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Impact of T-cell chimerism on relapse after cord blood transplantation for hematological malignancies: Nagoya Blood and Marrow Transplantation Group study

Bone Marrow Transplantation volume 52, pages 612–614 (2017)Cite this article

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Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for hematological malignancies. Cord blood is an alternative stem cell source when no suitable related or unrelated adult donor is available. Compared with other stem cell sources, cord blood stem cells allow HLA incompatibility from 0 to 2 locus mismatches of HLA -A, -B and -DR because their immune tolerance suppresses graft rejection and severe GvHD. Cord blood transplantation (CBT) is often adopted for high risk diseases due to its easy and rapid availability. Chimerism analysis of peripheral blood or bone marrow post HSCT is one of the strategies used to detect residual host hematopoiesis or leukemic cells. Chimerism analysis with PCR using specific short tandem repeats (STRs) of the recipient and donor can assess chimerism status even if there is no sex mismatch.1 Previous studies examined the relationships between chimerism post HSCT and prognosis.2, 3 The early detection of mixed chimerism may be a predictive factor for relapse. In the present study, a lineage-specific chimerism analysis using STRs was performed at each time point post CBT. Since allo-reactive T cells have a crucial role in the suppression of relapse post HSCT, we focused on the relationship between T-cell chimerism and relapse.

Data were obtained from six adult transplant centers affiliated with the Nagoya Blood and Marrow Transplantation Group. Patients who underwent allogeneic stem cell transplantation were enrolled in this prospective study to monitor the post-transplant chimerism status. In addition to basic clinical information prospectively collected for the chimerism analysis, patient-, disease- and transplant-related data as well as transplant outcome data were collected. Among those who were enrolled in this chimerism study, 78 patients who received cord blood transplantation (CBT) as the first hematopoietic stem cell transplantation (HSCT) for hematological malignancies between 2005 and 2012 were included. The Institutional Review Board of the Nagoya University Graduate School of Medicine approved this retrospective analysis. The post-transplant chimerism status of peripheral blood cells was assessed by STR analysis as previously described.4, 5 Cord blood cells were collected from residual cells in the bag on day 0. The heparinized peripheral blood samples of the recipients were collected before, and at days 14, 28, 56 and 84 (+/− 7 days) after the transplant. Granulocytes were obtained from precipitate by removing lysed cells after incubation in ammonium chloride buffer. MNCs were separated into three fractions using immunomagnetic beads; the CD56+ fraction (called the natural killer (NK) cell fraction), the CD56−/CD3+ fraction (called the T-cell fraction), and the CD56−/CD3- fraction (called the other MNC fraction). Post-transplant donor-type chimerism of⩾95% was defined as complete donor chimerism (CDC) and <95% as mixed chimerism (MC). The primary end point was relapse after transplant according to the post-transplant chimerism status at days 28, 56 and 84. For analysis of cumulative incidence of relapse, cases that relapsed or died before the time points of chimerism analysis and cases with missing data were excluded from the analysis. Secondary end points were treatment-related mortality, overall survival (OS), the incidence of grades II–IV and grades III–IV acute GvHD and chronic GvHD.

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Acknowledgements

We thank the transplantation team at the participating institutions for their contributions. This study was funded in part by JSPS KAKENHI Grant Number 26860346 from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Hematology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan

    E Yokohata, N Kawashima, A Seto, S Kurahashi, Y Ozawa & K Miyamura

  2. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan

    Y Kuwatsuka

  3. Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    H Ohashi, H Iida & T Naoe

  4. Division of Hematology, Toyota Memorial Hospital, Toyota, Japan

    H Ohashi

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

    S Terakura, A Seto, T Goto, N Imahashi, T Nishida, H Kiyoi, T Naoe & M Murata

  6. Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan

    K Miyao, R Sakemura, T Kato & M Sawa

  7. Department of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan

    A Kohno

  8. Department of Hematology, Meitetsu Hospital, Nagoya, Japan

    H Sao

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  1. E Yokohata
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for the Nagoya Blood and Marrow Transplantation Group

Corresponding author

Correspondence to Y Kuwatsuka.

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Competing interests

HK received research funding from Chugai Pharmaceutical Co. Ltd., Bristol-Myers Squibb, Kyowa Hakko Kirin Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Zenyaku Kogyo Co. Ltd., FUJIFILM Corporation, Nippon Boehringer Ingelheim Co. Ltd. The remaining authors declare no conflict of interest.

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Yokohata, E., Kuwatsuka, Y., Ohashi, H. et al. Impact of T-cell chimerism on relapse after cord blood transplantation for hematological malignancies: Nagoya Blood and Marrow Transplantation Group study. Bone Marrow Transplant 52, 612–614 (2017). https://doi.org/10.1038/bmt.2016.323

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