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Effect of the order of TBI and cyclophosphamide administration on the outcome of allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 50, pages 1476–1479 (2015)Cite this article

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TBI combined with cyclophosphamide (CY) is among the most common myeloablative conditioning regimens used in conjunction with allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of various hematological malignancies.1, 2 In a mouse model of transplantation, donor lymphocyte infusion immediately after TBI was associated with a significantly higher incidence of acute GvHD when compared with delayed donor lymphocyte infusion after TBI,3 a finding that might be explained by differences in the levels of inflammatory cytokines induced by TBI at the time of donor cell infusion. Specifically, the cytokine levels should have been higher in animals treated with TBI immediately before donor cell infusion, and the cytokines would thus have contributed more significantly to donor T-cell activation.4, 5, 6 In pediatric patients subjected to conditioning regimens for allogeneic HSCT, the administration of TBI before high-dose chemotherapy has been reported to lead to an increased risk of acute GvHD.7 However, it remains unclear whether the order of TBI and CY administration affects transplant-associated complications and transplant outcomes in adults. The purpose of this study was to clarify the effect of the order of TBI and CY administration on the outcome of allogeneic HSCT.

We retrospectively investigated the transplant outcomes of consecutive patients with AML, ALL and myelodysplastic syndrome (MDS) who underwent initial allogeneic HSCT with myeloablative conditioning regimens comprising TBI and CY between 1 January 2001 and 31 August 2012 at 20 institutes in Japan participating in the Kanto Study Group for Cell Therapy. Although patients who received cord blood units were included regardless of the degree of HLA disparity, 126 patients who received HLA-mismatched grafts from related or unrelated donors were excluded. Patients who received conditioning agents such as cytarabine, thiotepa and etoposide in addition to CY and TBI and those subjected to ex vivo or in vivo T-cell depletion were excluded. This study was approved by the institutional review board of Yokohama City University Medical Center. The trial was conducted in accordance with the Declaration of Helsinki.

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Acknowledgements

The authors thank the members of the Kanto Study Group for Cell Therapy.

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Authors and Affiliations

  1. Department of Hematology, Yokohama City University Medical Center, Yokohama, Japan

    K Motohashi & S Fujisawa

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

    M Onizuka

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

    S Kako

  4. Division of Hematology, Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan

    E Sakaida

  5. Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba, Japan

    K Shono

  6. Division of Hematology, Jichi Medical University, Shimotsuke, Japan

    R Tatara

  7. Division of Hematology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan

    N Doki

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

    T Mori & S Okamoto

  9. Leukemia Research Center, Gunmaken Saiseikai Maebashi Hospital, Maebashi, Japan

    T Sakura

  10. Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, Narita, Japan

    N Aotsuka

  11. Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan

    E Fuji & H Kanamori

  12. Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    N Tomita

  13. Department of Hemato-Oncology, Saitama International Medical Center, Saitama Medical University, Saitama, Japan

    N Kawai

  14. Department of Hematology, Gunma University Hospital, Maebashi, Japan

    T Saitoh

  15. Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan

    K Usuki

  16. Department of Hematology, Shizuoka Red Cross Hospital, Shizuoka, Japan

    J Taguchi

  17. Department of Hematology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    R Watanabe

  18. Department of Hematology, Nihon University Itabashi Hospital, Tokyo, Japan

    S Kobayashi

  19. Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    S Yano

  20. Department of Hematology and Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    S Takahashi

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  1. K Motohashi
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  2. S Fujisawa
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  3. M Onizuka
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  21. H Kanamori
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for the Kanto Study Group for Cell Therapy (KSGCT)

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Correspondence to K Motohashi.

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Motohashi, K., Fujisawa, S., Onizuka, M. et al. Effect of the order of TBI and cyclophosphamide administration on the outcome of allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 50, 1476–1479 (2015). https://doi.org/10.1038/bmt.2015.142

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