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

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

doi:10.1007/s12185-017-2340-z

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

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 OhtakeShuichi 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

University Hospital

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	201-210
Number of pages	10
Journal	International journal of hematology
Volume	107
Issue number	2
DOIs	https://doi.org/10.1007/s12185-017-2340-z
Publication status	Published - Feb 1 2018

Keywords

AML
AYA
Genetic mutation
Prognosis

ASJC Scopus subject areas

Hematology

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10.1007/s12185-017-2340-z

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Kuwatsuka, Y., Tomizawa, D., Kihara, R., Nagata, Y., Shiba, N., Iijima-Yamashita, Y., Shimada, A., Deguchi, T., Miyachi, H., Tawa, A., Taga, T., Kinoshita, A., Nakayama, H., Kiyokawa, N., Saito, A. M., Koh, K., Goto, H., Kosaka, Y., Asou, N., ... Kiyoi, H. (2018). Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia. International journal of hematology, 107(2), 201-210. https://doi.org/10.1007/s12185-017-2340-z

Kuwatsuka, Y, Tomizawa, D, Kihara, R, Nagata, Y, Shiba, N, Iijima-Yamashita, Y, Shimada, A, Deguchi, T, Miyachi, H, Tawa, A, Taga, T, Kinoshita, A, Nakayama, H, Kiyokawa, N, Saito, AM, Koh, K, Goto, H, Kosaka, Y, Asou, N, Ohtake, S, Miyawaki, S, Miyazaki, Y, Sakura, T, Ozawa, Y, Usui, N, Kanamori, H, Ito, Y, Imai, K, Suehiro, Y, Kobayashi, S, Kitamura, K, Sakaida, E, Ogawa, S, Naoe, T, Hayashi, Y, Horibe, K, Manabe, A, Mizutani, S, Adachi, S & Kiyoi, H 2018, 'Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia', International journal of hematology, vol. 107, no. 2, pp. 201-210. https://doi.org/10.1007/s12185-017-2340-z

@article{d8b4c98869a648998000b737d68a7336,

title = "Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia",

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.",

keywords = "AML, AYA, Genetic mutation, Prognosis",

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

note = "Funding Information: The authors thank all the investigators and members of participating hospitals in AML studies conducted by the JALSG and the JPLSG. This work was supported in part by a grant for Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (AMED), and by the National Cancer Center Research and Development Fund (26-A-24). Dr. Miyachi reports grant from AMED and personal fees for consulting from BML. Inc. Dr. Saito reports grants from Ministry of Health, Labor and Welfare, grants from AMED, during the conduct of the study. Dr. Asou reports grants from Nippon Shinyaku Co., Ltd., grants and personal fees from Kyowa Hakko Kirin Co., Ltd., grants and personal fees from Chugai Pharmaceutical Co., Ltd. Publisher Copyright: {\textcopyright} 2017, The Japanese Society of Hematology.",

year = "2018",

month = feb,

day = "1",

doi = "10.1007/s12185-017-2340-z",

language = "English",

volume = "107",

pages = "201--210",

journal = "International Journal of Hematology",

issn = "0925-5710",

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TY - JOUR

T1 - Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia

AU - Kuwatsuka, Yachiyo

AU - Tomizawa, Daisuke

AU - Kihara, Rika

AU - Nagata, Yasunobu

AU - Shiba, Norio

AU - Iijima-Yamashita, Yuka

AU - Shimada, Akira

AU - Deguchi, Takao

AU - Miyachi, Hayato

AU - Tawa, Akio

AU - Taga, Takashi

AU - Kinoshita, Akitoshi

AU - Nakayama, Hideki

AU - Kiyokawa, Nobutaka

AU - Saito, Akiko Moriya

AU - Koh, Katsuyoshi

AU - Goto, Hiroaki

AU - Kosaka, Yoshiyuki

AU - Asou, Norio

AU - Ohtake, Shigeki

AU - Miyawaki, Shuichi

AU - Miyazaki, Yasushi

AU - Sakura, Toru

AU - Ozawa, Yukiyasu

AU - Usui, Noriko

AU - Kanamori, Heiwa

AU - Ito, Yoshikazu

AU - Imai, Kiyotoshi

AU - Suehiro, Youko

AU - Kobayashi, Shinichi

AU - Kitamura, Kunio

AU - Sakaida, Emiko

AU - Ogawa, Seishi

AU - Naoe, Tomoki

AU - Hayashi, Yasuhide

AU - Horibe, Keizo

AU - Manabe, Atsushi

AU - Mizutani, Shuki

AU - Adachi, Souichi

AU - Kiyoi, Hitoshi

N1 - Funding Information: The authors thank all the investigators and members of participating hospitals in AML studies conducted by the JALSG and the JPLSG. This work was supported in part by a grant for Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (AMED), and by the National Cancer Center Research and Development Fund (26-A-24). Dr. Miyachi reports grant from AMED and personal fees for consulting from BML. Inc. Dr. Saito reports grants from Ministry of Health, Labor and Welfare, grants from AMED, during the conduct of the study. Dr. Asou reports grants from Nippon Shinyaku Co., Ltd., grants and personal fees from Kyowa Hakko Kirin Co., Ltd., grants and personal fees from Chugai Pharmaceutical Co., Ltd. Publisher Copyright: © 2017, The Japanese Society of Hematology.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - AML

KW - AYA

KW - Genetic mutation

KW - Prognosis

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AN - SCOPUS:85031423150

SN - 0925-5710

VL - 107

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JO - International Journal of Hematology

JF - International Journal of Hematology

IS - 2

ER -

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

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