Malignancy in transplantation

Causes

• Reduced immune surveillance
  • T-cell function suppression
• DNA damage and impaired repair
  • Anti-metabolites cause DNA damage and impair repair
• Increased viral oncogenesis
  • T-cell function that normally detects and eliminates virus infected cells is inhibited
• Increase UV-B risk
  • Reduced immune response to UV damaged cells

Overview

Caused by a combination of impaired immune activity against viruses, impaired immune-surveillance of neoplastic cells, DNA damage and disruption of DNA repair mechanisms, and upregulation of cytokines that can promote tumour progression.

• Increased risk of developing most types of malignancy
  • Risk particularly high for those types of tumour in which viral infection plays an aetiological role
• Cutaneous SCC most common skin cancer
  • BCC and Melanoma also higher than in general population
  • Risk rises with age and with exposure to sunlight
  • 50% of transplant pts will develop a skin malignancy within 20 years
    • Patients must be warned of this risk before they undergo transplantation
    • Advised to take precautions to protect their skin from excessive sunlight
  • Should undergo a regular review of their skin
  • Treat malignant lesions promptly and aggressively
• Post-Transplant Lymphoproliferative Disorder (PTLD)
  • Abnormal proliferation of B-Lymphocytes, usually in response to EBV
  • Presents in a variety of ways
    • Infectious mononucleosis-type illness
    • Lymphadenopathy
  • Occurs in around 1–3% of Kidney and Liver transplants
    • Incidence considerably higher in children
  • Biggest risk is aggressive immunosuppression
  • Serious condition - mortality up to 50%
  • If identified early:
    • Reduction or cessation of immunosuppressive therapy may cause disease regression and result in cure
  • Chemo often given and anti-viral therapy, surgery and radiotherapy may also have a role
• Kaposi sarcoma: 300x increased risk
  • Although still very uncommon

Prevention

• Avoid carcinogens
  • This is particularly true for skin cancers and avoidance of UV radiation.
  • Smoking
  • Alcohol
• Avoid excessive immunosuppression
  • There is a dose response for all transplant patients and all immunosuppressive therapies
• Screening
  • Viral
    • Screen all donors and recipients of HSV8, EBV to minimize Karposi’s and PTLD respectively.
      • If positive recipient, measure EBV titres and adjust immunosuppression if increasing
  • Screen recipients regularly for malignancy o Skin check: 6-12m o Cervical smear and gynaecology assessment: regularly o Anogenital examination: regularly o Breast and Bowel: as per general population o Renal tract: annual MSU o Prostate: PSA and DRE annually >50 yo

Management

• Tumours should be managed based on their type and stage • Main principles are to:

1. Reduce immunosuppression, particularly calcineurins (which increase risk of Kaposi’s Sarcoma especially)
2. Consider conversion to mTOR inhibitor (Sirolimus). o Sirolimus has been shown to induce complete regression of Kaposi’s Sarcoma