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

Yachiyo Kuwatsuka¹, Daisuke Tomizawa², Rika Kihara³, Yasunobu Nagata⁴, Norio Shiba⁵, Yuka Iijima-Yamashita⁶, Akira Shimada⁷, Takao Deguchi⁸, Hayato Miyachi⁹, Akio Tawa¹⁰, Takashi Taga¹¹, Akitoshi Kinoshita¹², Hideki Nakayama¹³, Nobutaka Kiyokawa¹⁴, Akiko Moriya Saito⁶, Katsuyoshi Koh¹⁵, Hiroaki Goto¹⁶, Yoshiyuki Kosaka¹⁷, Norio Asou¹⁸, Shigeki Ohtake¹⁹, Shuichi Miyawaki²⁰, Yasushi Miyazaki²¹, Toru Sakura²², Yukiyasu Ozawa²³, Noriko Usui²⁴, Heiwa Kanamori²⁵, Yoshikazu Ito²⁶, Kiyotoshi Imai²⁷, Youko Suehiro²⁸, Shinichi Kobayashi²⁹, Kunio Kitamura³⁰, Emiko Sakaida³¹, Seishi Ogawa^{32

33}, Tomoki Naoe^{3

34}, Yasuhide Hayashi³⁵, Keizo Horibe⁶, Atsushi Manabe³⁶, Shuki Mizutani³⁷, Souichi Adachi³⁸, Hitoshi Kiyoi³

Affiliations

¹ Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. ykuwatsuka@med.nagoya-u.ac.jp.
² Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
³ Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁴ Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
⁵ Department of Pediatrics, Yokohama City University Hospital, Graduate School of Medicine, Yokohama, Japan.
⁶ Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
⁷ Department of Pediatrics, Okayama University Hospital, Okayama, Japan.
⁸ Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
⁹ Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Japan.
¹⁰ Department of Pediatrics, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
¹¹ Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan.
¹² Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan.
¹³ Department of Pediatrics, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan.
¹⁴ Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
¹⁵ Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
¹⁶ Division of Hemato-Oncology and Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
¹⁷ Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
¹⁸ Department of Hematology, International Medical Center, Saitama Medical University, Hidaka, Japan.
¹⁹ Kanazawa University, Kanazawa, Japan.
²⁰ Division of Hematology, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan.
²¹ Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
²² Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan.
²³ Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
²⁴ Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
²⁵ Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan.
²⁶ Department of Hematology, Tokyo Medical University, Tokyo, Japan.
²⁷ Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
²⁸ Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
²⁹ Division of Hematology, Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
³⁰ Division of Hematology, Ichinomiya Municipal Hospital, Ichinomiya, Japan.
³¹ Department of Hematology, Chiba University Hospital, Chiba, Japan.
³² Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³³ Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
³⁴ National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
³⁵ Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan.
³⁶ Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
³⁷ Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
³⁸ Human Health Sciences, Kyoto University, Kyoto, Japan.

PMID: 29027108
DOI: 10.1007/s12185-017-2340-z

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

Yachiyo Kuwatsuka et al. Int J Hematol. 2018 Feb.

. 2018 Feb;107(2):201-210.

doi: 10.1007/s12185-017-2340-z. Epub 2017 Oct 12.

Authors

Affiliations

¹ Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. ykuwatsuka@med.nagoya-u.ac.jp.
² Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
³ Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁴ Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
⁵ Department of Pediatrics, Yokohama City University Hospital, Graduate School of Medicine, Yokohama, Japan.
⁶ Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
⁷ Department of Pediatrics, Okayama University Hospital, Okayama, Japan.
⁸ Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
⁹ Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Japan.
¹⁰ Department of Pediatrics, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
¹¹ Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan.
¹² Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan.
¹³ Department of Pediatrics, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan.
¹⁴ Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
¹⁵ Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
¹⁶ Division of Hemato-Oncology and Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
¹⁷ Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
¹⁸ Department of Hematology, International Medical Center, Saitama Medical University, Hidaka, Japan.
¹⁹ Kanazawa University, Kanazawa, Japan.
²⁰ Division of Hematology, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan.
²¹ Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
²² Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan.
²³ Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
²⁴ Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
²⁵ Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan.
²⁶ Department of Hematology, Tokyo Medical University, Tokyo, Japan.
²⁷ Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
²⁸ Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
²⁹ Division of Hematology, Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
³⁰ Division of Hematology, Ichinomiya Municipal Hospital, Ichinomiya, Japan.
³¹ Department of Hematology, Chiba University Hospital, Chiba, Japan.
³² Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³³ Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
³⁴ National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
³⁵ Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan.
³⁶ Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
³⁷ Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
³⁸ Human Health Sciences, Kyoto University, Kyoto, Japan.

PMID: 29027108
DOI: 10.1007/s12185-017-2340-z

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.

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

Affiliations

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

Authors

Affiliations

Abstract

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Miscellaneous