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Microbial Issues

Impact of viral reactivations in the era of pre-emptive antiviral drug therapy following allogeneic haematopoietic SCT in paediatric recipients

Bone Marrow Transplantation volume 48, pages 803–808 (2013)Cite this article

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Abstract

While pre-emptive rituximab therapy for EBV has substantially reduced the incidence of post-transplant lymphoproliferative disorder, following allogeneic haematopoietic SCT (HSCT), cytomegalovirus (CMV) and adenovirus (ADV) still contribute to significant morbidity and mortality after HSCT. We therefore aimed to identify high-risk children who could benefit from recent advances in virus-specific immunotherapy, define the impact of viral reactivations on survival and estimate the economic burden of pre-emptive antiviral drug therapy. Between 2005 and 2010, prospective monitoring of 291 paediatric HSCT procedures revealed that reactivation of CMV (16%), ADV (15%) and EBV (11%) was frequent during period of CD4 T-cell lymphopenia (⩽0.15 × 109 L−1; P<0.05). We report significant risk factors for reactivation, most notably the use of serotherapy and development of GVHD (⩾grade II) in the presence of pre-existing infection (ADV) or donor and/or recipient seropositivity (CMV, EBV). Most interestingly, CMV and ADV viraemia were the major independent predictors of mortality (P<0.05). CMV, ADV or EBV viral reactivation caused prolonged hospitalization (P<0.05), accounted for 15% of all mortality and substantially increased the cost of transplantation by ∼£22 500 ($34 000). This provides an economic rationale for targeting high-risk HSCT recipients with interventions such as virus-specific cell therapy.

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Acknowledgements

We thank specialist nursing staff for the collection of blood samples and Fredrik Hanson from Commitum AB for statistical support. This work was supported by the Leukaemia and Lymphoma Research, Rowntree Trust, Great Ormond Street Hospital Children’s Charity with R&D funding from the UK Department of Health. Funding from the Technology Strategy Board was obtained jointly with CellMedica Ltd. The Technology Strategy Board is a business-led executive non-departmental public body, established by the government. Its role is to promote and support research into, and development and exploitation of, technology and innovation for the benefit of UK business, in order to increase economic growth and improve the quality of life. It is sponsored by the Department for Business, Innovation and Skills (BIS).

Author Contributions: PH undertook research, analyzed the data and wrote the manuscript; KG, CC, MJ undertook research; NBR, JB, HBG, RC, KR, NG, PA, GD and PV designed and undertook research; WQ designed research and wrote the paper.

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Authors and Affiliations

  1. Molecular Immunology Unit, Institute of Child Health, London, UK

    P Hiwarkar, H B Gaspar, K Gilmour & W Qasim

  2. Bone marrow and Blood Stem cell transplant unit, Great Ormond Street Hospital, London, UK

    P Hiwarkar, R Chiesa, N Bennett-Rees, K Rao, N Goulden, P Amrolia & P Veys

  3. Department of Pharmacy, Great Ormond Street Hospital, London, UK

    M Jagani

  4. Department of Virology, Great Ormond Street Hospital, London, UK

    J Breuer

  5. Department of Immunology, Great Ormond Street Hospital, London, UK

    C Cale, G Davies & W Qasim

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  1. P Hiwarkar
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Correspondence to P Hiwarkar.

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CellMedica is developing cell-based therapies to treat viral reactivation after HSCT.

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Hiwarkar, P., Gaspar, H., Gilmour, K. et al. Impact of viral reactivations in the era of pre-emptive antiviral drug therapy following allogeneic haematopoietic SCT in paediatric recipients. Bone Marrow Transplant 48, 803–808 (2013). https://doi.org/10.1038/bmt.2012.221

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