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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Acknowledgements
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).
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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., grants from Astellas Pharma Inc., grants and personal fees from Sumitomo Dainippon Pharma Co., Ltd., grants from Toyama Chemical Co., Ltd., grants and personal fees from Asahi Kasei Pharma Co., Ltd., personal fees from Boehringer Ingelheim Japan Inc., personal fees from Bristol-Myers Squibb Co., Ltd., personal fees from Nippon Kayaku Co., Ltd., personal fees from Yakult Honsha Co., Ltd., outside the submitted work. Dr. Miyazaki reports grants from AMED, grants from National Cancer Center Research and Development Fund, during the conduct of the study; grants and personal fees from Chugai Pharma, grants and personal fees from Kyowa Hakko Kirin Co., Ltd., grants and personal fees from Astellas Pharma, personal fees from Dainippon Sumitomo, personal fees from Celgene Japan, grants and personal fees from Novartis Japan, outside the submitted work. Dr. Usui reports grants from AMED, during the conduct of the study; personal fees from Astellas Pharma. Inc., grants and personal fees from Bristol-Myers Squibb Co., Ltd., grants and personal fees from Celgene Co., Ltd., personal fees from Chugai Pharmaceutical Co., Ltd., personal fees from CIMIC Co., Ltd., personal fees from Eli Lilly Japan, grants and personal fees from Fujimoto Pharmaceutical Co., Ltd., personal fees from Huya Bioscience International, personal fees from Janssen Pharmaceutical Co., Ltd., personal fees from Kyowa Hakko Kirin Co., Ltd., personal fees from Nippon Boehringer-Ingelheim Co., Ltd., grants from Nippon Shinyaku Pharmaceutical Co., Ltd., grants from Novartis Pharma, grants and personal fees from Otsuka Pharmaceutical Co., Ltd., grants and personal fees from Pfizer Co., Ltd., personal fees from SymBio Pharmaceuticals Co., Ltd., grants and personal fees from Sysmex Co., Ltd., personal fees from Takeda Bio Development Center Ltd., personal fees from Zenyaku Kogyo Co., Ltd., outside the submitted work. Dr. Kobayashi reports grants from Kyowa Kirin, grants from Shionogi, grants from Zenyaku Kogyo, grants from Taiho Pharma, grants from Chugai Pharmaceutical, grants from Asahi Kasei Pharma, grants from Astellas, grants from Eisai, grants from Ono Pharmaceutical, grants from Toyama Chemical, grants from Takeda Pharmaceutical, grants from MSD, outside the submitted work. Dr. Ogawa reports grants and personal fees from KAN Research Institute, Inc., other from Asahi Genomics Co., Ltd., grants from Nippon Shinyaku Co., Ltd., grants from Takeda Pharmaceutical Co., Ltd., outside the submitted work. Dr. Naoe reports grants from Fujifilm Corporation, outside the submitted work; In addition, Dr. Naoe has a patent null pending. Dr. Kiyoi reports grants from AMED, grants from National Cancer Center Research and Development Fund, during the conduct of the study; grants from Chugai Pharmaceutical Co., Ltd., grants and personal fees from Bristol-Myers Squibb, grants from Kyowa Hakko Kirin Co., Ltd., grants from Zenyaku Kogyo Co., Ltd., grants from FUJIFILM Corporation, grants from Nippon Boehringer Ingelheim Co., Ltd., grants and personal fees from Astellas Pharma Inc., grants from Celgene Corporation, personal fees from Daiichi Sankyo Co., Ltd., grants and personal fees from Pfizer Japan Inc, grants from Nippon Shinyaku Co., Ltd., grants from Eisai Co., Ltd., grants from Takeda Pharmaceutical Co., Ltd., grants from Ono Pharmaceutical Co., Ltd., grants from Japan Blood Products Organization, outside the submitted work. The other authors declare no competing financial interests.
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Kuwatsuka, Y., Tomizawa, D., Kihara, R. et al. Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia. Int J Hematol 107, 201–210 (2018). https://doi.org/10.1007/s12185-017-2340-z
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DOI: https://doi.org/10.1007/s12185-017-2340-z