About EBV

Epstein-Barr virus (“EBV”), a member of the herpesvirus family, is extremely common worldwide. In the U.S., about half of all children aged five and about 90% of adults have serological evidence of infection. Childhood cases rarely produce meaningful symptoms, however, in adolescents and young adults, EBV infection may cause infectious mononucleosis (“IM” or “mono”). EBV is primarily transferred through saliva, but can also be spread through other bodily fluids including blood and semen.

Once an individual is infected with EBV, the virus lies dormant in infected cells and can remain that way for years before reactivating. EBV infection or reactivation can lead to serious complications in hosts whose immune systems are either compromised by disease or suppressed, which is common following stem cell and solid organ transplants.

Transplant Procedures

Hematopoietic stem cell transplants (“HSCT”) have demonstrated success in treating a range of conditions, including many cancerous and non-cancerous diseases of the blood. This procedure involves isolating stem cells from a donor and transferring them to a recipient. These stem cells can then differentiate into the types of blood cells needed for the recipient’s body and immune system to function normally. The stem cells can be derived from multiple donor sources, including bone marrow, peripheral blood, or umbilical blood.

Patients undergoing HSCT or solid organ transplant procedures are at-risk of EBV reactivation or active infection due to immunosuppression. Immunosuppression can be dangerous as it may allow for opportunistic pathogens which normally would not cause any issues, like latent EBV, to emerge and cause disease. There is a fine balance in transplant cases between ensuring that the body accepts the transplant and that the immune system is strong enough to fend off other potential diseases.

A surgeon performs a bone marrow harvest operation.

Post-transplant Lymphoproliferative Disorder

A common and potentially life-threatening EBV-associated complication in immunocompromised transplant patients is post-transplant lymphoproliferative disorder (“PTLD”). PTLD is a disorder where the host’s immune cells proliferate uncontrollably following transplant immunosuppression.

PTLD has a spectrum of presentations, ranging from the benign growth of B cells to Non-Hodgkin’s lymphoma, a group of blood cancers characterized by excessive growth of lymphocytes. Approximately 70% of PTLD cases involve EBV; the pathogenesis in the other 30% remains unclear, but may be due to other viral infections.

EBV-seronegative patients may be exposed to EBV if the transplant donor is seropositive. EBV-seronegative patients with a primary EBV infection are much more likely to develop PTLD. Pediatric transplant patients are at an increased risk, as only half have been infected by the EBV virus by age five, and are therefore more likely to develop PTLD.

Ideally, a seronegative patient would be matched with a seronegative donor to avoid complications like PTLD. However, finding suitable donors is a challenge because 90% of the adult population has been infected with EBV.

Standard of Care

Unlike many other viruses, EBV reactivation cannot be prevented with antiviral therapies. Similarly, there is currently no prophylactic vaccine for EBV. Treatment strategies depend on the EBV serostatus of the patient and PTLD presentation. The therapeutic goal is to either prevent or cure the disease while preserving the transplant.

The first line of treatment for PTLD is to reduce the dosage of the immunosuppressant drugs. If this does not work, rituximab, a monoclonal anti-CD20 antibody, is recommended. The combination of these two treatments is associated with a positive outcome in approximately 70% of patients. Second-line therapies include chemotherapy and unselected donor lymphocyte infusions.

Opportunity

EBV is a common cause of complications following HSCT and solid organ transplants. These complications range from mild to fatal. Additionally, a transplant from a EBV-positive donor to a EBV-negative recipient is associated with an increased risk of EBV-related disease. Therefore, a treatment to deactivate EBV in infected cells before transplant procedures could significantly reduce both EBV-related disease and the side effects of EBV treatment in transplant recipients.

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