Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
25 07 2023
25 07 2023
Historique:
accepted:
12
01
2023
received:
19
12
2022
medline:
19
7
2023
pubmed:
30
3
2023
entrez:
29
3
2023
Statut:
ppublish
Résumé
Azacitidine is a mainstay of therapy for myelodysplastic syndrome (MDS)-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their posttreatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms. They were analyzed for gene mutations in pretreatment (n = 449) and posttreatment (n = 289) bone marrow samples using targeted-capture sequencing to assess the impact of gene mutations and their posttreatment clone size on treatment outcomes. In Cox proportional hazard modeling, multihit TP53 mutation (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.42-2.91; P < .001), EZH2 mutation (HR, 1.71; 95% CI, 1.14-2.54; P = .009), and DDX41 mutation (HR, 0.33; 95% CI, 0.17-0.62; P < .001), together with age, high-risk karyotypes, low platelets, and high blast counts, independently predicted OS. Posttreatment clone size accounting for all drivers significantly correlated with International Working Group (IWG) response (P < .001, using trend test), except for that of DDX41-mutated clones, which did not predict IWG response. Combined, IWG response and posttreatment clone size further improved the prediction of the original model and even that of a recently proposed molecular prediction model, the molecular International Prognostic Scoring System (IPSS-M; c-index, 0.653 vs 0.688; P < .001, using likelihood ratio test). In conclusion, evaluation of posttreatment clone size, together with the pretreatment mutational profile as well as the IWG response play a role in better prognostication of azacitidine-treated patients with myelodysplasia.
Identifiants
pubmed: 36989067
pii: 495133
doi: 10.1182/bloodadvances.2022009564
pmc: PMC10365941
doi:
Substances chimiques
Azacitidine
M801H13NRU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3624-3636Informations de copyright
© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
Références
J Cancer Res Clin Oncol. 2019 Nov;145(11):2835-2843
pubmed: 31506740
N Engl J Med. 2016 Nov 24;375(21):2023-2036
pubmed: 27959731
Blood. 2002 Oct 15;100(8):2957-64
pubmed: 12351408
Oncotarget. 2016 Apr 19;7(16):22103-15
pubmed: 26959885
Eur J Haematol. 2020 May;104(5):488-498
pubmed: 31990086
Lancet Oncol. 2009 Mar;10(3):223-32
pubmed: 19230772
Ann Hematol. 2013 Mar;92(3):411-2
pubmed: 23007277
Blood. 2016 Sep 1;128(9):1246-59
pubmed: 27268087
J Clin Oncol. 2002 May 15;20(10):2429-40
pubmed: 12011120
Ann Hematol. 2013 Jan;92(1):19-24
pubmed: 22948274
J Clin Oncol. 2021 Nov 20;39(33):3737-3746
pubmed: 34406850
Leuk Res. 2014 Jul;38(7):751-5
pubmed: 24836762
Nat Commun. 2017 Apr 21;8:15099
pubmed: 28429724
Leuk Lymphoma. 2012 May;53(5):760-2
pubmed: 22191378
N Engl J Med. 2014 Dec 25;371(26):2477-87
pubmed: 25426838
Oncotarget. 2017 Oct 27;8(63):106948-106961
pubmed: 29291002
Cell Rep. 2017 Jul 18;20(3):572-585
pubmed: 28723562
Leuk Lymphoma. 2014 Aug;55(8):1925-9
pubmed: 24138309
Am J Transl Res. 2019 Jun 15;11(6):3651-3658
pubmed: 31312376
Int J Hematol. 2022 Aug;116(2):228-238
pubmed: 35508695
Leukemia. 2011 Jul;25(7):1147-52
pubmed: 21494260
Blood. 2014 Oct 23;124(17):2705-12
pubmed: 25224413
N Engl J Med. 2017 Feb 9;376(6):536-547
pubmed: 28177873
Leukemia. 2011 Dec;25(12):1910-3
pubmed: 21760590
Leukemia. 2017 Apr;31(4):872-881
pubmed: 27740633
J Clin Oncol. 2014 Sep 1;32(25):2691-8
pubmed: 25092778
Nat Commun. 2016 Feb 24;7:10767
pubmed: 26908133
Blood. 2019 Mar 7;133(10):1020-1030
pubmed: 30404811
Leukemia. 2014 Jun;28(6):1280-8
pubmed: 24270737
Blood. 2011 Jan 13;117(2):403-11
pubmed: 20940414
Ann Hematol. 2017 Apr;96(4):559-565
pubmed: 28058491
J Clin Oncol. 2021 Apr 10;39(11):1223-1233
pubmed: 33539200
Leukemia. 2016 Jun;30(6):1416-8
pubmed: 26582646
Blood. 2009 Sep 24;114(13):2764-73
pubmed: 19546476
Leukemia. 2018 Dec;32(12):2546-2557
pubmed: 30275526
Ann Hematol. 2019 Nov;98(11):2523-2531
pubmed: 31637485
Leukemia. 2019 Mar;33(3):785-790
pubmed: 30291338
N Engl J Med. 2012 Mar 22;366(12):1090-8
pubmed: 22417201
Blood. 2017 Apr 27;129(17):2347-2358
pubmed: 28223278
Blood. 2023 Feb 2;141(5):534-549
pubmed: 36322930
Oncotarget. 2016 Aug 23;7(34):55264-55275
pubmed: 27419369
Hematology. 2016 Jan;21(1):34-41
pubmed: 26218077
Genes Chromosomes Cancer. 2011 Jul;50(7):527-34
pubmed: 21484930
Blood. 2006 Jul 15;108(2):419-25
pubmed: 16609072
Oncotarget. 2018 Jun 12;9(45):27882-27894
pubmed: 29963245
Ann Hematol. 2020 Mar;99(3):527-537
pubmed: 31989250
Nat Med. 2014 Dec;20(12):1472-8
pubmed: 25326804
Nature. 2019 Jan;565(7739):312-317
pubmed: 30602793
Leukemia. 2014 Jan;28(1):78-87
pubmed: 24045501
Ann Hematol. 2018 Nov;97(11):2025-2038
pubmed: 30084010
EBioMedicine. 2018 May;31:174-181
pubmed: 29728305
Leukemia. 2018 Jul;32(7):1598-1608
pubmed: 29472724
Leukemia. 2016 Mar;30(3):666-73
pubmed: 26514544
Haematologica. 2017 Jun;102(6):e216-e218
pubmed: 28209655
N Engl J Med. 2014 Dec 25;371(26):2488-98
pubmed: 25426837
Nat Med. 2020 Oct;26(10):1549-1556
pubmed: 32747829
Oncotarget. 2016 Mar 22;7(12):14172-87
pubmed: 26871476
Blood Adv. 2020 Feb 11;4(3):482-495
pubmed: 32027746
Genes Dev. 2005 May 15;19(10):1162-74
pubmed: 15870257
N Engl J Med. 2017 Feb 23;376(8):797-8
pubmed: 28225682