International Journal of Hematology

, Volume 107, Issue 2, pp 201–210 | Cite as

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
Original Article

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 

Notes

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).

Compliance with ethical standards

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.

Supplementary material

12185_2017_2340_MOESM1_ESM.pdf (183 kb)
Supplementary material 1 (PDF 183 kb)

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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Yachiyo Kuwatsuka
    • 1
  • Daisuke Tomizawa
    • 2
  • Rika Kihara
    • 3
  • Yasunobu Nagata
    • 4
  • Norio Shiba
    • 5
  • Yuka Iijima-Yamashita
    • 6
  • Akira Shimada
    • 7
  • Takao Deguchi
    • 8
  • Hayato Miyachi
    • 9
  • Akio Tawa
    • 10
  • Takashi Taga
    • 11
  • Akitoshi Kinoshita
    • 12
  • Hideki Nakayama
    • 13
  • Nobutaka Kiyokawa
    • 14
  • Akiko Moriya Saito
    • 6
  • Katsuyoshi Koh
    • 15
  • Hiroaki Goto
    • 16
  • Yoshiyuki Kosaka
    • 17
  • Norio Asou
    • 18
  • Shigeki Ohtake
    • 19
  • Shuichi Miyawaki
    • 20
  • Yasushi Miyazaki
    • 21
  • Toru Sakura
    • 22
  • Yukiyasu Ozawa
    • 23
  • Noriko Usui
    • 24
  • Heiwa Kanamori
    • 25
  • Yoshikazu Ito
    • 26
  • Kiyotoshi Imai
    • 27
  • Youko Suehiro
    • 28
  • Shinichi Kobayashi
    • 29
  • Kunio Kitamura
    • 30
  • Emiko Sakaida
    • 31
  • Seishi Ogawa
    • 32
    • 33
  • Tomoki Naoe
    • 3
    • 34
  • Yasuhide Hayashi
    • 35
  • Keizo Horibe
    • 6
  • Atsushi Manabe
    • 36
  • Shuki Mizutani
    • 37
  • Souichi Adachi
    • 38
  • Hitoshi Kiyoi
    • 3
  1. 1.Center for Advanced Medicine and Clinical ResearchNagoya University HospitalNagoyaJapan
  2. 2.Division of Leukemia and Lymphoma, Children’s Cancer CenterNational Center for Child Health and DevelopmentTokyoJapan
  3. 3.Department of Hematology and OncologyNagoya University Graduate School of MedicineNagoyaJapan
  4. 4.Department of Translational Hematology and Oncology Research, Taussig Cancer InstituteCleveland ClinicClevelandUSA
  5. 5.Department of PediatricsYokohama City University Hospital, Graduate School of MedicineYokohamaJapan
  6. 6.Clinical Research CenterNational Hospital Organization Nagoya Medical CenterNagoyaJapan
  7. 7.Department of PediatricsOkayama University HospitalOkayamaJapan
  8. 8.Department of PediatricsMie University Graduate School of MedicineTsuJapan
  9. 9.Department of Laboratory MedicineTokai University School of MedicineIseharaJapan
  10. 10.Department of PediatricsNational Hospital Organization, Osaka National HospitalOsakaJapan
  11. 11.Department of PediatricsShiga University of Medical ScienceOtsuJapan
  12. 12.Department of PediatricsSt. Marianna University School of MedicineKawasakiJapan
  13. 13.Department of PediatricsNational Hospital Organization, Kyushu Cancer CenterFukuokaJapan
  14. 14.Department of Pediatric Hematology and Oncology ResearchNational Research Institute for Child Health and DevelopmentTokyoJapan
  15. 15.Department of Hematology/OncologySaitama Children’s Medical CenterSaitamaJapan
  16. 16.Division of Hemato-Oncology and Regenerative MedicineKanagawa Children’s Medical CenterYokohamaJapan
  17. 17.Department of Hematology and OncologyHyogo Prefectural Kobe Children’s HospitalKobeJapan
  18. 18.Department of Hematology, International Medical CenterSaitama Medical UniversityHidakaJapan
  19. 19.Kanazawa UniversityKanazawaJapan
  20. 20.Division of HematologyTokyo Metropolitan Ohtsuka HospitalTokyoJapan
  21. 21.Department of Hematology, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  22. 22.Leukemia Research CenterSaiseikai Maebashi HospitalMaebashiJapan
  23. 23.Department of HematologyJapanese Red Cross Nagoya First HospitalNagoyaJapan
  24. 24.Division of Clinical Oncology and Hematology, Department of Internal MedicineJikei University School of MedicineTokyoJapan
  25. 25.Department of HematologyKanagawa Cancer CenterKanagawaJapan
  26. 26.Department of HematologyTokyo Medical UniversityTokyoJapan
  27. 27.Department of HematologySapporo Hokuyu HospitalSapporoJapan
  28. 28.Department of HematologyNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
  29. 29.Division of Hematology, Department of Internal MedicineNational Defense Medical CollegeSaitamaJapan
  30. 30.Division of HematologyIchinomiya Municipal HospitalIchinomiyaJapan
  31. 31.Department of HematologyChiba University HospitalChibaJapan
  32. 32.Cancer Genomics Project, Graduate School of MedicineThe University of TokyoTokyoJapan
  33. 33.Department of Pathology and Tumor Biology, Graduate School of MedicineKyoto UniversityKyotoJapan
  34. 34.National Hospital Organization Nagoya Medical CenterNagoyaJapan
  35. 35.Department of Hematology/OncologyGunma Children’s Medical CenterGunmaJapan
  36. 36.Department of PediatricsSt. Luke’s International HospitalTokyoJapan
  37. 37.Department of Pediatrics and Developmental BiologyTokyo Medical and Dental UniversityTokyoJapan
  38. 38.Human Health SciencesKyoto UniversityKyotoJapan

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