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Conditioning regimen for allogeneic bone marrow transplantation in children with acquired bone marrow failure: fludarabine/melphalan vs. fludarabine/cyclophosphamide

Bone Marrow Transplantation volume 55, pages 1272–1281 (2020)Cite this article

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Abstract

Fludarabine/cyclophosphamide-based conditioning regimens are standard in bone marrow transplantation (BMT) for acquired bone marrow failure in children, however, graft failure may occur. Using the data from a nationwide transplantation registry, we compared the outcomes of children aged <16 years with acquired aplastic anemia and refractory cytopenia of childhood who underwent allogeneic BMT with either fludarabine/melphalan (n = 71) or fludarabine/cyclophosphamide (n = 296) between 2000 and 2016. The fludarabine/melphalan regimen provided excellent outcomes, with 3-year overall survival and failure-free survival rates of 98% and 97%, respectively. The 83% 3-year failure-free survival in the fludarabine/cyclophosphamide group was significantly inferior (P = 0.002), whereas the overall survival did not differ between the two groups. Late graft failure was the most common cause of treatment failure in the fludarabine/cyclophosphamide group, which experienced a significantly higher incidence of late graft failure than the fludarabine/melphalan group (11% vs. 3%; P = 0.035). Multivariate analyses showed that the fludarabine/melphalan regimen was associated with a better failure-free survival (hazard ratio [HR] 0.12; P = 0.005) and lower risk of late graft failure (HR 0.16; P = 0.037). Fludarabine/melphalan-based conditioning regimen can be a promising option for children with acquired bone marrow failure receiving BMT.

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Fig. 1: Survivals after bone marrow transplantation in pediatric acquired bone marrow failure according to conditioning regimen: fludarabine (FLU)/melphalan (MEL)-based (n = 71) or FLU/cyclophosphamide (CY)-based (n = 296).
Fig. 2: Cumulative incidences of late graft failure (LGF) and donor-type aplasia according to conditioning regimen: FLU/MEL (n = 71) or FLU/CY (n = 296).

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Acknowledgements

The authors would like to thank all of the patients and families, and also thank all physicians and members who provided precise data to the Japan Society for Hematopoietic Cell Transplantation. This research was funded by Japanese Red Cross, Nagoya 1st. Hospital Research Grant NFRCH19-0019 (to NY) and was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development, AMED under grant number 19ek0510023h0002 (to YA).

Pediatric Aplastic Anemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Nao Yoshida1, Yoshiyuki Takahashi2, Hiromasa Yabe3, Ryoji Kobayashi4, Kenichiro Watanabe5, Kazuko Kudo6, Keisuke Kato19, Hideki Muramatsu2, Atsushi Narita2, Manabu Wakamatsu2, Seiji Kojima2

Author information

Authors and Affiliations

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

    Nao Yoshida & Nao Yoshida

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

    Yoshiyuki Takahashi, Seiji Kojima, Yoshiyuki Takahashi, Hideki Muramatsu, Atsushi Narita, Manabu Wakamatsu & Seiji Kojima

  3. Department of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan

    Hiromasa Yabe, Miharu Yabe & Hiromasa Yabe

  4. Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan

    Ryoji Kobayashi & Ryoji Kobayashi

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

    Kenichiro Watanabe & Ken-ichiro Watanabe

  6. Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan

    Kazuko Kudo & Kazuko Kudo

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

    Takako Miyamura

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

    Katsuyoshi Koh

  9. Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan

    Hiroshi Kawaguchi

  10. Division of Hematology/Oncology, Kanagawa Children’s Medical Center, Yokohama, Japan

    Hiroaki Goto

  11. Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan

    Naoto Fujita

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

    Keiko Okada

  13. Department of Pediatrics, Kagoshima University Hospital, Kagoshima, Japan

    Yasuhiro Okamoto

  14. Central Japan Cord Blood Bank, Seto, Japan

    Koji Kato

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

    Masami Inoue

  16. Department of HSCT Data Management & Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Ritsuro Suzuki

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

    Yoshiko Atsuta

  18. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiko Atsuta

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

    Keisuke Kato

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  1. Nao Yoshida
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  2. Yoshiyuki Takahashi
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on behalf of the Pediatric Aplastic Anemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

  • Nao Yoshida
  • , Yoshiyuki Takahashi
  • , Hiromasa Yabe
  • , Ryoji Kobayashi
  • , Ken-ichiro Watanabe
  • , Kazuko Kudo
  • , Keisuke Kato
  • , Hideki Muramatsu
  • , Atsushi Narita
  • , Manabu Wakamatsu
  •  & Seiji Kojima

Contributions

NY and SK designed research, analyzed and interpreted data, and wrote the manuscript; YT, HY, RK, KW, KKu, and MY interpreted data; TM, KKo, HK, HG, NF, KO, YO, KKa, MI, RS, and YA collected and organized data; all authors reviewed and approved the final manuscript.

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Correspondence to Nao Yoshida.

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Members of the Pediatric Aplastic Anemia Working Group of the Japan Society for Hematopoietic Cell Transplantation are listed below Acknowledgements.

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Yoshida, N., Takahashi, Y., Yabe, H. et al. Conditioning regimen for allogeneic bone marrow transplantation in children with acquired bone marrow failure: fludarabine/melphalan vs. fludarabine/cyclophosphamide. Bone Marrow Transplant 55, 1272–1281 (2020). https://doi.org/10.1038/s41409-020-0948-8

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