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Viral Infection

EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era

Bone Marrow Transplantation volume 49, pages 280–286 (2014)Cite this article

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Abstract

EBV-associated post-transplant lymphoproliferative disease (PTLD) following Alemtuzumab-based allo-SCT is a relatively uncommon and challenging clinical problem but has not received detailed study in a large cohort. Quantitative-PCR (qPCR) monitoring for EBV reactivation post allo-SCT is now commonplace but its diagnostic and predictive value remains unclear. Sixty-nine patients with PTLD following Alemtuzumab-based allo-SCT were studied. Marked clinicopathological heterogeneity was evident; lymphadenopathy was frequently absent, whereas advanced extranodal disease was common. The median viral load at clinical presentation was 49 300 copies/mL (50–65 200 000 copies/mL) and, notably, 23% and 45% of cases, respectively, had ⩽10 000 and ⩽40 000 copies/mL. The overall response rate to rituximab as first-line therapy was 70%. For rituximab failures, chemotherapy was ineffectual but DLIs were successful. A four-parameter prognostic index predicted response to therapy (OR 0.30 (0.12–0.74); P=0.009] and PTLD mortality (hazard ratio (HR) 1.81 (1.12–2.93) P=0.02) on multivariate analysis. This is the largest detailed series of EBV-associated PTLD after allo-SCT. At clinical presentation, EBV-qPCR values are frequently below customary thresholds for pre-emptive therapy, challenging current paradigms for monitoring and intervention. A four-point score identifies a proportion of patients at risk of rituximab-refractory disease for whom alternative therapy is needed.

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Acknowledgements

CPF received research funding from Leukaemia and Lymphoma Research, UK. DB received research funding from the Wellcome Trust UK.

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Authors and Affiliations

  1. Department of Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK

    C P Fox, C M Harvey & J L Byrne

  2. School of Cancer Sciences, University of Birmingham, Birmingham, UK

    C P Fox, D Burns, C F Craddock & S Chaganti

  3. University Hospitals Birmingham NHS Trust, Birmingham, UK

    D Burns, G Chakupurakal, C F Craddock & S Chaganti

  4. The Beatson, West of Scotland Cancer Centre, Glasgow, UK

    A N Parker

  5. University College London, Cancer Institute, London, UK

    K S Peggs & J A L Yin

  6. Manchester Royal Infirmary, Manchester, UK

    S Natarajan

  7. University Hospitals Bristol NHS Trust, Bristol, UK

    D I Marks

  8. The Royal Marsden, London, UK

    B Jackson & B E Shaw

  9. The Christie NHS Foundation Trust, Manchester, UK

    M Dennis

  10. King's College Hospital NHS Trust, London, UK

    Z Lim

  11. St James's Institute of Oncology, Leeds, UK

    G Cook

  12. Royal Free London NHS Trust, London, UK

    B Carpenter & R Chakraverty

  13. University of Liverpool, Liverpool, UK

    A R Pettitt

  14. The Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK

    S Mathew

  15. University Hospitals of Leicester NHS Trust, Leicester, UK

    L Connelly-Smith

  16. Cancer Research UK Clinical Trials Unit, University of Birmingham, UK

    M Viskaduraki & C Brookes

  17. University Hospital Southampton NHS Trust, Southampton, UK

    K Orchard

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Correspondence to C P Fox.

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Competing interests

CPF has received travel grants and speaker honoraria from Roche UK. ARP has received travel grants, advisory board and speaker honoraria from Roche UK. SC has received travel grants from Roche UK.

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Fox, C., Burns, D., Parker, A. et al. EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplant 49, 280–286 (2014). https://doi.org/10.1038/bmt.2013.170

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