Literature DB >> 27774847

Differential response to hypomethylating agents based on sex: a report on behalf of the MDS Clinical Research Consortium (MDS CRC).

Amy E DeZern1, Amer M Zeidan2, John Barnard3, Wesley Hand1, Najla Al Ali4, Francis Brown5, Cassie Zimmerman3, Gail J Roboz6, Guillermo Garcia-Manero7, David P Steensma5, Rami S Komrokji4, Mikkael A Sekeres3.   

Abstract

First-line therapy for higher-risk myelodysplastic syndromes (MDS) includes decitabine (DAC) or azacitidine (AZA). Variables have not identified differential response rates between these. We assessed the influence of patient sex on outcomes including overall survival (OS) in 642 patients with higher-risk MDS treated with AZA or DAC. DAC-treated patients (35% of females, 31% of males) had marginally better OS than AZA-treated patients (p = .043), (median OS of 18.7 months versus 16.4 months), but the difference varied strongly by sex. Female patients treated with DAC had a longer median OS (21.1 months, 95% CI: 16.0-28.0) than female patients treated with AZA (13.2 months, 95% CI: 11.0-15.9; p = .0014), while for males there was no significant difference between HMAs (median OS 18.3 months with DAC versus 17.9 months for AZA, p = .59). The biological reason for this variability is unclear, but may be a consequence of differences in cytidine deaminase activity between men and women.

Entities:  

Keywords:  MDS; Sex; azacitidine; decitabine; hypomethylating agents

Mesh:

Substances:

Year:  2016        PMID: 27774847      PMCID: PMC5394924          DOI: 10.1080/10428194.2016.1246726

Source DB:  PubMed          Journal:  Leuk Lymphoma        ISSN: 1026-8022


  24 in total

1.  Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice.

Authors:  Jan H Beumer; Julie L Eiseman; Judith A Gilbert; Julianne L Holleran; Archibong E Yellow-Duke; Dana M Clausen; David Z D'Argenio; Matthew M Ames; Pamela A Hershberger; Robert A Parise; Lihua Bai; Joseph M Covey; Merrill J Egorin
Journal:  Cancer Chemother Pharmacol       Date:  2010-05-05       Impact factor: 3.333

2.  Cytidine deaminase and the development of resistance to arabinosyl cytosine.

Authors:  C D Steuart; P J Burke
Journal:  Nat New Biol       Date:  1971-09-22

3.  An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2'-deoxycytidine (decitabine) in 177 patients.

Authors:  P W Wijermans; M Lübbert; G Verhoef; V Klimek; A Bosly
Journal:  Ann Hematol       Date:  2005-12       Impact factor: 3.673

4.  Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-azacytidine and 5-aza-2'-deoxycytidine.

Authors:  F Creusot; G Acs; J K Christman
Journal:  J Biol Chem       Date:  1982-02-25       Impact factor: 5.157

5.  Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia.

Authors:  Bruce D Cheson; Peter L Greenberg; John M Bennett; Bob Lowenberg; Pierre W Wijermans; Stephen D Nimer; Antonio Pinto; Miloslav Beran; Theo M de Witte; Richard M Stone; Moshe Mittelman; Guillermo F Sanz; Steven D Gore; Charles A Schiffer; Hagop Kantarjian
Journal:  Blood       Date:  2006-04-11       Impact factor: 22.113

Review 6.  The myelodysplastic syndromes.

Authors:  Mikkael A Sekeres
Journal:  Expert Opin Biol Ther       Date:  2007-03       Impact factor: 4.388

7.  Impact of cytidine deaminase activity on intrinsic resistance to cytarabine in carcinoma cells.

Authors:  Takuya Ohta; Hiroki Hori; Masahiro Ogawa; Masazumi Miyahara; Hajime Kawasaki; Norihisa Taniguchi; Yoshihiro Komada
Journal:  Oncol Rep       Date:  2004-11       Impact factor: 3.906

8.  Prognostic impact of age and gender in 897 untreated patients with primary myelodysplastic syndromes.

Authors:  T Nösslinger; H Tüchler; U Germing; W R Sperr; O Krieger; D Haase; M Lübbert; R Stauder; A Giagounidis; P Valent; M Pfeilstöcker
Journal:  Ann Oncol       Date:  2009-07-15       Impact factor: 32.976

Review 9.  The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes.

Authors:  James W Vardiman; Jüergen Thiele; Daniel A Arber; Richard D Brunning; Michael J Borowitz; Anna Porwit; Nancy Lee Harris; Michelle M Le Beau; Eva Hellström-Lindberg; Ayalew Tefferi; Clara D Bloomfield
Journal:  Blood       Date:  2009-04-08       Impact factor: 22.113

10.  Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-tetrahydrouridine.

Authors:  Jan H Beumer; Julie L Eiseman; Robert A Parise; Erin Joseph; Joseph M Covey; Merrill J Egorin
Journal:  Clin Cancer Res       Date:  2008-06-01       Impact factor: 12.531

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  3 in total

1.  Gender disparity in the survival of patients with primary myelodysplastic syndrome.

Authors:  Fangfang Wang; Jun Ni; Lei Wu; Ying Wang; Bin He; Duonan Yu
Journal:  J Cancer       Date:  2019-01-30       Impact factor: 4.207

Review 2.  Sex-Related Differences in Chronic Myeloid Neoplasms: From the Clinical Observation to the Underlying Biology.

Authors:  Theodoros Karantanos; Tania Jain; Alison R Moliterno; Richard J Jones; Amy E DeZern
Journal:  Int J Mol Sci       Date:  2021-03-05       Impact factor: 5.923

3.  Decitabine- and 5-azacytidine resistance emerges from adaptive responses of the pyrimidine metabolism network.

Authors:  Xiaorong Gu; Rita Tohme; Benjamin Tomlinson; Nneha Sakre; Metis Hasipek; Lisa Durkin; Caroline Schuerger; Dale Grabowski; Asmaa M Zidan; Tomas Radivoyevitch; Changjin Hong; Hetty Carraway; Betty Hamilton; Ronald Sobecks; Bhumika Patel; Babal K Jha; Eric D Hsi; Jaroslaw Maciejewski; Yogen Saunthararajah
Journal:  Leukemia       Date:  2020-08-07       Impact factor: 12.883

  3 in total

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