1. Are transplant recipients at greater risk for the development of malignancies?

Yes. The chronic exposure to immunosuppressive agents increases the long-term risk of malignancy by two to threefold compared with the general population of the same age and sex. Kidney transplant recipients have the cancer risk of a nontransplanted individual 20 to 30 years older than them. If a recipient had a cancer prior to transplant, the risk post transplant is increased by 40%. See Fig. 59.1 .

Risk of developing malignancies in transplant recipients compared with the general population.

2. What are posttransplant lymphoproliferative diseases (PTLD) and the risk factors?

PTLD is a well-recognized complication of the immunosuppression in the kidney transplant patient. Epstein-Barr virus (EBV) is found in two-thirds of PTLD cases. PTLD in kidney transplant patients is mainly a B cell–derived, large cell lymphoma.

Risk factors for PTLD include:

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  Degree of immunosuppression such as the use of lymphocyte-depleting agents

  
  
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  Transplantation between EBV-positive donor and EBV-negative recipient

  
  
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  <25-year-old recipient

  
  
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  Pretransplant malignancy

  
  
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  PTLD occurs in 0.6% to 1.5% of patients after kidney transplantation, with the majority in the first year

3. How common are lymphoproliferative disorders following transplantation?

Excluding nonmelanoma skin cancer and in situ cervical cancer, lymphoproliferative disorders are the most common malignancies complicating organ transplantation. Lymphoproliferative disorders account for 21% of all malignancies in patients who have received transplants, compared with 5% of malignancies in the general population. Lymphoproliferative disorders occur in 5% of patients who have received a kidney transplant.

4. Does PTLD have the same characteristics as lymphoproliferative disease in the general population?

No, the proportion of patients with non-Hodgkin lymphoma (NHL) is much higher in transplant patients (95%), whereas NHL accounts for only 65% of lymphomas in the general population.

5. What is the clinical presentation of PTLD?

PTLD can be divided into “early” and “late.” Early PTLD is seen in younger patients who have a de nova EBV infection. The kidney allograft is involved in 57% of cases. This is responsive to immunosuppression reduction. Late PTLD occurs after the first year and is usually more disseminated and does not respond as well to immunosuppression reduction. Most patients present with nonspecific complaints, including fatigue, weight loss, and fever. Some patients present with symptoms resembling infectious mononucleosis. Up to 10% to 15% of PTLD present with central nervous system involvement. A patient may present with lymphadenopathy or palpable masses. Extranodal involvement is common. Given the nonspecific nature of clinical presentation, the diagnosis of PTLD requires a high index of suspicion.

6. What are the different types of PTLD?

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  Benign polyclonal lymphoproliferation

  
  
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  Polyclonal lymphoproliferation with malignant transformation

  
  
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  Monoclonal lymphoproliferation with malignant transformation (Hanson et al., 1996)

7. What are the treatment options for various PTLDs?

The treatment and management of PTLD is varied. Treatment is often dictated by the cell type and stage of the lymphoproliferative process. Treatment strategies are individualized and can include:

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  Reduction of immunosuppression

  
  
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  Antiviral therapy

  
  
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  Chemotherapy

  
  
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  Intravenous immunoglobulin (IVIG)

  
  
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  Surgical resection

  
  
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  Radiation

  
  
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  Interferon therapy

  
  
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  Anti-CD20 monoclonal antibody therapies