De-Novo Malignancies Post Heart Transplantation: A Review of the Literature on the Mechanisms, Types, and Causes of the Malignancies

Background: Heart transplantation is a gold standard treatment for patients with end-stage heart disease. With the use of potent immunosuppressive agents and effective post-transplant management of heart transplant recipients, the survival rate of the patients and graft survival have significantly improved. One of the identified complications of heart transplantation is the development of post-transplant malignancy. Objective: To review the literature on De Novo malignancies which develop in heart transplant recipients following cardiac-transplantation. Results: The reported incidence of malignancy following heart transplantation varies hugely between studies. There are conflicting findings with regard to the commonest type of malignancy. Cancers in HT recipients also have slightly differing characteristics compared to their equivalents in the general population. Namely, they have a preponderance for extra-lymphatic sites in PTLD and aggressive nature (SCC). Reported incidence of malignancy following HT varies hugely between studies. There are conflicting findings with regard to the commonest type of malignancy. Some authors estimated that skin cancers were the commonest type followed by PTLD. However, a small study by other authors found PTLD to be most common. Aetiological causes for malignancy seem strongly dependent on the side effects of immunosuppressives which likely act to inhibit the immune system’s response to earlier malignant changes in cells. Viruses such as HPV, EBV, and HHV-8, play an important role in the development of cancer in HT recipients. The mechanisms by which HPV and EBV induce the proliferation of cells are comparatively well understood compared to HHV-8. However, the role of immunosuppressives in this process is not well understood but there is some evidence that withdrawal of immune therapy can induce remission of KS implying that the drugs play a pivotal role. In Kaposis sarcoma Human Herpes Virus 8 is reported to play an important role in the immunosuppressed state. The review discussed the limited evidence which suggests a role for CD-8 T-cells and CD-4 regulatory T-cells in this process.