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Comparison of immunosuppressant regimens in salvage cord blood transplantation for graft failure after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 56, pages 400–410 (2021)Cite this article

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Abstract

Graft failure (GF) is a life-threatening complication after allogeneic stem cell transplantation. Although salvage cord blood transplantation (CBT) is a curative therapy for GF, the optimal immunosuppression after salvage CBT remains unknown. Using nationwide registration data, we compared the transplant outcomes of patients who developed GF and underwent salvage CBT using immunosuppressants, including calcineurin (CNI) alone (n = 177); CNI plus methotrexate (CNI+MTX, n = 150); and CNI plus mycophenolate mofetil (CNI+MMF, n = 161). The CNI+MMF group, in comparison with the CNI+MTX and CNI alone groups, demonstrated better neutrophil recovery at 30 days (62.7 vs. 42.7 vs. 53.1%, P < 0.001); better overall survival (OS) at 12 months (48.4 vs. 33.5 vs. 28.3%, P < 0.001); and lower non-relapse mortality (NRM) at 12 months (35.2 vs. 53.9 vs. 56.5%, P < 0.001). On multivariate analysis, CNI+MMF had the best neutrophil recovery (hazard ratio (HR), 1.71; P < 0.001) and OS (HR, 0.64; P = 0.002) and the lowest NRM (HR, 0.53; P < 0.001). Hemorrhage was relatively less frequent in the CNI+MMF group. CNI+MMF can be a promising immunosuppressant regimen after salvage CBT for GF, with better engraftment and survival outcomes, compared with CNI alone and CNI+MTX.

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Fig. 1: Cumulative incidence of hematologic recoveries after salvage transplantation according to the immunosuppressants.
Fig. 2: Survival rates after salvage transplantation according to the graft-vs.-host disease prophylaxis.
Fig. 3: Cumulative incidence of each extent of GVHD after salvage transplantation, according to the prophylaxis.
Fig. 4: Subgroup analyses for transplant outcomes according to the immunosuppressants in patients who received antithymocyte or antilymphocyte globulin.

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Acknowledgements

We thank all the physicians and staff at the transplant centers who provided the clinical data to the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation. This work 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 18ek0510023h0002.

Transplant Complications Working Group of the Japan Society for Hematopoietic Cell Transplantation

Kaito Harada1, Shigeo Fuji2, Sachiko Seo3, Makoto Onizuka1, Hideki Nakasone17

GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation

Naoyuki Uchida4, Shingo Yano6, Sachiko Seo3, Hideki Nakasone17, Seitaro Terakura16

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Authors and Affiliations

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

    Kaito Harada & Makoto Onizuka

  2. Department of Hematology, Osaka International Cancer Institute, Osaka, Japan

    Shigeo Fuji

  3. Department of Hematology and Oncology, Dokkyo Medical University School of Medicine, Mibu, Japan

    Sachiko Seo

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

    Naoyuki Uchida

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

    Toshiro Kawakita

  6. Clinical Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan

    Shingo Yano

  7. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Yukiyasu Ozawa

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

    Satoshi Yoshioka

  9. Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan

    Yasushi Onishi

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

    Yuma Noguchi

  11. Department of Hematology, Kawasaki Medical School Hospital, Kurashiki, Japan

    Yoshiko Matsuhashi

  12. Preparation Department, Japanese Red Cross Kinki Block Blood Center, Ibaraki, Japan

    Takafumi Kimura

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

    Tatsuo Ichinohe

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

    Yoshiko Atsuta

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

    Yoshiko Atsuta

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

    Seitaro Terakura

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

    Hideki Nakasone

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Harada, K., Fuji, S., Seo, S. et al. Comparison of immunosuppressant regimens in salvage cord blood transplantation for graft failure after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 56, 400–410 (2021). https://doi.org/10.1038/s41409-020-00999-9

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