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Impact of antithymocyte globulin usage and risk stratification for posttransplant lymphoproliferative disorders in aplastic anemia patients after allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation (2024)Cite this article

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Posttransplant lymphoproliferative disorders (PTLD) are severe complications of allogeneic hematopoietic cell transplantation (allo-HCT), often arising from EB virus (EBV)-infected lymphocytes due to posttransplant immunosuppression. [1] Key risk factors include ex vivo or in vivo T-cell depletion, including anti-thymocyte globulin (ATG) use, and unrelated or human leukocyte antigen (HLA)-mismatched donors. [2,3,4,5,6,7,8] Other varying risk factors among studies include graft-versus-host disease (GVHD), [2,3,4,5, 9] cord blood transplantation (CBT), [2] EBV seromismatch status, [5,6,7] recipient age, [4] conditioning intensity, [5] second transplantation, [2, 4] and a history of splenectomy. [5] A retrospective study using Japanese transplant registry data identified risk factors for PTLD in various hematological diseases, including aplastic anemia (AA), ATG administration in conditioning regimens, a history of ATG treatment for acute GVHD, transplantation from donors other than HLA-matched related donors, second or subsequent transplants, and CBT. [2] A single-center study involving 89 AA patients who underwent allo-HCT from bone marrow or peripheral blood donors reported that the total number of prior courses of ATG in immunosuppressive therapy (IST) strongly influenced the high incidence of EBV-related PTLD. [10] To further evaluate the risk factors, including donor source, conditioning type, and ATG dosage, for PTLD development in adult AA patients, we conducted a nationwide multicenter retrospective analysis using Japanese transplant registry data. Patients and Methods are described in Supplementary Information.

A total of 1071 patients, aged 16–75 years (median, 34 years), who underwent allo-HCT for AA were investigated. The median follow-up time for survivors was 5.2 years (range, 0.17–16.4 years). The baseline characteristics are summarized in Supplementary Table 1. Regarding the donor type, 463 patients (43%) received allo-HCT from a related donor including 54 patients (5%) from a haploidentical related donor, 432 (40%) from an unrelated donor, and 167 (16%) from cord blood (CB). Patients were classified into four groups based on their ATG usage history: patients who exclusively received ATG for IST (IST-only), patients who exclusively received ATG for conditioning regimens (Conditioning-only), patients who received ATG for both IST and conditioning regimens (Both-use), and patients who did not receive ATG (Non-use). Then, 145 (14%), 281 (26%), 261 (24%), and 374 (35%) patients were categorized into the Non-use, IST-only, Conditioning-only, and Both-use groups, respectively.

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Fig. 1: Cumulative incidence of posttransplant lymphoproliferative disorders (PTLD) and Overall survival.

Data availability

The data from the analyses reported in this study are available upon reasonable request from the corresponding authors.

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Acknowledgements

The authors thank all physicians and staff at the centers who provided clinical data to TRUMP. We would like to thank Editage (www.editage.jp) for English language editing.

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Authors and Affiliations

  1. Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan

    Ryusuke Yamamoto, Nobuhiro Hiramoto & Masashi Nishikubo

  2. Department of Hematology, Shimane University Hospital, Izumo, Japan

    Ayumi Fujimoto

  3. Division of Transfusion Medicine, Kanazawa University Hospital, Kanazawa, Japan

    Hirohito Yamazaki

  4. Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan

    Takehiko Mori

  5. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida

  6. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Noriko Doki

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

    Jun Kato

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

    Shinichi Kako

  9. Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan

    Tetsuya Nishida

  10. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Shuichi Ota

  11. Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan

    Makoto Onizuka

  12. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Tetsuya Eto

  13. Department of Hematology, Tohoku University Hospital, Sendai, Japan

    Koichi Onodera & Yasushi Onishi

  14. Department of Hematology, Hyogo Medical University Hospital, Hyogo, Japan

    Kazuhiro Ikegame

  15. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan

    Ken-ichi Matsuoka

  16. Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan

    Yoshinobu Kanda

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

    Takahiro Fukuda

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

    Yoshiko Atsuta

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

    Yoshiko Atsuta

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  1. Ryusuke Yamamoto
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  21. Yasushi Onishi
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Contributions

RY analyzed the data, performed statistical analysis, and wrote the manuscript. NH designed the study and revised the manuscript. AF, HY, and TM provided feedback for data analysis. YO provided feedback for data analysis and supervised the research. NU, ND, JK, MN, SK, TN, SO, MO, TE, KO, KI, KM, YK, TF, and YA contributed to the data collection. All the authors approved the final manuscript.

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Correspondence to Nobuhiro Hiramoto.

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Yamamoto, R., Hiramoto, N., Fujimoto, A. et al. Impact of antithymocyte globulin usage and risk stratification for posttransplant lymphoproliferative disorders in aplastic anemia patients after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02234-1

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