Literature DB >> 21324374

Role of allogeneic transplantation for FLT3/ITD acute myeloid leukemia: outcomes from 133 consecutive newly diagnosed patients from a single institution.

Amy E DeZern1, Anthony Sung, Sharon Kim, B Douglas Smith, Judith E Karp, Steven D Gore, Richard J Jones, Ephraim Fuchs, Leo Luznik, Michael McDevitt, Mark Levis.   

Abstract

Acute myelogenous leukemia (AML) patients with FLT3/ITD mutations have an inferior survival compared to AML patients with wild-type (WT) FLT3, primarily because of an increased relapse rate. Allogeneic transplantation represents a postremission therapy that is effective at reducing the risk of relapse for many cases of poor-risk AML. Whether or not allogeneic transplantation in first complete remission (CR) can improve outcomes for patients with FLT3/ITD AML remains controversial. Our institution has adopted a policy of pursuing allogeneic transplantation, including the use of alternate donors, for FLT3/ITD AML patients in remission. As part of an instituional review board-approved study, we performed a review of the clinical data from November 1, 2004, to October 31, 2008, on all adult patients under the age of 60 presenting in consecutive fashion to the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins with newly diagnosed non-M3 AML. We followed their outcomes through August 1, 2010. During the study period, 133 previously untreated AML patients between the ages of 20 and 59 were diagnosed and received induction and consolidation therapy at our institution. Of these 133 patients, 31 (23%) harbored an FLT3/ITD mutation at diagnosis. The median overall survival (OS) from the time of diagnosis for the FLT3/ITD AML patients was compared to the OS of the entire cohort and found to be comparable (19.3 months versus 15.5 months, P = .56). Historically, OS for FLT3/ITD AML patients is significantly worse than for AML patients lacking this mutation. However, the OS for the 31 FLT3/ITD patients reported here was comparable to the 102 patients with WT FLT3 over the same 4-year time period. One difference that might have contributed to the surprising outcomes for the FLT3/ITD group is our aggressive pursuit of allogeneic bone marrow transplant (BMT) in CR1 within this group (60% of FLT3/ITD versus 17% with WT). Our single-institution study of consecutively treated AML patients supports the hypothesis that allogeneic transplant in early CR1 improves the long-term outcomes for FLT3/ITD AML.
Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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Year:  2011        PMID: 21324374      PMCID: PMC3110512          DOI: 10.1016/j.bbmt.2011.02.003

Source DB:  PubMed          Journal:  Biol Blood Marrow Transplant        ISSN: 1083-8791            Impact factor:   5.742


  25 in total

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6.  Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia.

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7.  Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study.

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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).

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Journal:  Blood       Date:  2002-08-01       Impact factor: 22.113

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  48 in total

1.  Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission.

Authors:  Andrew M Brunner; Shuli Li; Amir T Fathi; Martha Wadleigh; Vincent T Ho; Kerry Collier; Christine Connolly; Karen K Ballen; Corey S Cutler; Bimalangshu R Dey; Areej El-Jawahri; Sarah Nikiforow; Steven L McAfee; John Koreth; Daniel J Deangelo; Edwin P Alyea; Joseph H Antin; Thomas R Spitzer; Richard M Stone; Robert J Soiffer; Yi-Bin Chen
Journal:  Br J Haematol       Date:  2016-07-19       Impact factor: 6.998

Review 2.  FLT3 inhibitors in AML: are we there yet?

Authors:  Akshay Sudhindra; Catherine Choy Smith
Journal:  Curr Hematol Malig Rep       Date:  2014-06       Impact factor: 3.952

3.  Allogeneic Transplantation in First Remission Improves Outcomes Irrespective of FLT3-ITD Allelic Ratio in FLT3-ITD-Positive Acute Myelogenous Leukemia.

Authors:  Betül Oran; Jorge Cortes; Amer Beitinjaneh; Hsiang-Chun Chen; Marcos de Lima; Keyur Patel; Farhad Ravandi; Xuemei Wang; Mark Brandt; Borje S Andersson; Stefan Ciurea; Fabio P Santos; Leandro de Padua Silva; Elizabeth J Shpall; Richard E Champlin; Hagop Kantarjian; Gautam Borthakur
Journal:  Biol Blood Marrow Transplant       Date:  2016-04-04       Impact factor: 5.742

Review 4.  The Future of Targeting FLT3 Activation in AML.

Authors:  Mark B Leick; Mark J Levis
Journal:  Curr Hematol Malig Rep       Date:  2017-06       Impact factor: 3.952

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

Authors:  Talha Badar; Hagop M Kantarjian; Graciela M Nogueras-Gonzalez; Gautam Borthakur; Guillermo Garcia Manero; Michael Andreeff; Marina Konopleva; Tapan M Kadia; Naval Daver; William G Wierda; Raja Luthra; Keyur Patel; Betul Oran; Richard Champlin; Farhad Ravandi; Jorge E Cortes
Journal:  Am J Hematol       Date:  2015-09-10       Impact factor: 10.047

Review 6.  Will FLT3 inhibitors fulfill their promise in acute meyloid leukemia?

Authors:  Keith W Pratz; Selina M Luger
Journal:  Curr Opin Hematol       Date:  2014-03       Impact factor: 3.284

7.  Pre-transplant MRD predicts outcome following reduced-intensity and myeloablative allogeneic hemopoietic SCT in AML.

Authors:  C Anthias; F L Dignan; R Morilla; A Morilla; M E Ethell; M N Potter; B E Shaw
Journal:  Bone Marrow Transplant       Date:  2014-02-10       Impact factor: 5.483

8.  Umbilical cord blood transplantation is a suitable option for consolidation of acute myeloid leukemia with FLT3-ITD.

Authors:  Craig E Eckfeldt; Nicole Randall; Ryan M Shanley; Sophia Yohe; Nelli Bejanyan; Michelle Dolan; Erica D Warlick; Michael R Verneris; Claudio G Brunstein; John E Wagner; Daniel J Weisdorf; Celalettin Ustun
Journal:  Haematologica       Date:  2016-04-28       Impact factor: 9.941

Review 9.  Timed sequential therapy for acute myelogenous leukemia: Results of a retrospective study of 301 patients and review of the literature.

Authors:  Kelly J Norsworthy; Amy E DeZern; Hua-Ling Tsai; Wesley A Hand; Ravi Varadhan; Steven D Gore; Ivana Gojo; Keith Pratz; Hetty E Carraway; Margaret Showel; Michael A McDevitt; Douglas Gladstone; Gabriel Ghiaur; Gabrielle Prince; Amy H Seung; Dina Benani; Mark J Levis; Judith E Karp; B Douglas Smith
Journal:  Leuk Res       Date:  2017-08-30       Impact factor: 3.156

Review 10.  FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance.

Authors:  Michael R Grunwald; Mark J Levis
Journal:  Int J Hematol       Date:  2013-04-24       Impact factor: 2.490

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