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Early detection of cytomegalovirus-specific cytotoxic T lymphocytes against cytomegalovirus antigenemia in human leukocyte antigen haploidentical hematopoietic stem cell transplantation

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Abstract

Human leukocyte antigen (HLA)-haploidentical stem cell transplantation (haplo-SCT) is associated with a high incidence of cytomegalovirus (CMV) infection, probably originating from the delayed reconstitution of CMV-specific T cell immunity. There have been few reports on the presence of CMV-specific cytotoxic T lymphocytes (CMV-CTLs) after haplo-SCT. We have studied CMV-specific immune reconstitution by measuring the absolute number of CMV-CTLs using a flow cytometry method with HLA-A2-restricted NLVPMVATV peptide dextramers. We examined the association between reconstitution patterns of CMV-CTLs and the duration of CMV antigenemia in 15 patients who underwent first allogeneic SCT from HLA-haploidentical-related donors with HLA-A2. In seven and eight patients, CMV antigenemia consecutively resolved for more than 4 weeks (the CMV antigenemia ‘resolved’ group) and intermittently persisted (the CMV antigenemia ‘persistent’ group) during a 100-day observation period, respectively. The group of the seven patients, in whom levels of CMV antigenemia were reduced to zero, had a significantly lower maximum level of CMV antigenemia than the CMV antigenemia persistent group. In contrast, the CMV antigenemia persistent group had a significantly higher maximum level of CMV-CTLs, but the levels took longer to peak. Despite no difference in general lymphocyte recovery between the two groups, the CMV antigenemia resolved group had significantly higher median CMV-CTL counts than the CMV antigenemia persistent group at 6 weeks after onset of CMV infection. Flow cytometry analysis of CMV-CTLs is a convenient method of monitoring reconstitution of CMV-specific lymphocyte immunity following haplo-SCT.

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Acknowledgments

We thank the medical staff of the Hyogo College of Medicine Hospital, Japan, for medical attendance during patient follow-up. We also thank Ms. Kimiko Yamamoto for technical assistance.

Conflict of interest

The authors have no potential conflict of interests.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya City, Hyogo, 663-8501, Japan

    Ruri Kato, Hiroya Tamaki, Kazuhiro Ikegame, Satoshi Yoshihara, Katsuji Kaida, Kyoko Taniguchi, Takayuki Inoue, Shinichi Ishii, Jun Nakata, Tatsuya Fujioka, Toshihiro Soma, Masaya Okada & Hiroyasu Ogawa

  2. Laboratory of Cell Transplantation, Hyogo College of Medicine, Institute for Advanced Medical Science, Nishinomiya, Hyogo, Japan

    Hiroya Tamaki, Ryoji Eguchi, Toshihiro Soma & Hiroyasu Ogawa

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  1. Ruri Kato
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  2. Hiroya Tamaki
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  3. Kazuhiro Ikegame
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  14. Hiroyasu Ogawa
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Correspondence to Ruri Kato.

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Kato, R., Tamaki, H., Ikegame, K. et al. Early detection of cytomegalovirus-specific cytotoxic T lymphocytes against cytomegalovirus antigenemia in human leukocyte antigen haploidentical hematopoietic stem cell transplantation. Ann Hematol 94, 1707–1715 (2015). https://doi.org/10.1007/s00277-015-2446-4

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  • DOI: https://doi.org/10.1007/s00277-015-2446-4

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