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Graft-versus-host disease-free, relapse-free, second transplant-free survival in allogeneic hematopoietic cell transplantation for genetic disorders

Bone Marrow Transplantation volume 58, pages 600–602 (2023)Cite this article

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Similar to its application in hematologic malignancies (HMs), allogeneic hematopoietic cell transplantation (HCT) has also been widely employed as a curative therapy for genetic disorders (GDs), including inherited bone marrow failure syndrome (IBMFS), inherited metabolic disease (IMD), and primary immunodeficiency (PID); however, there are several fundamental differences between HCT for GDs and HMs [1, 2]. First, the intensity of the conditioning regimen required to improve disease differs between GDs and HMs. Second, patients with GDs bear higher risk of graft failure (GF) or mixed chimerism (MC) following HCT, and derive little, if any, survival benefit from graft-versus-host disease (GVHD)-associated graft-versus-tumor effects. Third, due to the higher overall survival (OS) rate (>80%) of patients with GDs, greater attention has been paid to late adverse effects and decreased of quality of life after HCT in these patients [3].

In patients with GDs treated by HCT, the major critical events (death, GVHD, GF, and MC) are not fully assessed by conventional endpoints, such as OS. In HCT for HMs, GVHD-free and relapse-free survival (GRFS), defined as the absence of grade III–IV acute GVHD, systemically treated chronic GVHD, relapse, and death, was developed as a composite endpoint [4, 5]. In a recent paper, relapse-free survival was replaced with GF-free survival as a component of GRFS to more precisely assess transplant outcomes for patients with aplastic anemia [6, 7]. Therefore, we hypothesized that second transplantation, principally indicated for MC, would be a meaningful event to evaluate the success of HCT for GDs. In the current study, we retrospectively analyzed the clinical outcomes of patients with GDs who underwent first HCT using a novel composite endpoint, GVHD-free, relapse (i.e., primary/secondary GF)-free, and second transplant-free survival (GRSFS), comprising grade III–IV acute GVHD, systemically treated chronic GVHD, relapse, second transplantation, and nonrelapse mortality (NRM) as failure events. Details of the methods are provided in the Supplementary information.

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Fig. 1: OS, GRSFS, cumulative incidence of individual failure events in the entire cohort, and engraftment of blood cells after transplantation from ABO-matched or -mismatched donors.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all the physicians and data managers at the transplant centers who contributed data to the Transplant Registry Unified Management Program (TRUMP) of the Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT) and the Japanese Society for Transplantation and Cellular Therapy (JSTCT).

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Authors and Affiliations

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

    Koji Kawaguchi

  2. Inherited Disorder Working Group of the Japanese Society for Transplantation and Cellular Therapy, Nagoya, Japan

    Koji Kawaguchi, Katsutsugu Umeda, Satoshi Miyamoto, Nao Yoshida, Hiromasa Yabe & Kohsuke Imai

  3. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Katsutsugu Umeda

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

    Satoshi Miyamoto, Michiko Kajiwara & Kohsuke Imai

  5. Department of Hematology and Oncology, Children’s Medical Center, Japanese Red Cross Aichi Medical Center Nagoya First Hospital, Nagoya, Japan

    Nao Yoshida & Asahito Hama

  6. Department of Pediatrics, Tokai University School of Medicine, Isehara, Japan

    Hiromasa Yabe & Takashi Koike

  7. Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Science, Hiroshima, Japan

    Hiroshi Kawaguchi

  8. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiyuki Takahashi

  9. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masataka Ishimura

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

    Hirotoshi Sakaguchi

  11. Department of Pediatrics, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Yuko Cho

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

    Maho Sato

  13. Division of Pediatric Hematology and Oncology, Ibaraki Children’s Hospital, Mito, Japan

    Keisuke Kato

  14. Department of Hematology and Oncology, Miyagi Children’s Hospital, Sendai, Japan

    Atsushi Sato

  15. Central Japan Cord Blood Bank, Seto, Japan

    Koji Kato

  16. Division of Pediatrics, Tokyo Metropolitan Cancer and Infectious Disease Komagome Hospital, Tokyo, Japan

    Ken Tabuchi

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

    Yoshiko Atsuta

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

    Yoshiko Atsuta

  19. Department of Pediatrics, National Medical Defense College, Tokorozawa, Japan

    Kohsuke Imai

Authors
  1. Koji Kawaguchi
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  13. Yuko Cho
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  16. Atsushi Sato
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  17. Koji Kato
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  18. Ken Tabuchi
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  19. Yoshiko Atsuta
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  20. Kohsuke Imai
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Contributions

K Kawaguchi, KU, SM, NY, HY, and KI designed the research and organized the project; K Kawaguchi and KU performed statistical analysis and analyzed the data; TK, MK, HK, YT, MI, HS, AH, YC, MS, Keisuke Kato, AS, Koji Kato, KT, and YA gathered and organized the data; K Kawaguchi and KU wrote the manuscript. All authors interpreted the data and reviewed and approved the manuscript.

Corresponding author

Correspondence to Katsutsugu Umeda.

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The authors declare no competing interests.

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Kawaguchi, K., Umeda, K., Miyamoto, S. et al. Graft-versus-host disease-free, relapse-free, second transplant-free survival in allogeneic hematopoietic cell transplantation for genetic disorders. Bone Marrow Transplant 58, 600–602 (2023). https://doi.org/10.1038/s41409-023-01937-1

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  • DOI: https://doi.org/10.1038/s41409-023-01937-1

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