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Publications
Response to Rituximab Induction Is a Predictive Marker in B-Cell Post-transplant Lymphoproliferative Disorder
Journal of Clinical Oncology
2017;35(5):563-543
Post‐transplant Lymphoproliferative Disorders, Epstein‐Barr Virus Infection, and Disease in Solid Organ Transplantation
Clinical Transplantation
2019;33(9):e13652
Clinical Outcomes of Solid Organ Transplant Patients with EBV+ PTLD Who Fail First-Line Rituximab or Rituximab Plus Chemotherapy
Poster and abstract presented at: 24th Congress of European Hematology Association Meeting
June 13-16, 2019; Amsterdam, Netherlands
Real-World Outcomes With Rituximab-based Therapy for Posttransplant Lymphoproliferative Disease Arising After Solid Organ Transplant
Transplantation
2020;104(12):2582–2590
Failure of Rituximab Is Associated With a Poor Outcome in Diffuse Large B Cell Lymphoma-type Post-transplant Lymphoproliferative Disorder
British Journal of Haematology
2020;189(1):97-105
Management of Epstein-Barr Virus Infections and Post-transplant Lymphoproliferative Disorders
Haematologica
2016;101(7):803-811
EBV-associated Post-transplant Lymphoproliferative Disorder Following In Vivo T-cell-depleted Allogeneic Transplantation
Bone Marrow Transplantation
2014;49(2):280-286
Clinical Outcomes of EBV+ PTLD Patients Following HCT Who Fail Rituximab
Abstract
Current Understanding of the Role of Epstein-Barr Virus (EBV) in Lymphomagenesis
Leukemia & Lymphoma
2008;49(suppl 1):27-34
Upcoming Congresses
Learn more about EBV+ PTLD at select upcoming congresses:
Video Library
Risk Factors in Kidney Transplant Recipients
Dr Adnan Sharif
Consultant Transplant Nephrologist, Birmingham, UK
We consider all of our kidney transplant recipients are high risk for cancers and we counsel them appropriately. But we know that there’s certain people are a slightly higher risk of developing PTLD and especially people with their net burden of immune suppression is going to be a lot higher. So, depending on what induction therapy people get for transplantation, if people are immunologically high risk, so we’re going to be giving them a high burden of immune suppression. Or people who may have rejection or steroid-resistant rejection, so we’re increasing their level of immune suppression. Separate to that, there’s people who have an EBV mismatch so they are EBV naive and they’re receiving a kidney from someone who is EBV positive. We tend to see that more commonly in our younger kidney transplant recipients.
Risk Factors in Lung Transplant Participants
Dr Jasvir Parmar
Consultant Transplant Respiratory Physician, Cambridge, UK
Lung transplant recipients are at significantly higher risk of developing PTLD for two main reasons. The first of these being that they receive a much higher volume of lymphoid tissue in their graft and in relationship to that they can experience much higher instance of PTLD. The second reason is that the requirement for immunosuppression is significantly higher in lung transplant recipients, which means that their defense mechanisms are significantly lower than other solid organ recipients.
In the UK, most lung transplant patients are followed up lifelong in the center and so we see them for good. And it’s very occasional that other patients may choose not to come, but by and large we follow all of our patients for life. In the small number that are followed up remotely, we provide a sort of standard of care operating protocol for the physicians involved with a detailed sort of algorithm for them to follow. And, generally speaking, if there are any complications such as a lymphoma or infections, then the patient will still return to the center for their care.
Identifying EBV+ PTLD Risk Factors in Heart Transplant Recipients
Dr Sern Lim
Consultant Cardiologist, Birmingham, UK
I think there are unique features in heart transplantation and one of the biggest challenges is really the availability of the organs. There are far fewer heart transplants done compared to a lot of the other solid organs. And that’s largely because of the—the availability of organs.
And this is a very precious resource. It’s our obligation to try and maximize the longevity of these donor organs. And that—that’s a real challenge in heart transplantation. And conditions such as EBV PTLD has an impact on this, on the survival of these patients, so from my point of view, heart transplantation is unique in the sense that—that there’s no replacement, unlike kidney transplant, for example. Or even pancreatic transplant where you have enzyme replacement, there is no replacement therapy for heart transplantation if the organ fails. And, we want to maximize this limited resource as much as possible.
The way we would try and identify patients following heart transplantation who may be at high risk of developing EBV PTLD would be based on largely symptoms and blood tests. We would look for obviously EBV, measurements, in the blood. We would have some idea prior to transplantation what the EBV status is, although vast majority of transplant recipients will be EBV positive. We will follow them up with serial blood tests and if they have symptoms, we would then look a bit harder into possible PTLD.
Recipients
RIS in Heart Transplant
Recipients
Dr Sern Lim
Consultant Cardiologist, Birmingham, UK
Reduction in immunosuppressant therapy is one of the management strategies that we use in the face of PTLD. In a heart transplantation there is a risk of rejection, and rejection in heart transplantation could be life threatening, and that’s obviously quite a serious complication of a reduction in immunosuppression therapy. We would perform regular surveillance including biopsies and echocardiograms to monitor graft function with reduction in immunosuppression therapy, and we would probably reduce that in a stepwise fashion because of the risk that the patients will be exposed to. We have had instances of rejection, when we reduce immunosuppression therapy, needing, escalation of immunosuppression therapy to overcome the rejection. Um, and certainly this will expose patients to potentially life-threatening complications. So, it is a serious step to take for treatment of PTLD.
And that’s also one of the reasons why we hesitate initially to try and reduce immunosuppression therapy significantly so we would do it in a more stepwise fashion.
EBV+ PTLD Pathogenesis
Dr Christopher Fox
Consultant Hematologist, Nottingham University Hospitals NHS Trust, Nottingham, UK
EBV is a naturally oncogenic virus and although 95 percent of the adult population in the world is infected with EBV, importantly it needs very good T-cell responses both in terms of T-cell numbers and function to maintain control of the virus over our lifetime. So perhaps it’s no surprise then, if we reduce the numbers of effective T cells or the function of T cells, that there’s a risk that EBV can drive a lymphoproliferative process through expression of a range of latent proteins.
PTLD that occurs following a stem cell transplant is directly related to the depth and duration of T-cell immunosuppression and these lymphoproliferative disorders that we term PTLD can be very aggressive clinically.
of EBV+ PTLD Patients
Monitoring and Evaluation
of EBV+ PTLD Patients
Dr Christopher Fox
Consultant Hematologist, Nottingham University Hospitals NHS Trust, Nottingham, UK
In terms of monitoring EBV viral load following stem cell transplant, most centers now will adopt a weekly monitoring schedule usually coinciding with the patient’s visit to the clinic and that we would continue monitoring weekly and typically for at least four-to-six months.
We described a relatively large cohort of cases that we published in BMT a few years ago of patients with proven or probable PTLD. One important finding in that setting was the wide variability between patients of the level of EBV DNAaemia at the time of PTLD diagnosis. That varied over a number of log10 scale so it’s quite a significant variability. I think the important message from that finding is that one shouldn’t discount the possibility of PTLD with a patient with a relatively low or modest viral load.
For patients at risk of or developing PTLD after stem cell transplant, key points for clinicians to remember would include having a low index of suspicion. So any patient who has symptoms that aren’t easily explained, such as a fever that’s not explained by other etiologies, or B symptoms, or unexpected lymphadenopathy, then we really need to have PTLD at the top of the differential diagnosis. It can present quite heterogeneously, so in those patients we need to be doing an urgent EBV viral load and often, proceeding to cross-sectional imaging with either CT or PET-CT.
in HCT Patients
Filmed in December 2018.
EBV+ PTLD Pathogenesis
in HCT Patients
Filmed in December 2018.
Dr Mohamad Mohty
Professor of Hematology, University Pierre & Marie Curie, Paris, France
Allogeneic stem cell transplantation is the only curative therapy currently available for many hematologic malignant and non-malignant disease. Unfortunately, these patients are highly immunosuppressed in general, and they can also develop complications like a graft-versus-host disease where they would need, even, a long-term immunosuppressive therapy and high-dose steroids. When it comes to immunosuppression, unfortunately, this is where we see in these patients viral reactivations. One significant and major complication we see is the EBV reactivation and the development of EBV-related lymphoma and this is usually about the proliferation of these B cells, usually from the donor, which integrated the virus EBV.
in HCT Patients
Filmed in December 2018.
EBV+ PTLD Risk Factors
in HCT Patients
Filmed in December 2018.
Dr Mohamad Mohty
Professor of Hematology, University Pierre & Marie Curie, Paris, France
One needs to be reminded that there are some specific risk factors that may aggravate or increase the incidence of viral reactivations like CMV or EBV or even the development of EBV PTLD. For example, a T-cell depletion whether in vitro or in vivo, the use of numerous immunosuppressive therapies, the use of high-dose steroids for a long-term period, the use of mismatched donors—all of these situations can lead to an increased risk of EBV reactivations and, at some point, development of EBV PTLD.
of HCT Patients
Filmed in December 2018.
Importance of Close Monitoring
of HCT Patients
Filmed in December 2018.
Dr Mohamad Mohty
Professor of Hematology, University Pierre & Marie Curie, Paris, France
When it comes to serious and severe complications after allogeneic stem cell transplantation, improving outcomes goes together with very close monitoring of the patient. One needs to pay attention to the clinical symptoms of course but, actually, in those patients who, for example, are at higher risk of viral complications, viral reactivation you need to establish a very close and very precise monitoring of the viral load and whenever there is a suspicion about a tumoral mass, then you need to use the imaging techniques—CT scan, PET scan—because we know very well that a rapid and very quick intervention is crucial towards improving the outcome of these patients.
and Diagnosis of PTLD
Heterogeneous Presentation
and Diagnosis of PTLD
Dr Ralf Ulrich Trappe
Professor of Medicine, Bremen, Germany
Patients with EBV viremia are at a high risk for EBV-associated PTLD. Patients with PTLD may be symptomatic presenting with B symptoms like night sweats or unexplained fever. On the other hand, some patients just present with a lymphatic mass or some kind of lymphadenopathy showing up during the regular follow-up with it in the transplant center, and diagnosis finally is made in these patients by histology, so the pathologist is the one making the diagnosis of PTLD.
in PTLD
Reducing Immunosuppression
in PTLD
Dr Ralf Ulrich Trappe
Professor of Medicine, Bremen, Germany
The most important information from the transplant team is the kind and demand of the immunosuppression of the patient. As a result of the immunosuppression, patients after solid organ transplantation are at a higher risk for infectious toxicity.
On the one hand, you can reduce the amount of immunosuppression which always increases the risk of graft rejection, and therefore another information that is required is the number of rejection episodes in the patient that is presenting with a PTLD.
Therefore, the amount of immunosuppression, as well as the substances given to the patients, are very important for making a treatment decision in PTLD.
Impact of PTLD on Patients
Dr Ran Reshef
Associate Professor of Medicine, Columbia University Irving Medical Center, New York, NY
There are several ways of optimizing outcomes for PTLD, and I’m sure for many of my colleagues this is a very important complication of transplant. We think about it as a man-made disease that does not exist when we don’t transplant patients, so we created it, so we should fix it. And it has a significant impact on patients’ quality of life, and a significant psychological impact. These are mostly patients who have had a significant medical event, either a hematopoietic stem cell transplant, or a liver transplant, or lung transplants to cure one disease. Sometimes within even a few months they’re diagnosed with PTLD, which can be a life-threatening lymphoma.
EBV+ PTLD: A “Man-Made” Complication of Transplant
Dr Ran Reshef
Associate Professor of Medicine, Columbia University Irving Medical Center, New York, NY
I’m sure for many of my colleagues this is a very important complication of transplant. We think about it as a man-made disease that does not exist when we don’t transplant patients, so we created it, so we should fix it. And it has a significant impact on patients’ quality of life, and a significant psychological impact. These are mostly patients who have had a significant medical event, either a hematopoietic stem cell transplant, or a liver transplant, or lung transplants to cure one disease. And sometimes within even a few months they’re diagnosed with PTLD, which can be a life-threatening lymphoma.
So, there is first of all importance in being aware, so increasing the awareness to this complication is very important, because that would lead you to monitor patients more frequently and more aggressively. And of course, also when patients present already with symptoms, PTLD should be on the top of our minds when thinking about the potential diagnosis that could occur in a patient who had an organ transplant or a hematopoietic stem cell transplant.
Awareness of PTLD
Importance of Increasing
Awareness of PTLD
Dr Ran Reshef
Associate Professor of Medicine, Columbia University Irving Medical Center, New York, NY
So, there is first of all importance in being aware, so increasing the awareness to this complication is very important, because that would lead you to monitor patients more frequently and more aggressively. And of course, also when patients present already with symptoms, PTLD should be on the top of our minds when thinking about the potential diagnosis that could occur in a patient who had an organ transplant or a hematopoietic stem cell transplant.
