Overview of EBV+ PTLD and Its Impact on Patients

Jennifer Amengual, MD: Hi and welcome. Today, we'll be discussing EBV-positive post-transplant Lymphoproliferative disorder or EBV-positive PTLD, a serious complication that can arise following organ or hematopoietic stem cell transplantation. My name is Jennifer Amengual. I'm an associate professor at Columbia University Irving Medical Center, and I'm joined by two colleagues and experts in the field. I'm excited to have a chat with them. Welcome. Would you guys both please introduce yourselves?

Samuel Yamshon, MD: Hi, I'm Sam Yamshon. I'm an assistant professor of medicine at Weill Cornell Medicine, also in New York City.

Joe Schroers-Martin, MD, PhD: Great. I'm Joe Schroers-Martin. I'm an assistant professor of oncology at Stanford University in California.

Dr Amengual: Dr Schroers-Martin, could you describe what Epstein-Barr virus-positive or EBV-positive PTLD is and why it's a significant concern for those patients with transplants?

Dr Schroers-Martin: Sure. Let's start by talking a little bit about the Epstein-Barr virus. So, this is a member of the herpes virus family. It's a DNA virus, and it's something that we're all pretty much ubiquitously exposed to by adulthood. Clinically, in terms of initial infection, it's associated with mononucleosis or the kissing disease, which people frequently get during their teen years, and by adulthood, just about everyone has detectable, has had detectable EBV exposure. However, EBV, which has a tropism and tends to infect B cells, although it can involve other cells as well, has been associated with a number of other diseases. It's been associated with multiple sclerosis, most recently in work from Bill Robinson's lab and others. While in most adults, it tends to go into a latent phase where it is present just at very low and often undetectable levels, under circumstances of immunosuppression and particularly loss of T-cell immune control that can reactivate, it can come to the forefront. This can happen in older individuals without medical immunocompromised, just as part of immunosenescence, but most notably in patients undergoing solid organ or hematopoietic stem cell transplantation. Under the medical immunosuppression required to preserve the transplanted graft—the organ—EBV can reactivate either by itself, in the same way that other viruses like CMV can, but it can also reactivate and be a driver of lymphoma. That's a lot of what we're going to talk about.

Dr Amengual: I think it's different from hematopoietic stem cell transplant patients where often it comes from donor-derived B cells, whereas in organ transplant patients, it's often recipient-derived. We see that it has sort of two main sorts of patterns. It can happen early, so within the first few months after transplant, or late, where the late subtype is more commonly EBV—or not more commonly—but could be EBV-negative associated, whereas very early is almost uniformly EBV positive. As we see more and more indications for organ transplantation and stem cell transplantation and patients are surviving longer with organ transplants, we are seeing a really increased incidence of PTLD. It can really range in terms of organ transplants based on the type of transplant and the immunosuppression. We see that it's highest in patients with small bowel transplants and who are on high immunosuppression, followed by lung, then heart, liver, and kidney. So, I'm wondering just to hear how everyone's experiences have been with the burden of PTLD in patients who've had transplants.

Dr Yamshon: Our center is both a hematopoietic stem cell transplant center and a solid organ transplant center. I think we probably don't do quite as many lung, sorry, heart transplants as your center does. I know that your center is one of the biggest heart transplant centers in the country, but we have a decent number of liver and kidney transplants at our center. We do see some PTLD that occurs in those patients. I would say that the majority of the PTLD that we see in my practice is following a hematopoietic stem cell transplant. Part of that is due to volume, and part of that is also due to the fact that those patients are sort of predisposed due to both the amount of immunosuppression that they need as well as the length of immunosuppression, as well as in getting a transplant, you've wiped out the entire immune system. So, the amount of immunosuppression, I guess the deepest point of immunosuppression, is much deeper than in a solid organ transplant. So, we do see more aggressive and more frequent PTLDs in those populations, which can sometimes be more difficult to treat.

Dr Amengual: We do see a large number of organ transplant patients at Columbia, as it's an organ transplant center. So, we're sort of enriched for PTLD, and I can say it's very burdensome for the patient. These patients have undergone dealing with their organs that had been failing for a number of years, going through the whole process of undergoing an organ transplant and then being potentially diagnosed with lymphoma. Following all of that leads really a very heavy burden of disease on these patients. So, it is really important to find ways to predict PTLD, see if we can somehow prevent PTLD, and find better strategies for treating this disease that are less toxic and perhaps more specific to targeting this than just blanket chemotherapy that we use for other types of lymphoma.

Okay. Well, I really thank both of you for a great discussion on EBV-positive PTLD. I look forward to collaborating with you both in the future.  I think we still have so much to learn, and I think some of these new treatments that have emerged are going to pave the way for exciting times in this space.