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Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia

Bone Marrow Transplantation volume 54, pages 68–75 (2019)Cite this article

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Abstract

Graft-versus-host disease (GVHD) occasionally leads to morbidity and mortality but is thought to reduce the risk of relapses in patients with a hematological malignancy. However, information on the effect of GVHD in pediatric leukemia is limited. Using a nationwide registry, we retrospectively analyzed 1526 children who underwent allogeneic stem cell transplantation for leukemia. Grades 0–I acute GVHD were associated with a higher relapse rate at three years after transplantation, at 25.4 and 24.3%, respectively, than grades II, III, or IV acute GVHD at 18.9%, 21.2%, and 2.6%, respectively. In contrast, the overall survival curve of the grades 0 and I GVHD groups (79.0% and 79.5%, respectively) approximated that of the grade II GVHD group (76.3%), and the probability of survival was worst in the severe GVHD groups (66.9% for grade III and 42.5% for grade IV). Chronic GVHD also reduced the relapse risk but conferred no survival advantage. Acute lymphoblastic leukemia was more sensitive to acute GVHD than acute myeloid leukemia (AML) while AML was more sensitive to chronic GVHD. Our study reproduced the preventive effects of GVHD against pediatric leukemia relapses but failed to demonstrate a significant survival advantage.

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Acknowledgements

We thank all the staff at the participating hospitals and centers who provided valuable data from the JSHCT registry. A script kindly provided by Dr. Yoshinobu Kanda, Saitama Medical Center, Jichi Medical University, was used for data manipulation. 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 in part by a Research Grant for Allergic Disease and Immunology from the Japanese Ministry of Health, Labor, and Welfare, and the research grand from the National Center for Child Health and Development (27-4 and 28-5).

Authors contributions

MK is the principal investigator and takes principal responsibility for the paper. MK, JK, KK, DT, KK, NY, KW, HS, TT, MM, and YA designed the study. JI, KKo, MI, HG, KK, YC, YY, AO, JH, YH, and AY recruited the patients and collected the data. MK, MKu, and YA analyzed the data. MK and JK wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Authors and Affiliations

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

    Motohiro Kato & Daisuke Tomizawa

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

    Motohiro Kato

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

    Mio Kurata & Yoshiko Atsuta

  4. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Junya Kanda

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

    Koji Kato & Nao Yoshida

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

    Kazuko Kudo

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

    Kenichiro Watanabe

  8. Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan

    Hiroyuki Shimada

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

    Jiro Inagaki

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

    Katsuyoshi Koh

  11. Division of Hemato-oncology/Regenerative Medicine, Kanagawa Children’s Medical Center, Yokohama, Japan

    Hiroaki Goto

  12. Department of Hematology/Oncology, Ibaraki Children’s Hospital, Mito, Japan

    Keisuke Kato

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

    Yuko Cho

  14. Department of Hematology/Oncology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Yuki Yuza

  15. Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, Japan

    Atsushi Ogawa

  16. Department of Pediatric Hematology and Oncology, Osaka City General Hospital, Osaka, Japan

    Keiko Okada

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

    Masami Inoue

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

    Yoshiko Hashii

  19. Department of Hematology, Faculty of Medicine, Hokkaido University, Sapporo, Japan

    Takanori Teshima

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

    Makoto Murata

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

    Yoshiko Atsuta

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  1. Motohiro Kato
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  2. Mio Kurata
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  3. Junya Kanda
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  4. Koji Kato
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  13. Keisuke Kato
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  14. Yuko Cho
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  15. Yuki Yuza
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  16. Atsushi Ogawa
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  18. Masami Inoue
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  19. Yoshiko Hashii
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  21. Makoto Murata
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  22. Yoshiko Atsuta
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Correspondence to Motohiro Kato.

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Kato, M., Kurata, M., Kanda, J. et al. Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. Bone Marrow Transplant 54, 68–75 (2019). https://doi.org/10.1038/s41409-018-0221-6

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  • DOI: https://doi.org/10.1038/s41409-018-0221-6

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