Epstein-Barr Virus-Related Post-Transplantation Lymphoproliferative Disorders After Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Epstein-Barr virus (EBV)-related post-transplantation lymphoproliferative disorders (EBV-PTLDs) are rare but potentially fatal complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by uncontrolled proliferation of EBV-infected lymphocytes. The most common risk factors include T cell depletion of graft, HLA mismatch, severe graft-versus-host disease (GVHD), and EBV seromismatch (recipient-negative/donor-positive), among others. EBV-PTLDs commonly manifest as fever and lymphadenopathy and may rapidly progress to multiorgan failure and even death. Histopathological evidence is indispensable for the diagnosis, and positive findings of EBV-DNA (EBV-DNAemia) and imaging are also very helpful. Active prophylaxis, such as optimization of the donor choice, conditioning regimen, and GVHD prevention, or passive prophylaxis, such as low dose of rituximab, unselected donor lymphocyte infusion (DLI), and EBV-specific cytotoxic T lymphocyte (EBV-CTLs) infusion, can decrease the incidence of EBV-DNAemia. Rituximab- based preemptive treatment can prevent EBV-DNAemia from developing into EBV-PTLDs, particularly benefiting recipients with higher loads of EBV-DNA, although the long-term outcome has not been significantly improved. To date, there is no consensus as to whether and when to initiate prophylactic or preemptive treatment. The current treatment strategies for probable and proven EBV-PTLDs include reduction of immunosuppression (RI), rituximab, adoptive cell therapy (DLI or EBV-CTLs), chemotherapy, radiotherapy, and surgery, among which rituximab plus RI is the mainstay. However, the mortality of EBV-PTLDs remains considerably high, and novel strategies merit exploration.

Torque Teno Virus Viral Load as a Marker of Immune Function in Allogeneic Haematopoietic Stem Cell Transplantation Recipients

“…In the present study, we observed that at 6 months post-transplant during the immune reconstitution period, some patients are still unable to regulate the TTV replication, leading to high blood viral load, despite a sufficient number of T-cells. This observation has also been reported for other viruses such as cytomegalovirus (CMV) or Epstein–Barr virus (EBV) [ 9 , 27 , 28 ]…”

Anti-Thymocyte Globulin Prophylaxis in Patients With Hematological Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: An Updated Meta-Analysis

“…The systemic immunosuppressive conditioning regimens plus ATG might delay immune reconstitution and thus increase the risk of infectious complications. Thus, EBV was associated with the post-transplantation lymphoproliferative disorder ( 28 , 29 ). Our pooled analysis showed that ATG increased subsequent EBV reactivation, while the incidence of general infection complications, CMV reactivation, and fungal infection did not change significantly.…”

An outlook on antigen-specific adoptive immunotherapy for viral infections with a focus on COVID-19

“…The use of VST cells for viral infections has a promising history, especially for the prevention or treatment of post-transplant opportunistic infections in the immunocompromised allogeneic bone marrow (allo-BM) recipients [2] , [51] , [52] , [53] , [54] , [55] , [56] . Many trials have shown that CMV-, EBV- and/or…”

“…AdV-specific T cells were adequately immunoprophylactic to render the allo-BM transplanted patients viral-free for long-term. These VSTs were generated via 3 general strategies [2] , [51] , [53] , [54] , [55] , [56] , [57] : (1) coculture of seronegative donor-derived naïve T cells with the virus-specific Ag-loaded APCs ( Fig 3 c ), (2) activation and immunoadsorption of seropositive donor-derived PBMCs using viral protein-derived multimers or peptide pools and subsequent isolation of VST cells from the PBMCs using multimeter-based or IFN-γ capture-based immunomagnetic cell sorting ( Fig 3 d ), (3) genetic engineering of autologous T cells using gene vectors encoding the TCR specific to essential surface antigens of the virus ( Fig 3 e ). Additionally, there have been some efforts to engineer the CAR-bearing T cells for CMV and EBV that are effectual in an MHC-independent manner ( Fig 3 f ), though such CAR T cells merit further research and fine tunes in order to enter the clinical protocols [2] , [50] .…”