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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 languageEnglish
Pages (from-to)201-210
Number of pages10
JournalInternational journal of hematology
Volume107
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Keywords

  • AML
  • AYA
  • Genetic mutation
  • Prognosis

ASJC Scopus subject areas

  • Hematology

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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