandra Simiczyjew; Monika Mordak-Domagala; Mariola Sedzimirska
Journal:  PLoS One       Date:  2018-01-05       Impact factor: 3.240

Review 6.  Emerging treatment paradigms with FLT3 inhibitors in acute myeloid leukemia.

Authors:  Nicholas J Short; Hagop Kantarjian; Farhad Ravandi; Naval Daver
Journal:  Ther Adv Hematol       Date:  2019-02-15

Review 7.  Targeting FLT3 mutations in AML: review of current knowledge and evidence.

Authors:  Naval Daver; Richard F Schlenk; Nigel H Russell; Mark J Levis
Journal:  Leukemia       Date:  2019-01-16       Impact factor: 11.528

8.  Outcomes of pediatric acute myeloid leukemia patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era.

Authors:  Sujin Choi; Bo Kyung Kim; Hong Yul Ahn; Kyung Taek Hong; Jung Yoon Choi; Hee Young Shin; Hyoung Jin Kang
Journal:  Blood Res       Date:  2020-12-31
  8 in total

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