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ACUTE MYELOID LEUKEMIA

Allogeneic hematopoietic stem cell transplantation in adult acute myeloid leukemia with t(16;21)(p11;q22)/FUS::ERG

Leukemia volume 39, pages 495–498 (2025)Cite this article

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The t(16;21)(p11;q22) translocation is a rare but non-random chromosomal abnormality that accounts for approximately 1% of cases of acute myeloid leukemia (AML) [1, 2]. This chromosomal translocation produces a fusion gene between the FUS gene at chromosome 16p11 and the ERG gene at chromosome 21q22. Recent cytogenetic stratification classifies the sole abnormality of t(16;21)(p11;q22) as intermediate risk [1]. However, previous reports [2,3,4] suggest that the prognosis for AML patients with t(16;21)(p11;q22) is generally significantly worse, and evidence regarding allogeneic hematopoietic stem cell transplantation (HSCT) for AML patients with t(16;21)(p11;q22) is still lacking. Therefore, this study evaluated the survival outcomes of AML with t(16;21)(p11;q22) after allogeneic HSCT and compared them with those of other AML patients using Japanese transplant registry data.

The clinical data were provided by the Transplant Registry Unified Management Program 2 of the Japan Society for Transplantation and the Cellular Therapy and the Japanese Data Center for Hematopoietic Cell Transplantation [5,6,7]. Our study included patients with AML aged ≥16 years who received their first allogeneic HSCT between 1986 and 2021. Patients with a favorable-risk karyotype were excluded, as t(16;21)(p11;q22) is not classified as favorable according to the karyotype risk classification. This study was approved by the Data Management Committee of the Japanese Data Center for Hematopoietic Cell Transplantation and the Ethics Committee of Kobe City Medical Center General Hospital. Cytogenetic information was obtained at diagnosis or before allogeneic HSCT. The cytogenetic risk was classified as favorable, intermediate, or poor in accordance with the criteria provided by the National Comprehensive Cancer Network Guidelines (Version 1.2016) [8]. Due to insufficient data, in some cases, the t(16;21) translocation was identified, but their breakpoints were unknown (t(16;21) BU [breakpoint unknown]). Chromosomal translocations involving chromosomes 16 and 21 seen in AML include t(16;21)(q24;q22), as well as t(16;21)(p11;q22) [9]. However, t(16;21)(q24;q22) is notably rare in adult AML [3, 4, 9]; therefore, we considered t(16;21) BU as t(16;21)(p11;q22) in our analysis. Additionally, we performed a sensitivity analysis comparing patient characteristics and survival data between the t(16;21) BU and t(16;21)(p11;q22) groups to identify potential misclassifications. Other detailed definitions of variables and endpoints are described in Supplementary materials. The study endpoints were progression-free survival (PFS), overall survival (OS), relapse, and non-relapse mortality (NRM). For survival analysis, the Kaplan–Meier method was used for OS and PFS, while the Gray’s method was used for relapse and NRM to account for competing risks. Multivariable analysis was performed using a Cox proportional hazard model for OS and PFS or a Fine and Gray proportional hazard model for relapse and NRM. The Fine and Gray method was used to consider competing risks. Statistical significance was set at P < 0.05. All statistical analyses were performed using the R software (version 4.3.2; R Development Core Team).

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Fig. 1: Transplant outcomes within each of the intermediate- and poor-risk subgroups.

Data availability

The data used in this study are not publicly available because of ethical restrictions that exceed the scope of the recipient/donor’s consent for research use in the registry. Data may be available from the corresponding author upon reasonable request and with permission of the Japan Society for Transplantation and the Cellular Therapy and the Japanese Data Center for Hematopoietic Cell Transplantation.

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Acknowledgements

The authors appreciate all the physicians and data managers at the centers that contributed to data collection for the Japanese Data Center for Hematopoietic Cell Transplantation and Transplant Registry Unified Management Program 2.

Author information

Authors and Affiliations

  1. Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan

    Satoshi Mitsuyuki & Yoshimitsu Shimomura

  2. Department of Environmental Medicine and Population Science, Graduate School of Medicine, Osaka University, Osaka, Japan

    Yoshimitsu Shimomura

  3. Department of Hematology, Kanazawa University, Kanazawa, Japan

    Hiroki Mizumaki

  4. Department of Hematology and Oncology, Nagoya City University East Medical Center, Nagoya, Japan

    Masamitsu Yanada

  5. Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan

    Shohei Mizuno

  6. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida

  7. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Noriko Doki

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

    Ayumu Ito & Takahiro Fukuda

  9. Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan

    Masatsugu Tanaka

  10. Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan

    Tetsuya Nishida

  11. Department of Hematology, Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan

    Yuta Katayama

  12. Department of Hematology, Hyogo Medical University Hospital, Nishinomiya, Japan

    Satoshi Yoshihara

  13. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Tetsuya Eto

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

    Satoru Takada

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

    Shuichi Ota

  16. Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan

    Masako Toyosaki & Makoto Onizuka

  17. Department of Hematology, Hokkaido University Hospital, Sapporo, Japan

    Yuta Hasegawa

  18. Department of Hematology, Osaka Metropolitan University Hospital, Osaka, Japan

    Hirohisa Nakamae

  19. Division of Clinical Laboratory Medicine, Department of Multidisciplinary Internal Medicine, Tottori University, Tottori, Japan

    Koji Kawamura

  20. Japanese Data Center for Hematopoietic Cell Transplantation, Nagakute, Japan

    Marie Ohbiki & Yoshiko Atsuta

  21. Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan

    Marie Ohbiki & Yoshiko Atsuta

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

    Marie Ohbiki

  23. Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Takaaki Konuma

Authors
  1. Satoshi Mitsuyuki
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  2. Yoshimitsu Shimomura
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  3. Hiroki Mizumaki
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  4. Masamitsu Yanada
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  5. Shohei Mizuno
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  9. Masatsugu Tanaka
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  23. Yoshiko Atsuta
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  24. Takaaki Konuma
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Contributions

Satoshi Mitsuyuki designed the study, performed statistical analyses, and wrote the manuscript. YS supervised the study design, statistical analyses, and manuscript writing. TK, HM, MY, and SM critically reviewed the analyzed data and manuscript. NM, ND, AI, MT, TN, YK, SY, TE, ST, SO, MT, YH, HN, KK, MO, TF, MO, and YA contributed to the data collection. All the authors approved the final version of the manuscript.

Corresponding author

Correspondence to Satoshi Mitsuyuki.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Japanese Data Center for Hematopoietic Cell Transplantation and the Institutional Review Board of Kobe City Medical Center General Hospital and conducted in accordance with the Declaration of Helsinki (approval number: zn240506). Written informed consent was obtained from each patient at each institution before Transplant Registry Unified Management Program 2 registration.

Competing interests

Shohei Mizuno received research funding from Hayashikane Sangyo and lecture fees from Janssen Pharmaceutical. The other authors declare no conflicts of interest associated with this manuscript.

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Mitsuyuki, S., Shimomura, Y., Mizumaki, H. et al. Allogeneic hematopoietic stem cell transplantation in adult acute myeloid leukemia with t(16;21)(p11;q22)/FUS::ERG. Leukemia 39, 495–498 (2025). https://doi.org/10.1038/s41375-024-02495-1

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