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Clinical course of autologous recovery with chromosomal abnormalities after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 1023–1028 (2020)Cite this article

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Abstract

After primary graft failure following allogeneic hematopoietic stem cell transplantation, some patients experience autologous recovery of hematopoiesis without salvage transplantation. However, clinicians occasionally encounter unusual chromosomal abnormalities in recipient cells, not related to the original underlying diseases. In this study, through a survey based on data from the nationwide registry at the Japan Society for Hematopoietic Cell Transplantation, 42 patients were identified as having chromosomal abnormalities after autologous recovery. The complex chromosomal abnormalities were not consistent and randomly changed at each testing. Of the 42 patients, seven experienced disappearance of chromosome abnormalities without any treatment, and the probability was estimated as 17.4% (95% CI: 7.5–30.7%) at the 5-year observation. On the other hand, two patients developed hematologic malignancy at 1447 and 6202 days. Ten patients were alive without relapse or development of hematologic disorders, even though chromosomal abnormalities were continuously detected at a median of 3192 (103–4710) days. In conclusion, chromosomal abnormalities can persist for more than 10 years, and may eventually contribute to hematologic malignancy development in a small fraction of cases. Although oncogenic effects of the chromosomal abnormalities are still unclear, these findings may provide supporting evidence for late occurrence of secondary malignant neoplasms after cancer treatment.

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Fig. 1: Clinical course of chromosomal abnormalities after autologous recovery.
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Acknowledgements

We would like to thank all the staff at the hospitals and centers who provided precise data via the registry at the JSHCT. A script kindly provided by Dr. Yoshinobu Kanda, Saitama Medical Center, Jichi Medical University, was used for data manipulation. We also thank the medical editors from the Department of Education for Clinical Research at the National Center for Child Health and Development for their assistance in editing this manuscript, and thank Ms. Etsuko Mochizuki for technical assistance. 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 a research grant from the National Center for Child Health and Development (28-5B).

Author contributors

MK is the principal investigator and takes primary responsibility for the paper. MK, HN, NN, SF, AS, and MO designed the research; HY, KS, TH, ST, MN, YK, TM, JT, HK, TK, TI, TF, and YA recruited the patients and collected the data. All authors critically reviewed the manuscript and agreed to submit the paper for publication.

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Authors and Affiliations

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

    Motohiro Kato

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

    Motohiro Kato

  3. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Hideki Nakasone & Yoshinobu Kanda

  4. Department of Hematology, Imamura General Hospital, Kagoshima, Japan

    Nobuaki Nakano

  5. Department of Hematology, Osaka International Cancer Center, Osaka, Japan

    Shigeo Fuji

  6. Department of Hematology, Tokyo Women’s Medical University, Tokyo, Japan

    Akihito Shinohara

  7. Department of Hematology, National Hospital Organization Sendai Medical Center, Sendai, Japan

    Hisayuki Yokoyama

  8. Department of Hematology/Oncology, Nagano Children’s Hospital, Nagano, Japan

    Kazuo Sakashita

  9. Department of Pediatrics, Sapporo Medical University Hospital, Sapporo, Japan

    Tsukasa Hori

  10. Division of Molecular Therapy, the Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan

    Satoshi Takahashi

  11. Division of Hematology, Nephrology and Rheumatology, Akita University Hospital, Akita, Japan

    Miho Nara

  12. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Takehiko Mori

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

    Junko Takita

  14. Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan

    Hiroshi Kawaguchi

  15. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

    Toshiro Kawakita

  16. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima, Japan

    Tatsuo Ichinohe

  17. Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

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

    Yoshiko Atsuta

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

    Yoshiko Atsuta

  20. Department of Hematology, Oita University Hospital, Oita, Japan

    Masao Ogata

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  1. Motohiro Kato
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on behalf of Transplantation Complication Working Group of the Japan Society for Hematopoietic Cell Transplantation

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Correspondence to Motohiro Kato.

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Conflict of interest

MK received research funding from Daiichi Sankyo. TM received research funding from MSD, Novartis Pharma, LSI Medience, Medical & Biological Laboratories, and Asahi Kasei Corporation, and personal fees from Pfizer Inc., MSD, Janssen Pharma, Sumitomo Dainippon Pharma, Novartis Pharma, Kyowa Kirin, Chugai Pharmaceutical, Shionogi & Co., Japan Blood Products Organization, Takeda Pharmaceutical, Ono Pharmaceutical, Shire, Eisai, and Astellas Pharma. The remaining authors declare no competing financial interests.

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Kato, M., Nakasone, H., Nakano, N. et al. Clinical course of autologous recovery with chromosomal abnormalities after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 55, 1023–1028 (2020). https://doi.org/10.1038/s41409-019-0765-0

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