Literature DB >> 19795507

Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities.

Farhad Ravandi1, Jean-Pierre Issa, Guillermo Garcia-Manero, Susan O'Brien, Sherry Pierce, Jianqin Shan, Gautam Borthakur, Srdan Verstovsek, Stefan Faderl, Jorge Cortes, Hagop Kantarjian.   

Abstract

BACKGROUND: Outcome of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) with chromosome 5 and 7 abnormalities (excluding del 5[q]) has been poor, with <10% of patients alive at 2 years.
METHODS: The authors investigated whether treatment with hypomethylating agents (5-azacytidine/decitabine) leads to an improved outcome. Between January 2004 and December 2007, 81 patients (37 [46%] with AML [>or=20% blasts]; 44 [54%] with high-risk MDS) with chromosome 5 and 7 abnormalities were treated with hypomethylating agents as their initial therapy. These included 68 patients with complex (>or=3) abnormalities and 13 with <3 aberrations. During the same period, 151 patients (126 with AML, 25 with MDS) with chromosome 5 and 7 abnormalities (128 complex, 23 noncomplex) were treated with intensive chemotherapy (including cytarabine-based regimens in 72% and other regimes in 28%).
RESULTS: The median ages for the 2 groups were 66 years and 61 years, respectively (ranges, 37-85 years and 19-89 years). Thirty-three (41%) patients in the hypomethylating group achieved complete remission (CR) versus 53 (35%) in the chemotherapy group (P=.395). With a median follow-up of 51 weeks (range, 12-101 weeks) and 40 weeks (range, 5-128 weeks), 22 of 33 patients in the hypomethylating group and 33 of 53 patients in the chemotherapy group had developed disease recurrence. The median CR duration was 45 weeks and 23 weeks, respectively (P=.153). The overall survival was superior for the hypomethylating group compared with the chemotherapy group (P=.019).
CONCLUSIONS: Treatment with hypomethylating agents may be superior to chemotherapy in patients with chromosome 5 and 7 abnormalities. Copyright (c) 2009 American Cancer Society.

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Year:  2009        PMID: 19795507      PMCID: PMC2794953          DOI: 10.1002/cncr.24661

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


  19 in total

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Journal:  Haematologica       Date:  2000-03       Impact factor: 9.941

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Journal:  Blood       Date:  1997-10-15       Impact factor: 22.113

4.  Effect of diagnosis (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia [AML]) on outcome of AML-type chemotherapy.

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Journal:  Blood       Date:  1997-10-15       Impact factor: 22.113

5.  Randomized phase II study of fludarabine + cytosine arabinoside + idarubicin +/- all-trans retinoic acid +/- granulocyte colony-stimulating factor in poor prognosis newly diagnosed acute myeloid leukemia and myelodysplastic syndrome.

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6.  Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B.

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7.  Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.

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8.  Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study.

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9.  The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties.

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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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  34 in total

1.  Decitabine in patients with newly diagnosed and relapsed acute myeloid leukemia.

Authors:  Ellen K Ritchie; Eric J Feldman; Paul J Christos; Sarah D Rohan; Catherine B Lagassa; Cindy Ippoliti; Joseph M Scandura; Karen Carlson; Gail J Roboz
Journal:  Leuk Lymphoma       Date:  2013-02-07

2.  Randomized phase IIb study of low-dose cytarabine and lintuzumab versus low-dose cytarabine and placebo in older adults with untreated acute myeloid leukemia.

Authors:  Mikkael A Sekeres; Jeffrey E Lancet; Brent L Wood; Laurie E Grove; Larissa Sandalic; Eric L Sievers; Joseph G Jurcic
Journal:  Haematologica       Date:  2012-07-16       Impact factor: 9.941

Review 3.  Following in the footsteps of acute myeloid leukemia: are we witnessing the start of a therapeutic revolution for higher-risk myelodysplastic syndromes?

Authors:  Jan Philipp Bewersdorf; Amer M Zeidan
Journal:  Leuk Lymphoma       Date:  2020-05-18

Review 4.  Decitabine: a review of its use in older patients with acute myeloid leukaemia.

Authors:  Monique P Curran
Journal:  Drugs Aging       Date:  2013-06       Impact factor: 3.923

Review 5.  Management of Relapsed/Refractory Acute Myeloid Leukemia in the Elderly: Current Strategies and Developments.

Authors:  Jeffrey C Bryan; Elias J Jabbour
Journal:  Drugs Aging       Date:  2015-08       Impact factor: 3.923

6.  An update on the safety and efficacy of decitabine in the treatment of myelodysplastic syndromes.

Authors:  Jacqueline S Garcia; Nitin Jain; Lucy A Godley
Journal:  Onco Targets Ther       Date:  2010-06-24       Impact factor: 4.147

7.  Challenges in treating older patients with acute myeloid leukemia.

Authors:  Lagadinou D Eleni; Zoumbos C Nicholas; Spyridonidis Alexandros
Journal:  J Oncol       Date:  2010-06-10       Impact factor: 4.375

8.  Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia.

Authors:  Alfonso Quintás-Cardama; Farhad Ravandi; Theresa Liu-Dumlao; Mark Brandt; Stefan Faderl; Sherry Pierce; Gautam Borthakur; Guillermo Garcia-Manero; Jorge Cortes; Hagop Kantarjian
Journal:  Blood       Date:  2012-10-15       Impact factor: 22.113

Review 9.  Clinical developments in epigenetic-directed therapies in acute myeloid leukemia.

Authors:  Darren Pan; Raajit Rampal; John Mascarenhas
Journal:  Blood Adv       Date:  2020-03-10

10.  Azacitidine in the management of patients with myelodysplastic syndromes.

Authors:  Cyrus Khan; Neeta Pathe; Salman Fazal; John Lister; James M Rossetti
Journal:  Ther Adv Hematol       Date:  2012-12
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