Post-transplant Lymphoproliferative Disorders

Introduction:

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening condition that includes a wide range of lymphoproliferative disorders such as reactive polyclonal hyperplasia, aggressive non-Hodgkin's lymphoma, etc. Studies have shown that the majority of post-transplant lymphoproliferative disorders (approximately 90 percent of PTLD) come positive for Epstein-Barr virus (EBV), which is referred to as (EBV-PTLD).

What Are Post-transplant Lymphoproliferative Disorders?

Post-transplant lymphoproliferative disorders are the uncommon side effects of hematopoietic stem cells and solid organ transplants. In addition, immunosuppressive treatment and the Epstein-Barr viruses are linked to post-transplant lymphoproliferative disorders. Therefore, drugs that inhibit the activity of the immune system (referred to as immunosuppressive medications) are administered to patients who undergo these transplants.

As the transplant is a foreign substance, there is always a risk that the body's immune system might identify it as an invader and will reject it. Therefore, to support the body in accepting the transplant and preventing rejection by the body's immune system, the physicians have to suppress the immune system. These medications are given to patients as part of their induction therapy (before or during transplantation), and they have to take them for the rest of their lives (maintenance therapy).

In addition, because of this suppression of the immune system, infections and, in some cases, post-transplant lymphoproliferative disease are more likely to develop in patients receiving immunosuppressive therapy. These disorders require prompt diagnosis and treatment as early as possible.

What Are the Causes of Post-transplant Lymphoproliferative Disorders?

The causes of post-transplant lymphoproliferative disorders are listed below:

1. Infection With the Epstein-Barr Virus (EBV): EBV attacks B-cells of the immune system. This virus has an active phase, and when this active phase gets over, the virus stays in the body in the latent phase (dormant or sleeping). EBV infection usually occurs first in childhood or sometimes in teenage or adulthood. After this infection, the virus goes into an inactive phase. However, the reactivation of EBV-infected B- cells of the immune system occurs in patients who are under immunosuppressive treatment and recently underwent a solid organ or hematopoietic stem cell transplant.

2. Infection From the Donor Organ: Occasionally, donor organs can bring post-transplant lymphoproliferative disorders. The reactivation and out-of-control growth of the EBV-infected B-cells from the donor organ can cause these disorders. Usually, this is commonly seen in people undergoing hematopoietic stem cell transplants.

In addition, during the donation of an organ or a stem cell, other cells, including B-cells, are also donated. However, if the donor had suffered EBV infection previously, the EBV-infected B-cells, which are in the dormant or sleeping phase, also get transferred to the recipient. Post-transplant lymphoproliferative disorders also occur when a patient undergoing transplant gets infected with EPV for the very first time.

However, studies have shown the occurrence of post-transplant lymphoproliferative disorders in patients who were not infected with EPV. The occurrence of these disorders in the absence of EBV infection is still not known.

What Are the Risk Factors of Post-Transplant Lymphoproliferative Disorders?

The risk factors of post-transplant lymphoproliferative disorders are listed below:

• Viral Infections (EPV): EBV viral infection poses a major risk of getting these disorders.

• Degree of Immunosuppression: The occurrence rate of these disorders is higher in heart, lung, intestinal, and multiple organ transplants because the degree of immunosuppression is higher in these transplants. In addition, the occurrence of these disorders is less in kidney and liver transplants because the degree of immunosuppression is less in these transplants.

• Age of Recipient: Studies have shown that patients aged less than ten years or more than 60 years are at a higher risk of getting these disorders. Patients under ten years of age are at high risk because of their frequent negative EBV status at the time of transplant. In addition to this, their tendency to develop primary EBV and CMV (cytomegalovirus) infections in the initial phase of the post-transplant course also increases the risk.

However, older individuals aged more than 60 years are likely to develop these disorders because of low immunity.

• Race of Recipient: White patients are at higher risk of developing these disorders as compared to black patients in the case of a kidney transplant, regardless of the EBV serostatus of the recipient.

• Type of Allograft: Stem cell donations from unrelated donors or those stem cells which are mismatched based on tissue type, increase the risk of getting post-transplant lymphoproliferative disorders.

• Genetic Variations of Host: Genetic factors can also predispose to the development of post-transplant lymphoproliferative disorders. These include genetic variations in cytokine genes (interleukin-10 and interleukin-6) and variations in several other genes.

What Are the Symptoms of Post Transplant Lymphoproliferative Disorders?

The symptoms of post-transplant lymphoproliferative disorders are listed below:

• Fever.

• Weight loss.

• Sweats.

• While some patients affected by these disorders experience a mild, noncancerous (benign) overgrowth of the affected tissue, others may develop a cancerous, fatal form of lymphoma.

• Symptoms occur based on the type of organ involved.

• Enlargement of lymph nodes can occur.

• Tiredness.

• Malaise.

What Are the Treatments of Post Transplant Lymphoproliferative Disorders?

The treatment plan for post-transplant lymphoproliferative disorders is as follows:

• Tapering the dose of immunosuppressive drugs.

• Surgery can be done to remove the tumor or the surrounding lymph nodes caused by these disorders.

• Use of Rituximab medicine for the treatment of EBV infection.

• Chemotherapy can be given in conjunction with Rituximab.

• Radiation therapy.

• Antiviral therapy.

• Adoptive immunotherapy.

How Are Post Transplant Lymphoproliferative Disorders Diagnosed?

The diagnosis of post-transplant lymphoproliferative disorders is made by the following:

• Studying the symptoms.

• Patient history.

• Clinical evaluation.

• Complete blood count (CBC).

• X-rays and other imaging techniques.

• Epstein-Barr virus infection evaluation.

• Tissue biopsy.

Conclusion:

Post-transplant lymphoproliferative disorders are the complications of transplant procedures. Whenever an organ stops functioning, it can be replaced by another healthy organ from a donor with the help of a transplant procedure. However, sometimes these transplants can bring infections and disorders like post-transplant lymphoproliferative disorders, which can be fatal and turn into cancer. EBV infection is the primary cause of these disorders. The treatment of these disorders involves the same treatment as cancer, including radiotherapy and chemotherapy.