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

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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.

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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).

Author information

Author notes

  1. Yachiyo Kuwatsuka and Daisuke Tomizawa contributed equally to this work.

Authors and Affiliations

  1. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan

    Yachiyo Kuwatsuka

  2. Division of Leukemia and Lymphoma, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Daisuke Tomizawa

  3. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Rika Kihara, Tomoki Naoe & Hitoshi Kiyoi

  4. Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    Yasunobu Nagata

  5. Department of Pediatrics, Yokohama City University Hospital, Graduate School of Medicine, Yokohama, Japan

    Norio Shiba

  6. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Yuka Iijima-Yamashita, Akiko Moriya Saito & Keizo Horibe

  7. Department of Pediatrics, Okayama University Hospital, Okayama, Japan

    Akira Shimada

  8. Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan

    Takao Deguchi

  9. Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Japan

    Hayato Miyachi

  10. Department of Pediatrics, National Hospital Organization, Osaka National Hospital, Osaka, Japan

    Akio Tawa

  11. Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan

    Takashi Taga

  12. Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan

    Akitoshi Kinoshita

  13. Department of Pediatrics, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan

    Hideki Nakayama

  14. Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan

    Nobutaka Kiyokawa

  15. Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan

    Katsuyoshi Koh

  16. Division of Hemato-Oncology and Regenerative Medicine, Kanagawa Children’s Medical Center, Yokohama, Japan

    Hiroaki Goto

  17. Department of Hematology and Oncology, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan

    Yoshiyuki Kosaka

  18. Department of Hematology, International Medical Center, Saitama Medical University, Hidaka, Japan

    Norio Asou

  19. Kanazawa University, Kanazawa, Japan

    Shigeki Ohtake

  20. Division of Hematology, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan

    Shuichi Miyawaki

  21. Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Yasushi Miyazaki

  22. Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan

    Toru Sakura

  23. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Yukiyasu Ozawa

  24. Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Noriko Usui

  25. Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan

    Heiwa Kanamori

  26. Department of Hematology, Tokyo Medical University, Tokyo, Japan

    Yoshikazu Ito

  27. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Kiyotoshi Imai

  28. Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Youko Suehiro

  29. Division of Hematology, Department of Internal Medicine, National Defense Medical College, Saitama, Japan

    Shinichi Kobayashi

  30. Division of Hematology, Ichinomiya Municipal Hospital, Ichinomiya, Japan

    Kunio Kitamura

  31. Department of Hematology, Chiba University Hospital, Chiba, Japan

    Emiko Sakaida

  32. Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Seishi Ogawa

  33. Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Seishi Ogawa

  34. National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Tomoki Naoe

  35. Department of Hematology/Oncology, Gunma Children’s Medical Center, Gunma, Japan

    Yasuhide Hayashi

  36. Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan

    Atsushi Manabe

  37. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan

    Shuki Mizutani

  38. Human Health Sciences, Kyoto University, Kyoto, Japan

    Souichi Adachi

Authors
  1. Yachiyo Kuwatsuka
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  2. Daisuke Tomizawa
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  3. Rika Kihara
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  39. Souichi Adachi
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  40. Hitoshi Kiyoi
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Corresponding author

Correspondence to Yachiyo Kuwatsuka.

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Conflict of interest

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

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