How I treat EBV lymphoproliferation

Abstract

Epstein-Barr virus (EBV)-associated B-cell lymphoproliferation is a life-threatening complication after hematopoietic stem cell or solid organ transplantation resulting from outgrowth of EBV-infected B cells that would normally be controlled by EBV-cytotoxic T cells. During the past decade, early detection strategies, such as serial measurement of EBV-DNA load in peripheral blood samples, have helped to identify high-risk patients and to diagnose early lymphoproliferation. Treatment options include manipulation of the balance between outgrowing EBV-infected B cells and the EBV cytotoxic T lymphocyte response and targeting the B cells with monoclonal antibodies or chemotherapy. Major challenges remain for defining indications for preemptive therapies and integrating novel and conventional therapies.

Figure 1

EBV latent life cycle. Virus enters though mucosal routes (shown is the buccal cavity), then infects normal naive B cells circulating through mucosal sites. Virus expresses type 3 latency, which drives B-cell proliferation and expands the infected memory pool. B-cell differentiation into the memory compartments occurs in germinal centers driven by type 2 latency proteins. Infected memory B cells exiting the germinal center down-regulate viral proteins and are invisible to the immune response. EBNA1 is expressed during homeostatic proliferation to maintain the latent viral episome. Virus replication is induced at mucosal sites, and virus is released into the saliva. PTLD indicates posttransplantation lymphoproliferative disease; HD, Hodgkin disease; NPC, nasopharyngeal cancer, and BL, Burkitt lymphoma.

Figure 2

Monitoring and treatment algorithm. Professional illustration by Debra T. Dartez.