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Persistent recipient-derived human adenovirus (HAdV)

-specific T cells promote HAdV control after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 52, pages 609–611 (2017)Cite this article

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Patients after hematopoietic stem cell transplantation (HSCT) are at high risk for viral infections or reactivation. EBV, CMV, polyoma virus BK (BKV), human adenovirus (HAdV) and human herpesvirus 6 (HHV6) are the most common infections in transplanted patients. In pediatric patients, HAdV infection or reactivation is frequent due to persistence of HAdV in intestinal lymphoid cells and often associated with high morbidity and mortality.1, 2, 3 HAdV can cause localized (respiratory, hepatic or gastrointestinal infections, kerato-conjunctivitis) or disseminated disease in immunocompromised patients.2 The overall fatality rate can reach up to 50%.4 The virus is a non-enveloped, double-stranded DNA virus with over 70 serotypes divided into seven species (A–G). The viral capsid is composed of three major proteins: hexon, penton base and fiber.5 Viral clearance is usually achieved by a functional anti-HAdV T-cell response.6, 7 Depending on conditioning regimen, the use of T-cell depleting antibodies, in vitro T-cell depletion and donor HAdV status recovery of antiviral T-cell responses may be delayed for several weeks.4, 8, 9 Monitoring of HAdV load via PCR in blood and / or stool is recommended after HSCT to enable early or pre-emptive treatment.10, 11, 12 Currently, cidofovir is used as standard virostatic treatment.13 In addition, several publications demonstrate a therapeutic effect of adoptively transferred HAdV- or multivirus-specific T cells.14, 15, 16

In patients with CMV reactivation persistence of recipient-derived CMV-specific T cells mediating viral control has been reported mainly after non-myeloablative conditioning regimens.17 Here, we establish the platform to evaluate donor-/recipient provenience in virus-specific T cells and demonstrate persistence of recipient-derived HAdV-specific T cells in two pediatric patients after HSCT.

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Acknowledgements

This work was supported by the German children’s cancer fund (DKS 2011.05) and the German Federal Ministry of Education and Research (01EO1302). We thank Nicole Neumann, Dörthe Rokitta and Christopher Mielke for excellent technical assistance.

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Authors and Affiliations

  1. Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

    R E Schultze-Florey & B Maecker-Kolhoff

  2. Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany

    R E Schultze-Florey, S Tischer, B Eiz-Vesper & B Maecker-Kolhoff

  3. Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany

    S Tischer & B Eiz-Vesper

  4. Institute of Human Genetics, Hannover Medical School, Hannover, Germany

    W Kühnau

  5. Institute of Virology, Hannover Medical School, Hannover, Germany

    A Heim

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  1. R E Schultze-Florey
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  2. S Tischer
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  4. A Heim
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  6. B Maecker-Kolhoff
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Correspondence to B Maecker-Kolhoff.

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Schultze-Florey, R., Tischer, S., Kühnau, W. et al. Persistent recipient-derived human adenovirus (HAdV). Bone Marrow Transplant 52, 609–611 (2017). https://doi.org/10.1038/bmt.2016.321

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