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Allogeneic hematopoietic stem cell transplantation for children and adolescents with high-risk cytogenetic AML: distinctly poor outcomes of FUS-ERG-positive cases

Bone Marrow Transplantation volume 54, pages 393–401 (2019)Cite this article

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Abstract

Allocating patients with acute myeloid leukemia and high-risk cytogenetic abnormalities (HR-AML) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is part of the standard treatment protocol; however, whether allo-HSCT truly improves the outcomes in these patients is debatable. Data on 169 children and adolescents with HR-AML who received their first allo-HSCT in first or second remission between 2000 and 2015 were extracted from a nationwide, Japanese HSCT registry. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 55.2% (95% CI, 46.8–62.9%) and 69.6% (61.4–76.3%), respectively, for all the HR-AML patients. In univariate analysis, the cytogenetic subgroup had a significant impact on both the DFS (P = 0.011) and OS (P < 0.001) rates. In particular, 14 patients with t(16;21) showed an extremely poor outcome. Additionally, older age at allo-HSCT (10–19 years old, P = 0.025), myeloablative conditioning with total-body irradiation (P = 0.019), and grade II–IV acute graft-versus-host disease (GVHD, P = 0.049) were associated with inferior OS. The donor type and occurrence of chronic GVHD did not affect the outcome. Multivariate analysis revealed t(16;21) to be associated with increased overall mortality (hazard ratio = 4.416, P < 0.001). Because the outcome of patients with certain HR-AML subgroups, such as t(16;21)-positive cases, is extremely poor even with allo-HSCT in remission, a novel therapy is urgently required.

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Acknowledgements

The authors thank all the members of the hospitals and centers who contributed valuable data to the JSHCT registry. The authors also thank Mr. JR Valera of the Department of Education for Clinical Research, National Center for Child Health and Development, for his assistance in editing this manuscript. This work was supported by a grant for Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (AMED) and a grant from the National Center for Child Health and Development (30-1).

Author contributions

DT, MY, TK, TM, TT, SA, and HI participated actively in the study conception and design; DT conducted the data analysis and interpretation and was the main author of the study; KK, MN, HK, KW, YC, TF, MK, NS, HG, JH, and MI provided patient data; MI, YH, YA, and HI contributed to the administrative support of the study; and all the authors contributed to carrying out the study, were involved in the review of the results, and gave their final approval of the manuscript.

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Authors and Affiliations

  1. Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Daisuke Tomizawa & Motohiro Kato

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

    Masanori Yoshida & Motohiro Kato

  3. Department of Hematology and Oncology, Kyoto University, Kyoto, Japan

    Tadakazu Kondo

  4. Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan

    Takako Miyamura & Yoshiko Hashii

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

    Takashi Taga

  6. Department of Human Health Sciences, Kyoto University, Kyoto, Japan

    Souichi Adachi

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

    Katsuyoshi Koh

  8. Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan

    Maiko Noguchi

  9. Department of Hematology/Oncology, Chiba Children’s Hospital, Chiba, Japan

    Harumi Kakuda

  10. Department of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan

    Kenichiro Watanabe

  11. Department of Pediatrics, Hokkaido University Hospital, Sapporo, Japan

    Yuko Cho

  12. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

  13. Department of Pediatrics, Yokohama City University Hospital, Yokohama, Japan

    Norio Shiba

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

    Hiroaki Goto

  15. Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan

    Keiko Okada

  16. Department of Hematology/Oncology, Osaka Women’s and Children’s Hospital, Osaka, Japan

    Masami Inoue

  17. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

  18. Department of Healthcare Administration, Nagoya University, Nagoya, Japan

    Yoshiko Atsuta

  19. Department of Pediatrics, Kyoto City Hospital, Kyoto, Japan

    Hiroyuki Ishida

Authors
  1. Daisuke Tomizawa
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  2. Masanori Yoshida
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  15. Hiroaki Goto
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  16. Keiko Okada
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  18. Yoshiko Hashii
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  19. Yoshiko Atsuta
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  20. Hiroyuki Ishida
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Correspondence to Daisuke Tomizawa.

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Tomizawa, D., Yoshida, M., Kondo, T. et al. Allogeneic hematopoietic stem cell transplantation for children and adolescents with high-risk cytogenetic AML: distinctly poor outcomes of FUS-ERG-positive cases. Bone Marrow Transplant 54, 393–401 (2019). https://doi.org/10.1038/s41409-018-0273-7

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  • DOI: https://doi.org/10.1038/s41409-018-0273-7

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