Post-transplant Lymphoproliferative Disorders (PTLD): The Basics
What is PTLD?
Post-transplant lymphoproliferative disorders (PTLD) are a type of lymphoma that are a complication of both solid organ transplant (for example kidney, lung, heart, liver, lung) and allogeneic bone marrow or stem cell transplants (cells from a donor). PTLD is one of the most common post-transplant malignancies (cancers). PTLD results from a rapid increase in lymphoid (immune) cells that can develop after transplant.
What causes PTLD?
In most cases, PTLD is thought to be caused by Epstein-Barr virus (EBV) infection of B cells. EBV is a type of herpes virus that as much as 95% of the adult population is already infected with. Our immune system usually keeps the virus in check and EBV typically causes no long-term health problems. However, after transplant, the virus may be reactivated or the patient may experience a new EBV exposure. When coupled with taking immunosuppressive medications after transplant to prevent organ/graft rejection, the immune system cannot stop the B cells infected with EBV from growing out of control.
PTLD after bone marrow or stem cell transplant appears to be influenced by T cell depletion, which is often part of the transplant to help reduce the chance of rejection. With T cell depletion, the incidence of PTLD after BMT is around 1 in 200 patients. In patients who receive a solid organ transplant, the incidence of PTLD varies amongst what type of organ is transplanted. There is a higher risk among those receiving heart, lung, intestinal and multi-organ transplants (as high as 25%). In patients who have received a liver or kidney transplant, the incidence is lower; around 1-5%. Children who receive transplants may also be at a higher risk for developing PTLD. This is directly related to the fact that the child is unlikely to have been previously exposed to EBV, and therefore not have immunity to EBV that is present in the transplanted organ.
Types of PTLD
There are four main types of PTLD as classified in 2008 by the World Health Organization. The type of PTLD is important in identifying treatment strategies.
- Early hyperplastic lesions – can often be reversed by reducing immunosuppressive medications.
- Polymorphic lesions (polyclonal or monoclonal)
- Monomorphic lesions – most common type, often a diffuse large B cell lymphoma
- Classic Hodgkin-type lymphoma – least common
Patients are most at risk for developing PTLD in the first few months after transplant, when doses of immunosuppressive medications are at their highest. However, it can develop years after transplantation.
Symptoms of PTLD
Symptoms of PTLD can range from painless, swollen lymph nodes, to fever, night sweats, weight loss, fatigue and general malaise. It is important to communicate any symptoms to your transplant team as early as possible. If PTLD is suspected, you will likely need a biopsy to confirm the diagnosis, as well as other scans and laboratory tests to determine the sub-type of PTLD.
Treatment of PTLD
PTLD treatment can be challenging. The goal is to cure PTLD, while preserving the function of the transplanted organ. The first line of treatment is a reduction of the immunosuppressive medications the patient is taking. Additional therapies include the use of Rituxan (rituximuab) and other chemotherapy (doxorubicin, cyclophosphamide, vincristine, prednisone) in combination with rituximab (called R-CHOP).
Occasionally, surgery and radiation may be used to treat PTLD. Antiviral medications, including ganciclovir and acyclovir may be used to prevent EBV related PTLD, but have not demonstrated much success in the treatment of PTLD. Other new therapies, including immunotherapy and targeted therapy are being studied in clinical trials.
Resources for More Information
Lymphoma Association PTLD: https://www.lymphomas.org.uk/about-lymphoma/types/post-transplant-lymphoproliferative-disorder-ptld
AlDabbagh, M. A., Gitman, M. R., Kumar, D., Humar, A., Rotstein, C., & Husain, S. (2016). The Role of Antiviral Prophylaxis for the Prevention of Epstein–Barr Virus–Associated Posttransplant Lymphoproliferative Disease in Solid Organ Transplant Recipients: A Systematic Review. American Journal of Transplantation, doi 10.1111/ajt.14020.
Al-Mansour, Z., Nelson, B. P., & Evens, A. M. (2013). Post-transplant lymphoproliferative disease (PTLD): risk factors, diagnosis, and current treatment strategies. Current Hematologic Malignancy Reports, 8(3), 173-183.
San‐Juan, R., Comoli, P., Caillard, S., Moulin, B., Hirsch, H. H., & Meylan, P. (2014). Epstein‐Barr virus‐related post‐transplant lymphoproliferative disorder in solid organ transplant recipients. Clinical Microbiology and Infection, 20(s7), 109-118.
Singavi, A. K., Harrington, A. M., & Fenske, T. S. (2015). Post-transplant lymphoproliferative disorders. In Non-Hodgkin Lymphoma (pp. 305-327). Springer International Publishing.
Taylor, A. L., Marcus, R., & Bradley, J. A. (2005). Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Critical Reviews in Oncology/Hematology, 56(1), 155-167.
Trappe, R., Oertel, S., Leblond, V., Mollee, P., Sender, M., Reinke, P., ... & Morschhauser, F. (2012). Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. The Lancet Oncology, 13(2), 196-206.