青少年及年轻成人急性髓系白血病基因突变的预后价值
Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia.
作者信息
Kuwatsuka Yachiyo, Tomizawa Daisuke, Kihara Rika, Nagata Yasunobu, Shiba Norio, Iijima-Yamashita Yuka, Shimada Akira, Deguchi Takao, Miyachi Hayato, Tawa Akio, Taga Takashi, Kinoshita Akitoshi, Nakayama Hideki, Kiyokawa Nobutaka, Saito Akiko Moriya, Koh Katsuyoshi, Goto Hiroaki, Kosaka Yoshiyuki, Asou Norio, Ohtake Shigeki, Miyawaki Shuichi, Miyazaki Yasushi, Sakura Toru, Ozawa Yukiyasu, Usui Noriko, Kanamori Heiwa, Ito Yoshikazu, Imai Kiyotoshi, Suehiro Youko, Kobayashi Shinichi, Kitamura Kunio, Sakaida Emiko, Ogawa Seishi, Naoe Tomoki, Hayashi Yasuhide, Horibe Keizo, Manabe Atsushi, Mizutani Shuki, Adachi Souichi, Kiyoi Hitoshi
机构信息
Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
出版信息
Int J Hematol. 2018 Feb;107(2):201-210. doi: 10.1007/s12185-017-2340-z. Epub 2017 Oct 12.
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.
已知青少年及年轻成人（AYA）急性髓系白血病（AML）的临床结局和遗传背景与年幼儿童及老年成人不同。为阐明基因突变对AYA AML患者临床结局的影响，我们分析了日本儿科白血病研究组（JPLSG）AML - 05研究和日本成人白血病研究组（JALSG）AML20研究的数据。纳入了15 - 39岁的AYA患者（n = 103）。分析了FLT3 - ITD、KIT、CEBPA、NRAS、KRAS、WT1、MLL - PTD和NPM1基因突变情况。AYA患者3年总生存率（OS）为61%，无事件生存率为38%。多因素分析显示，FLT3 - ITD（HR 2.10；95% CI 1.07 - 4.12；p = 0.031）和NPM1（HR 0.24；95% CI 0.06 - 1.00；p = 0.050）突变与总死亡风险相关。根据FLT3 - ITD和NPM1突变状态，OS有显著差异（p = 0.03）。无FLT3 - ITD时NPM1突变患者生存率为100%，无NPM1突变时FLT3 - ITD患者生存率为35%（95% CI 14 - 57%）。AML - 05和AML20研究参与者中AYA患者、儿童（n = 413）及老年成人（n = 124）的OS有显著差异（p < 0.0001）。这是首份整合日本主要儿科和成人研究组AYA AML临床和遗传数据的报告。
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