Wiping Out Epstein-Barr Virus Preserves Transplant Success

Pictured: Susan Prockop & Lucas T.

Lucas T., a patient, with Susan Prockop, who leads research into Epstein-Barr virus.

Memorial Sloan Kettering physician-scientists are investigating a novel way to wipe out a potentially devastating complication that commonly occurs in patients who have received a stem cell or organ transplant as part of their treatment. These transplants can weaken the immune system, allowing a dormant pathogen called Epstein-Barr virus (EBV) to awaken and trigger a new malignancy.

Epstein-Barr virus (EBV) is present in most people, but in those with a healthy immune system it may produce only mild symptoms or even go unnoticed. However, in someone whose immune system is not fully functional, EBV can cause infected cells to divide uncontrollably as a cancer in the lymph nodes, spleen, or even the liver, lungs, or brain. This can occur in both children and adults.

“This kind of transplantation complication is life threatening,” says Memorial Sloan Kettering pediatric oncologist Susan Prockop. “Historically, the life expectancy for somebody who developed an EBV lymphoma, the most common of these malignancies, was less than 30 days.”

A Third-Party Remedy

The new approach involves giving these patients T cells (a type of immune cell) from a healthy third-party donor — someone not related to either the patient or any donor who previously gave blood or tissue to the patient. Once infused, the third-party T cells attack all EBV-infected cells, cancerous or not, and destroy them.

The third-party donors need to have been exposed at some point to EBV so their T cells recognize the virus. They also are matched with the recipient based on human leukocyte antigen (HLA) type. HLAs are proteins that vary between people and function as the “fingerprint” of an individual’s immune system. The HLA match need not be perfect but should be close enough that the donated T cells attack EBV effectively in the recipient’s cells.

The T cells from the third-party donor’s blood are cultured in the laboratory in a way that expands them to sufficient numbers to be therapeutic after infusion, a process that takes about two months.

Using a third-party donor — rather than the person who donated stem cells for the original transplant — can offer several advantages, Dr. Prockop explains. “Some stem cell or organ donors have never had EBV, so their T cells wouldn’t recognize the virus in the recipient effectively,” she says. “Also, the patient may develop the EBV malignancy before cells from these donors have been collected and expanded in the laboratory, and the patient can’t wait two months for this to occur. Finally, EBV malignancies can develop in non-transplant patients — their immune systems may be weakened from other causes.”

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“Off-the-Shelf” Therapy

The researchers have now characterized more than 300 cell lines that are frozen and stored, meaning they are available as a kind of “off-the-shelf” resource when needed. This is essential in treating EBV malignancies, which tend to progress very rapidly.

Dr. Prockop says the third-party T cells have so far shown no undesirable side effects and the researchers are conducting a phase II clinical trial establishing the treatment’s long-term safety and effectiveness. The new approach has been used on 53 patients, both children and adults, and results have been promising. “We’re now being referred patients from all over the country to treat these EBV malignancies,” she says.

On March 1, Dr. Prockop presented results at the 2014 BMT Tandem Meeting in the Dallas area focused specifically on the treatment of EBV lymphoma using third-party T cells. Of 35 patients treated for this aggressive malignancy, 17 had complete remission, six had partial remission, and two had stable disease — meaning the lymphoma did not progress.

“These patients have absolutely no other recourse, so it is very striking to have such an effective therapy with no side effects,” she says.

Dr. Prockop adds that caring for patients allows her to see the clinical problem first-hand and drives home the urgency of finding a solution for patients who have already been through an ordeal and now have a terrible complication. “It’s the best version of oncology — the excitement of seeing our efforts make these children better while studying these EBV-directed T cells, trying to figure out how they work, why they work, and how we can make it better to help patients with no other options.”

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Commenting is disabled for this blog post.

It's a wonderful goal to try and wipe out Epstein-Barr.

Great hospital. Dr. Prockop along with her team provided the utmost care and concern for our son. Was always available to answer our questions and concerns regarding all treatment procedures. Keep up the great work!!

I've heard about a new ultraviolet machine called the UVLRx that's being used for Epstein Barr patients. It uses a fiber optic thread which is inserted directly into the vein and the treatment lasts for an hour, so all the blood is treated. Has anyone tried this?

Thank you for your comment. We consulted with Memorial Sloan Kettering pediatric oncologist Susan Prockop, who responds:

We have not used this therapy.

There is no evidence that treating the infected cells with UV light treats the EBV infection. UV therapy will kill normal lymphocytes but not necessarily EBV infected lymphocytes and only kills what is in the blood. Since lymphocytes traffic to and live in lymph nodes this therapy can’t get to those cells.

My doctor ran a test to see if I had Epstein-Barr virus reactivation and I do. They ran cancer tests on me because all of my lymph nodes on my body were swollen and I lost 50 pounds. All the tests came up negative but the virus and it's symptoms still persists. I have had many more horrible symptoms from this which I won't get into now. Would I be a candidate for this type of therapy to kill off the EBV virus even though my cancer test came back negative? If not is there any type of help out there for people suffering with this horrible virus?

Alex, unfortunately this therapy is being studied only in people who actually have lymphoma or cancer. The reason for that is that the T cells can only target and kill cells that are expressing EBV in the way that cancer cells do.

At this time we are not aware of any T cell therapy available for people where EBV is causing other problems, but we are working to develop T cell therapy that will be better at seeing EBV even when it is more dormant or latent in cells. We recommend you continue checking to see if a trial opens for which you would be eligible.

Any updates or new publications on this treatment? My son has just suffered a relapse of EBV+ NK T Cell Lymphoma where EBV seems to be a integral part of his cancer. Hopes are in conjunction with Children’s Hospital in Knoxville, TN and Cincinnati Children’s we may be able to connect with your wonderful research.

Brad, thank you for reaching out. At MSK, our doctors are looking at combination therapy with transplant in selected patients with NK T lymphoma. If your son is a pediatric-age patient, you could contact Dr. Susan Prockop at 212-639-6715 to see about a consultation.

If he is over the age of 25, we suggest you contact Dr. Parastoo Dahi at 877-836-ABMT (2268) to see about an appointment to discuss options.

I am on a kidney transplant list and actively seeking a living donor, but just found out I had undiagnosed EBV last spring. Is it crazy to keep pursuing the transplant? Of, course I will have to receive immune suppression afterwards. My team said it is good that I've had EBV because I have antibodies, but that is not what I'm reading.

Dear Judy, MSK is a cancer hospital and doesn’t do organ transplants. We recommend that you discuss this with your doctor or with a specialist who does organ transplants. Thank you for your comment, and best wishes to you.

Hi, I have heard about the benefits of UV light treatment for EBV. I do not have lymphoma, but have had several EBV recurrences in recent years. Are you able to recommend a place in NYC that provides this treatment? I am in desperate need of relief from this terrible virus! Thank you!

Dear Katherine, we recommend that you discuss this with your doctor. Thank you for your comment, and best wishes to you.

This is all great news. Keep up the great work. Like some of the others, I have EBV and suffer from flare ups. Living in a rural state, I am curious if you have any recommendations for places to be treated for EBV flare up/reoccurrences. This is a much bigger problem than realized, I hope to find a place to help me recover.

Dear Chris, we recommend that you ask your doctor for a referral to a specialist in your area, Often, this will be someone at an academic medical center. Thank you for your comment and best wishes to you.