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


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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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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Correspondence to Kaito Harada.

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Members of the Transplant Complications Working Group of the Japan Society for Hematopoietic Cell Transplantation and GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation are listed below Acknowledgements

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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 (2020).

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