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01-02-2018 | Original Article

Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia

Authors: Yachiyo Kuwatsuka, Daisuke Tomizawa, Rika Kihara, Yasunobu Nagata, Norio Shiba, Yuka Iijima-Yamashita, Akira Shimada, Takao Deguchi, Hayato Miyachi, Akio Tawa, Takashi Taga, Akitoshi Kinoshita, Hideki Nakayama, Nobutaka Kiyokawa, Akiko Moriya Saito, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Norio Asou, Shigeki Ohtake, Shuichi Miyawaki, Yasushi Miyazaki, Toru Sakura, Yukiyasu Ozawa, Noriko Usui, Heiwa Kanamori, Yoshikazu Ito, Kiyotoshi Imai, Youko Suehiro, Shinichi Kobayashi, Kunio Kitamura, Emiko Sakaida, Seishi Ogawa, Tomoki Naoe, Yasuhide Hayashi, Keizo Horibe, Atsushi Manabe, Shuki Mizutani, Souichi Adachi, Hitoshi Kiyoi

Published in: International Journal of Hematology | Issue 2/2018

Abstract

Clinical outcomes and the genetic background of acute myeloid leukemia (AML) in adolescent and young adults (AYAs) are known to differ in younger children and older adults. To clarify the impact of genetic mutations on clinical outcomes of AYAs with AML, we analyzed data from the JPLSG AML-05 and JALSG AML201 studies. AYAs aged 15–39 years (n = 103) were included. FLT3-ITD, KIT, CEBPA, NRAS, KRAS, WT1, MLL-PTD, and NPM1 mutations were analyzed. Overall survival (OS) of the AYAs was 61% and event-free survival was 38% at 3 years. FLT3-ITD (HR 2.10; 95% CI 1.07–4.12; p = 0.031) and NPM1 (HR 0.24; 95% CI 0.06–1.00; p = 0.050) mutations were associated with risk of overall mortality in multivariate analysis. OS was significantly different according to FLT3-ITD and NPM1 mutation status (p = 0.03). Survival was 100% with NPM1 mutations in the absence of FLT3-ITD and 35% (95% CI 14–57%) with FLT3-ITD in the absence of NPM1 mutations. The OS of AYAs, children (n = 413) and older adults (n = 124) of the AML-05 and AML201 participants were significantly different (p < 0.0001). This is the first report to combine clinical and genetic data of AYA AML from the major Japanese pediatric and adult study groups.

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Title: Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia
Authors: Yachiyo Kuwatsuka
Daisuke Tomizawa
Rika Kihara
Yasunobu Nagata
Norio Shiba
Yuka Iijima-Yamashita
Akira Shimada
Takao Deguchi
Hayato Miyachi
Akio Tawa
Takashi Taga
Akitoshi Kinoshita
Hideki Nakayama
Nobutaka Kiyokawa
Akiko Moriya Saito
Katsuyoshi Koh
Hiroaki Goto
Yoshiyuki Kosaka
Norio Asou
Shigeki Ohtake
Shuichi Miyawaki
Yasushi Miyazaki
Toru Sakura
Yukiyasu Ozawa
Noriko Usui
Heiwa Kanamori
Yoshikazu Ito
Kiyotoshi Imai
Youko Suehiro
Shinichi Kobayashi
Kunio Kitamura
Emiko Sakaida
Seishi Ogawa
Tomoki Naoe
Yasuhide Hayashi
Keizo Horibe
Atsushi Manabe
Shuki Mizutani
Souichi Adachi
Hitoshi Kiyoi
Publication date: 01-02-2018
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 2/2018
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-017-2340-z

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