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ASXL1 mutations wit...
ASXL1 mutations with serum EPO levels predict poor response to darbepoetin alfa in lower-risk MDS: W-JHS MDS01 trial
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Morita, Y (author)
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Nannya, Y (author)
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Ichikawa, M (author)
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Hanamoto, H (author)
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Shibayama, H (author)
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Maeda, Y (author)
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Hata, T (author)
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Miyamoto, T (author)
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Kawabata, H (author)
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Takeuchi, K (author)
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Tanaka, H (author)
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Kishimoto, J (author)
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Miyano, S (author)
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Matsumura, I (author)
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Ogawa, S (author)
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Akashi, K (author)
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Kanakura, Y (author)
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Mitani, K (author)
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- 2022-07-12
- 2022
- English.
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In: International journal of hematology. - : Springer Science and Business Media LLC. - 1865-3774 .- 0925-5710. ; 116:5, s. 659-668
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https://doi.org/10.1...
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Abstract
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- Darbepoetin alfa (DA) is used to treat anemia in lower-risk (IPSS low or int-1) myelodysplastic syndromes (MDS). However, whether mutations can predict the effectiveness of DA has not been examined. The present study aimed to determine predictive gene mutations. The primary endpoint was a correlation between the presence of highly frequent (≥ 10%) mutations and hematological improvement-erythroid according to IWG criteria 2006 by DA (240 μg/week) until week 16. The study included 79 patients (age 29–90, median 77.0 years; 52 [65.8%] male). Frequently (≥ 10%) mutated genes were SF3B1 (24 cases, 30.4%), TET2 (20, 25.3%), SRSF2 (10, 12.7%), ASXL1 (9, 11.4%), and DNMT3A (8, 10.1%). Overall response rate to DA was 70.9%. Multivariable analysis including baseline erythropoietin levels and red blood cell transfusion volumes as variables revealed that erythropoietin levels and mutations of ASXL1 gene were significantly associated with worse response (odds ratio 0.146, 95% confidence interval 0.042–0.503; p = 0.0023, odds ratio 0.175, 95% confidence interval 0.033–0.928; p = 0.0406, respectively). This study indicated that anemic patients who have higher erythropoietin levels and harbor ASXL1 gene mutations may respond poorly to DA. Alternative strategies are needed for the treatment of anemia in this population. Trial registration number and date of registration: UMIN000022185 and 09/05/2016.
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- By the author/editor
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Morita, Y
-
Nannya, Y
-
Ichikawa, M
-
Hanamoto, H
-
Shibayama, H
-
Maeda, Y
-
show more...
-
Hata, T
-
Miyamoto, T
-
Kawabata, H
-
Takeuchi, K
-
Tanaka, H
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Kishimoto, J
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Miyano, S
-
Matsumura, I
-
Ogawa, S
-
Akashi, K
-
Kanakura, Y
-
Mitani, K
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show less...
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International jo ...
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Karolinska Institutet