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Postazacitidine clo...
Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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2023-03-29
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American Society of Hematology,2023
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:153413336
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http://kipublications.ki.se/Default.aspx?queryparsed=id:153413336URI
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https://doi.org/10.1182/bloodadvances.2022009564DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Azacitidine is a mainstay of therapy for 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 post-treatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms. They were analyzed for gene mutations in pre- (n=449) and post- (n=289) treatment bone marrow samples using targeted-capture sequencing to assess the impact of gene mutations and their post-treatment clone size on treatment outcomes. In Cox proportional hazard modeling, multi-hit TP53 mutation (HR, 2.03; 95% CI, 1.42-2.91; P<.001), EZH2 mutation (HR, 1.71; 95% CI, 1.14-2.54; P=.009), and DDX41 mutations (HR, 0.33; 95% CI, 0.17-0.62; P<.001), together with age, high-risk karyotypes, low platelet, and high blast counts, independently predicted OS. Post-treatment clone size accounting for all drivers significantly correlated with International Working Group (IWG)-response (P<.001, trend test), except for that of DDX41-mutated clones, which did not predict IWG-response. Combined, IWG-response and post-treatment clone size further improved the prediction of the original model and even that of a recently proposed molecular prediction model, IPSS-M (c-index, 0.653 vs 0.688; P<.001, likelihood ratio test). In conclusion, evaluation of post-treatment clone size, together with pre-treatment mutational profile as well as IWG-response have a role in better prognostication of azacitidine-treated myelodysplasia patients.
Added entries (persons, corporate bodies, meetings, titles ...)
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Tobiasson, MKarolinska Institutet
(author)
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Sato, S
(author)
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Bernard, E
(author)
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Ohtake, S
(author)
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Takeda, J
(author)
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Creignou, MKarolinska Institutet
(author)
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Zhao, LY
(author)
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Kusakabe, M
(author)
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Shibata, Y
(author)
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Nakamura, N
(author)
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Watanabe, M
(author)
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Hiramoto, N
(author)
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Shiozawa, Y
(author)
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Shiraishi, Y
(author)
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Tanaka, H
(author)
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Yoshida, K
(author)
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Kakiuchi, N
(author)
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Makishima, H
(author)
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Nakagawa, M
(author)
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Usuki, K
(author)
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Watanabe, M
(author)
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Imada, K
(author)
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Handa, H
(author)
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Taguchi, M
(author)
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Kiguchi, T
(author)
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Ohyashiki, K
(author)
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Ishikawa, T
(author)
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Takaori-Kondo, A
(author)
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Tsurumi, H
(author)
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Kasahara, S
(author)
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Chiba, S
(author)
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Naoe, T
(author)
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Miyano, S
(author)
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Papaemanuil, E
(author)
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Miyazaki, Y
(author)
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Hellstrom-Lindberg, EKarolinska Institutet
(author)
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Ogawa, S
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:Blood advances: American Society of Hematology7:14, s. 3624-36362473-95372473-9529
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- By the author/editor
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Nannya, Y
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Tobiasson, M
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Sato, S
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Bernard, E
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Ohtake, S
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Takeda, J
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show more...
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Creignou, M
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Zhao, LY
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Kusakabe, M
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Shibata, Y
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Nakamura, N
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Watanabe, M
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Hiramoto, N
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Shiozawa, Y
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Shiraishi, Y
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Tanaka, H
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Yoshida, K
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Kakiuchi, N
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Makishima, H
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Nakagawa, M
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Usuki, K
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Imada, K
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Handa, H
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Taguchi, M
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Kiguchi, T
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Ohyashiki, K
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Ishikawa, T
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Takaori-Kondo, A
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Tsurumi, H
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Kasahara, S
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Chiba, S
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Naoe, T
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Miyano, S
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Papaemanuil, E
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Miyazaki, Y
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Hellstrom-Lindbe ...
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Ogawa, S
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- Articles in the publication
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Blood advances
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Karolinska Institutet