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Post-transplant Events

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning

Bone Marrow Transplantation volume 49, pages 110–115 (2014)Cite this article

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Abstract

Graft rejection remains a major obstacle in allogeneic hematopoietic SCT following reduced-intensity conditioning (RIC-SCT), particularly after cord blood transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft rejection was associated with activation and expansion of donor-reactive host T cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells are at least partly involved in host T-cell activation. We then evaluated if such an expansion of host T cells could be associated with graft rejection after RIC-CBT. Expansion of residual host lymphocytes was observed in 4/7 patients with graft rejection at 3 weeks after CBT, but in none of the 17 patients who achieved engraftment. These results suggest the crucial role of residual host T cells after RIC-SCT in graft rejection and expansion of host T cells could be a marker of graft rejection. Development of more efficient T cell-suppressive conditioning regimens may be necessary in the context of RIC-SCT.

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Acknowledgements

We thank the patients and their families who participated in these clinical trials and the inpatient and outpatient bedside nurses who provided expert care on a daily basis to these patients at our institution. This study was supported by JSPS KAKENHI (25293217 to TT), and Health and Labor Science Research Grants (TT). We thank Dr Steven Lane and Dr Claudia Bruedigam, QIMR, for expert technical assistance with stem cell assays.

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Authors and Affiliations

  1. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan

    M Koyama, K Aoyama, T Miyamoto & K Akashi

  2. Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia

    M Koyama & G R Hill

  3. Department of Hematology, Hokkaido University Graduate School of Medical Science, Sapporo, Japan

    D Hashimoto & T Teshima

  4. Department of Hematology, Kurume University, Fukuoka, Japan

    K Nagafuji

  5. Department of Hematology, Hamanomachi General Hospital, Fukuoka, Japan

    T Eto

  6. Internal medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

    Y Ohno

  7. Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan

    H Iwasaki & K Akashi

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  1. M Koyama
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Correspondence to T Teshima.

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MK, DH, KA and YS performed the research; MK, KN, TE, YO and TM analyzed patient data; MK and TT designed the research study and wrote the paper.

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Koyama, M., Hashimoto, D., Nagafuji, K. et al. Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning. Bone Marrow Transplant 49, 110–115 (2014). https://doi.org/10.1038/bmt.2013.134

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