Biology of Blood and Marrow Transplantation
Volume 14, Issue 6 , Pages 693-701, June 2008

Recipient-Derived Cells after Cord Blood Transplantation: Dynamics Elucidated by Multicolor FACS, Reflecting Graft Failure and Relapse

  • Nobukazu Watanabe

      Affiliations

    • FACS Core Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • Corresponding Author InformationCorrespondence and reprint requests: Nobukazu Watanabe, MD, PhD, FACS Core Laboratory, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
    • The first two authors contributed equally to this work.
    • ,
  • Satoshi Takahashi

      Affiliations

    • Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • The first two authors contributed equally to this work.
    • ,
  • Masayuki Ishige

      Affiliations

    • FACS Core Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • ,
  • Yumiko Ishii

      Affiliations

    • FACS Core Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • ,
  • Jun Ooi

      Affiliations

    • Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • ,
  • Akira Tomonari

      Affiliations

    • Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • ,
  • Nobuhiro Tsukada

      Affiliations

    • Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • ,
  • Takaaki Konuma

      Affiliations

    • Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • ,
  • Seiko Kato

      Affiliations

    • Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • ,
  • Aki Sato

      Affiliations

    • Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • ,
  • Arinobu Tojo

      Affiliations

    • Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    • ,
  • Hiromitsu Nakauchi

      Affiliations

    • Center for Stem Cell and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Received 20 February 2008; accepted 7 April 2008.

Abstract 

Although umbilical cord blood has been increasingly used as an alternative donor source to treat hematologic malignancies, cord blood transplantation (CBT) is frequently complicated by graft failure and relapse of primary diseases. Because persistence or increase of recipient-derived hematopoietic or malignant cells has pathogenic import under these conditions, analysis of recipient-derived cells should be useful to understand the pathogenesis of graft failure and relapse of primary disease. Because most CBT involves human leukocyte antigen (HLA)-mismatched transplantation, we developed a 9-color fluorescence activated cell sorter (FACS)-based method of mixed chimerism (MC) analysis using anti-HLA antibodies to detect mismatched antigens (HLA-Flow method). Among CD4+ T cells, CD8+ T cells, B cells, NK cells, monocytes, and granulocytes, donor- and recipient-derived cells alike could be individually analyzed simultaneously in a rapid, quantitative and highly sensitive manner, making the HLA-Flow method very valuable in monitoring the engraftment process. In addition, this method was also useful in monitoring recipient-derived cells with leukemia-specific phenotypes, both as minimal residual disease (MRD) and as early harbingers of relapse. Leukemia relapse can be definitively diagnosed by cytogenetic or PCR studies using recipient-derived cells sorted for leukemia markers. Multicolor HLA-fFlow analysis and cell sorting in early diagnosis of graft failure and relapse was confirmed as valuable in 14 patients who had received HLA-mismatched CBT.

Key Words: Chimerism, HLA, Flow cytometry, Cord blood transportation

 

PII: S1083-8791(08)00145-6

doi:10.1016/j.bbmt.2008.04.001

Biology of Blood and Marrow Transplantation
Volume 14, Issue 6 , Pages 693-701, June 2008

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