Post-transplant Lymphoproliferative Disorders (PTLD)

Author: Courtney Misher, MPH, BS R.T.(T)

Last Reviewed: January 06, 2023

Post-transplant lymphoproliferative disorders (PTLD) are types of lymphoma that can happen after having a transplant. It can happen after:

A solid organ transplant (kidney, lung, heart, liver, lung).
An allogeneic bone marrow or stem cell transplant (cells from a donor).

PTLD is rare but is one of the most common post-transplant cancers. PTLD results from a rapid increase in lymphoid (immune) cells that can happen after transplant.

What causes PTLD?

In most cases, PTLD is thought to be caused by the Epstein-Barr virus (EBV) infection of B-cells. EBV is a type of herpes virus that 90% or more adults have already been infected with. Most people do not know they have had EBV. It stays in your body but is kept in check by your immune system. It does not cause long-term health problems. However, when combined with taking immunosuppressive medications after a transplant to prevent organ/graft rejection, the immune system cannot stop the B-cells infected with EBV from growing out of control. The virus may be reactivated, or you may have a new EBV exposure.

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 lower the chance of rejection.

Types of PTLD

There are four main types of PTLD outlined by the World Health Organization. They include

Non-destructive PTLDs which can often be reversed by lowering the dose of immunosuppressive medications. These include:
- Plasmacytic hyperplastic PTLD.
- Infectious mononucleosis PTLD.
- Florid follicular hyperplasia PTLD.
Polymorphic PTLD.
Monomorphic PTLD, the most common type.
Classic Hodgkin-type lymphoma the least common type.

Patients are most at risk for developing PTLD in the first few months after a transplant when doses of immunosuppressive medications are at their highest. However, it can develop years after transplantation.

Symptoms of PTLD

Symptoms of PTLD include:

Painless, swollen lymph nodes.
Fever.
Night sweats.
Weight loss.
Fatigue.
General discomfort.

It is important to talk to your transplant team right away about any new symptoms. If PTLD is suspected, you will likely need a biopsy. You may also need other scans and blood tests to determine the sub-type of PTLD.

Treatment of PTLD

PTLD treatment can be challenging. The type of PTLD is important in deciding what treatment is best for you. The goal is to cure PTLD while preserving the function of the transplanted organ. The most common treatments are:

Lowering the amount of the immunosuppressive medications you are taking.
Rituxan (rituximab).
Chemotherapy (doxorubicin, cyclophosphamide, vincristine, prednisone) in combination with rituximab (called R-CHOP).
Surgery or radiation therapy.

Antiviral medications, like ganciclovir and acyclovir, may be used to prevent EBV-related PTLD, but are not effective to treat PTLD. Other new therapies, like immunotherapy and targeted therapy, are being studied in clinical trials.

Resources for More Information

NORD PTLD: https://rarediseases.org/rare-diseases/posttransplant-lymphoproliferative-disorders/

Leukemia and Lymphoma Society PTLD Factsheet http://www.lls.org/sites/default/files/National/USA/Pdf/Publications/FS33_PTLD_2018_FINAL.pdf

References

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.

Bishnoi, R., Bajwa, R., Franke, A. J., Skelton, W. P., Wang, Y., Patel, N. M., ... & Dang, N. H. (2017). Post-transplant lymphoproliferative disorder (PTLD): single institutional experience of 141 patients. Experimental hematology & oncology, 6(1), 26.

Naik, S., Kamble, R. T., Hari, P., Kim, S., Chen, M., Komanduri, K. V., ... & Riches, M. L. (2018). Outcomes of Allogeneic Hematopoietic Cell Transplants with EBV Positive or EBV Negative Post-Transplant Lymphoproliferative Disorder (PTLD). Biology of Blood and Marrow Transplantation, 24(3), S370.

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.

Whitson, J. W., Snyder, L. D., & Zaffiri, L. (2018). Post-Transplant Lymphoproliferative Disorder: A Retrospective 17-Year Analysis. In C23. LUNG TRANSPLANT AND ACUTE ILD(pp. A4539-A4539). American Thoracic Society.