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Review
. 2014 Nov;21(6):476-81.
doi: 10.1097/MOH.0000000000000083.

Epstein-Barr virus lymphoproliferative disease after hematopoietic stem cell transplant

Rayne H Rouce  1 , Chrystal U Louis, Helen E Heslop
Affiliations
Review

Epstein-Barr virus lymphoproliferative disease after hematopoietic stem cell transplant

Rayne H Rouce et al. Curr Opin Hematol. 2014 Nov.

Abstract

Purpose of review: Epstein-Barr virus (EBV) reactivation can cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplant. Delays in reconstitution of EBV-specific T lymphocyte activity can lead to life-threatening EBV lymphoproliferative disease (EBV-PTLD). This review highlights recent advances in the understanding of pathophysiology, risk factors, diagnosis, and management of EBV viremia and PTLD.

Recent findings: During the past decade, early detection strategies, such as serial measurement of EBV-DNA load, have helped identify high-risk patients and diagnose early lymphoproliferation. The most significant advances have come in the form of innovative treatment options, including manipulation of the balance between outgrowing EBV-infected B cells and the EBV cytotoxic T lymphocyte response, and targeting infected B cells with monoclonal antibodies, chemotherapy, unmanipulated donor lymphocytes, and donor or more recently third-party EBV cytotoxic T lymphocytes. Defining criteria for preemptive therapy remains a challenge.

Summary: EBV reactivation is a significant complication after stem cell transplant. Continued improvements in risk stratification and treatment options are required to improve the morbidity and mortality caused by EBV-associated diseases. Current approaches use rituximab to deplete B cells or adoptive transfer of EBV cytotoxic T lymphocyte to reconstitute immunity. The availability of rapid EBV-specific T cell products offers the possibility of improved outcomes.

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References

    1. Heslop HE. How I treat EBV lymphoproliferation. Blood. 2009 Nov 5;19(114):4002–4008. - PMC - PubMed
    1. Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med. 2005;(56):29–44. - PubMed
    1. Aalto SM, Juvonen E, Tarkkanen J, et al. Lymphoproliferative disease after allogeneic stem cell transplantation--pre-emptive diagnosis by quantification of Epstein-Barr virus DNA in serum. J Clin Virol. 2003 Dec;3(28):275–283. - PubMed

    1. Uhlin M, Wikell H, Sundin M, et al. Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation. Haematologica. 2014 Feb;2(99):346–352. In a large cohort of patients, the authors identified HLA mismatch, serological EBV mismatch, RIC, acute GVHD, pre-transplant splenectomy, and infusion of mesenchymal stromal cells as significant risk factors for development of EBV-PTLD.

    1. Liu Q, Xuan L, Liu H, et al. Molecular monitoring and stepwise preemptive therapy for Epstein-Barr virus viremia after allogeneic stem cell transplantation. Am J Hematol. 2013 Jul;7(88):550–555. The authors employed a preemptive intervention protocol based on duration and changes in EBV viral load. They concluded that more frequent monitoring of EBV-DNA and earlier preemptive rituximab should be advocated in patients at high-risk of developing EBV-PTLD.

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