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Impact of low-dose irradiation and in vivo T-cell depletion on hematopoietic stem cell transplantation for non-malignant diseases using fludarabine-based reduced-intensity conditioning

Bone Marrow Transplantation volume 54, pages 1227–1236 (2019)Cite this article

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Abstract

Reduced-intensity conditioning is widely used with hematopoietic stem cell transplantation for non-malignant diseases: however, the optimal conditioning to ensure stable engraftment has not been established. In this study, we retrospectively compared the impact of low-dose (1–6 Gy) irradiation and in vivo T-cell depletion on the clinical outcome of 523 patients with non-malignant disease who underwent a first allogeneic hematopoietic stem cell transplantation using fludarabine-based reduced-intensity conditioning. Use of low-dose irradiation, but not of anti-thymocyte globulin/anti-lymphocyte globulin, showed a beneficial effect on overall survival (adjusted hazard ratio: 0.56; 95% confidence interval: 0.35–0.91, P = 0.018). Furthermore, use of low-dose irradiation was strongly associated with lower transplant-related mortality (adjusted hazard ratio: 0.55; 95% confidence interval: 0.32–0.96, P = 0.034). The addition of low-dose irradiation to the conditioning regimen was beneficial, at least to the short-term clinical outcome. A large prospective study with long-term follow-up is now required to extend these findings and establish the optimal hematopoietic stem cell transplant conditioning for patients with at least some subgroups of non-malignant diseases.

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Acknowledgements

We thank all the physicians and data managers at the transplant centers who contributed data to the Japan Society for Hematopoietic Cell Transplantation, the Japan Marrow Donor Program, the Japan Cord Blood Bank Network, and the Japanese Society of Pediatric Hematology/Oncology.

Inherited Disease Working Group of the Japan Society for Hematopoietic Cell Transplantation

Katsutsugu Umeda, Hiromasa Yabe, Koji Kato, Kohsuke Imai, Nao Yoshida, Yoji Sasahara, Souichi Adachi, Tomohiro Morio.

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Authors and Affiliations

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

    Katsutsugu Umeda

  2. Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Japan

    Hiromasa Yabe

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

    Koji Kato & Nao Yoshida

  4. Department of Community Pediatrics, Perinatal and Maternal Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Kohsuke Imai & Tomohiro Morio

  5. Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

    Masao Kobayashi

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

    Yoshiyuki Takahashi

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

    Maho Sato & Masami Inoue

  8. Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan

    Yoji Sasahara

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

    Keisuke Kato

  10. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Souichi Adachi

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

    Yuhki Koga

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

    Keiko Okada

  13. Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan

    Yoshiko Hashii

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

    Yoshiko Atsuta

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  1. Katsutsugu Umeda
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on behalf of the Inherited Disease Working Group of the Japan Society for Hematopoietic Cell Transplantation

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Correspondence to Katsutsugu Umeda.

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Umeda, K., Yabe, H., Kato, K. et al. Impact of low-dose irradiation and in vivo T-cell depletion on hematopoietic stem cell transplantation for non-malignant diseases using fludarabine-based reduced-intensity conditioning. Bone Marrow Transplant 54, 1227–1236 (2019). https://doi.org/10.1038/s41409-018-0418-8

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