Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements.
Adolescent
Adult
Aged
Aged, 80 and over
Female
Gene Rearrangement
Hematopoietic Stem Cell Transplantation
Histone-Lysine N-Methyltransferase
/ genetics
Humans
Leukemia, Myeloid, Acute
/ diagnosis
Male
Middle Aged
Mutation
Myeloid-Lymphoid Leukemia Protein
/ genetics
Prognosis
Retrospective Studies
Survival Analysis
Transplantation, Homologous
Young Adult
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
29 09 2021
29 09 2021
Historique:
received:
02
07
2021
accepted:
08
09
2021
revised:
03
09
2021
entrez:
30
9
2021
pubmed:
1
10
2021
medline:
5
2
2022
Statut:
epublish
Résumé
Acute myeloid leukemia (AML) with rearrangement of the lysine methyltransferase 2a gene (KMT2Ar) has adverse outcomes. However, reports on the prognostic impact of various translocations causing KMT2Ar are conflicting. Less is known about associated mutations and their prognostic impact. In a retrospective analysis, we identified 172 adult patients with KMT2Ar AML and compared them to 522 age-matched patients with diploid AML. KMT2Ar AML had fewer mutations, most commonly affecting RAS and FLT3 without significant impact on prognosis, except for patients with ≥2 mutations with lower overall survival (OS). KMT2Ar AML had worse outcomes compared with diploid AML when newly diagnosed and at relapse, especially following second salvage (median OS of 2.4 vs 4.8 months, P < 0.0001). Therapy-related KMT2Ar AML (t-AML) had worse outcomes compared with de novo KMT2Ar AML (median OS of 0.7 years vs 1.4 years, P < 0.0001). Allogeneic hematopoietic stem cell transplant (allo-HSCT) in first remission was associated with improved OS (5-year, 52 vs 14% for no allo-HSCT, P < 0.0001). In a multivariate analysis, translocation subtypes causing KMT2Ar did not predict survival, unlike age and allo-HSCT. In conclusion, KMT2Ar was associated with adverse outcomes regardless of translocation subtype. Therefore, AML risk stratification guidelines should include all KMT2Ar as adverse.
Identifiants
pubmed: 34588432
doi: 10.1038/s41408-021-00557-6
pii: 10.1038/s41408-021-00557-6
pmc: PMC8481264
doi:
Substances chimiques
KMT2A protein, human
0
Myeloid-Lymphoid Leukemia Protein
149025-06-9
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
162Subventions
Organisme : NCI NIH HHS
ID : K12 CA088084
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
J Clin Oncol. 2002 Aug 1;20(15):3254-61
pubmed: 12149299
Clin Lab Med. 2017 Dec;37(4):787-802
pubmed: 29128069
Haematologica. 2011 Jul;96(7):972-9
pubmed: 21459795
J Clin Oncol. 2021 Aug 10;39(23):2535-2538
pubmed: 34043455
Blood. 1997 Dec 1;90(11):4532-8
pubmed: 9373264
Leukemia. 2021 Sep;35(9):2482-2495
pubmed: 34131281
Leukemia. 2013 Apr;27(4):836-42
pubmed: 23135353
Blood. 2003 Oct 1;102(7):2395-402
pubmed: 12805060
Leukemia. 1998 Mar;12(3):317-25
pubmed: 9529125
J Natl Compr Canc Netw. 2021 Jan 06;19(1):16-27
pubmed: 33406488
Blood. 2015 Jul 2;126(1):9-16
pubmed: 25931582
Am J Hematol. 2017 Sep;92(9):924-928
pubmed: 28556489
Haematologica. 2014 Mar;99(3):465-73
pubmed: 24142997
Mol Cancer Res. 2018 Feb;16(2):279-285
pubmed: 29133595
Blood. 1993 Dec 15;82(12):3705-11
pubmed: 8260707
J Clin Oncol. 2014 Sep 20;32(27):3021-32
pubmed: 25092781
Nat Rev Cancer. 2007 Nov;7(11):823-33
pubmed: 17957188
N Engl J Med. 2014 Dec 25;371(26):2477-87
pubmed: 25426838
Nat Commun. 2018 May 2;9(1):1770
pubmed: 29720585
Leukemia. 2013 Sep;27(9):1933-6
pubmed: 23535558
Proc Natl Acad Sci U S A. 2020 Oct 20;117(42):26340-26346
pubmed: 33020282
N Engl J Med. 2012 Mar 22;366(12):1079-89
pubmed: 22417203
Leuk Res. 2020 Nov;98:106453
pubmed: 33059120
Leukemia. 1999 Dec;13(12):2107-13
pubmed: 10602437
Blood. 2006 Jul 15;108(2):441-51
pubmed: 16556894
Nat Genet. 2015 Sep;47(9):1030-7
pubmed: 26237430
Nat Genet. 2015 Apr;47(4):330-7
pubmed: 25730765
N Engl J Med. 2013 May 30;368(22):2059-74
pubmed: 23634996
N Engl J Med. 2016 Jun 9;374(23):2209-2221
pubmed: 27276561
J Clin Oncol. 2003 Dec 15;21(24):4642-9
pubmed: 14673054
Blood. 2002 Dec 15;100(13):4325-36
pubmed: 12393746
J Clin Oncol. 2009 Jun 20;27(18):3000-6
pubmed: 19380453
Leukemia. 2018 Feb;32(2):273-284
pubmed: 28701730
Blood. 2010 Jul 22;116(3):354-65
pubmed: 20385793
Blood. 2017 Apr 20;129(16):2217-2223
pubmed: 28179274
N Engl J Med. 2021 Mar 11;384(10):924-935
pubmed: 33704937
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Am J Epidemiol. 2010 Nov 1;172(9):1092-7
pubmed: 20802241
Blood. 2003 Sep 15;102(6):2198-204
pubmed: 12791658
N Engl J Med. 2014 Dec 25;371(26):2488-98
pubmed: 25426837
Am J Clin Pathol. 2004 Aug;122(2):298-306
pubmed: 15323147