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Management of Adenovirus in Children after Allogeneic Hematopoietic Stem Cell Transplantation

DOI: 10.1155/2013/176418

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Abstract:

Adenovirus (ADV) can cause significant morbidity and mortality in children following haematopoietic stem cell transplantation (HSCT), with an incidence of up to 27% and notable associated morbidity and mortality. T-cell depleted grafts and severe lymphopenia are major risk factors for the development of adenovirus disease after HSCT. Current antiviral treatments are at best virostatic and may have significant side effects. Adoptive transfer of donor-derived virus-specific T cells has been shown to be an effective strategy for the prevention and treatment of ADV infection after HSCT. Here we review progress in the field and present a pathway for the management of adenovirus in the posttransplant setting. 1. Introduction Adenovirus (ADV) causes mild illnesses in immunocompetent hosts but can cause significant morbidity and mortality in the immunocompromised, for example, children in the posthaematopoietic stem cell transplant setting. Haematopoietic stem cell transplantation (HSCT) can offer a cure for many haematological diseases, primary immunodeficiencies, and inborn errors of metabolism. However, not all transplant recipients have fully matched sibling donors and alternative donor sources have to be sought. In HLA-matched or mismatched unrelated donor setting, conditioning regimens will often include serotherapy such as Alemtuzumab (monoclonal anti-CD52 antibody) or thymoglobulin (polyclonal horse or rabbit thymocyte globulin [ATG]) to remove alloreactive T cells in the recipient that can cause acute Graft versus Host Disease (GVHD). During the posttransplant period of reduced T-cell immunity when reconstitution of donor-derived immune system is slow and the use of immunosuppressive agents is necessary, transplant recipients are especially vulnerable to viral reactivations and/or infections. Whilst antivirals such as ribavirin and cidofovir are available for the treatment of ADV, they are associated with toxicity and have variable efficacy. Over the past decade or so, adoptive transfer of donor-derived virus-specific T cells has been explored extensively as an alternative method to prevent and treat ADV and other viral infections after HSCT. This review examines recent preclinical and clinical studies on T-cell immunotherapy for ADV and provides a strategy for monitoring and management of ADV in children after allo-HSCT. 2. Adenovirus Adenoviruses (ADV) were first isolated in 1953 from human adenoid tissues obtained during adenoidectomy [1]. They are nonenveloped, double stranded DNA viruses that range in size from 65 to 80?nm in diameter [2]. To

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