Analysis of registry data shows that solid organ transplant recipients have an increased risk of malignancy when compared to the general population. Registry data for the UK (Figure 19) illustrates that the cumulative incidence of de novo cancer increases with time since transplantation (Collett et al., 2010).
The standardised incidence ratio (SIR; relative to the general population) for all cancers (excluding non-melanoma skin cancer) in kidney transplant recipients was 2.4 (95% CI, 2.3–2.5), with SIRs for liver, heart and lung transplant recipients being 2.2 (95% CI, 2.0–2.4); 2.5 (95% CI, 2.2–2.7); and 3.6 (95% CI, 3.0–4.4) respectively. Thus, recipients of heart, kidney or liver transplants have more than twice the incidence of cancer compared to the general population. Lung, or combined heart and lung transplant patients, have more than three times the incidence of malignancy (Collett et al., 2010).
For potential kidney transplant patients with a history of malignancy, the recommended period for being cancer-free generally varies from 2 to 5 years, depending on cancer type. However, there is variation in the period recommended between guidelines (Batabyal et al., 2012). The potential for immunosuppression to increase the risk of the cancer returning should be considered for patients waiting for a transplant (Chapman et al., 2013).
The incidence of malignancies mediated by viruses in immunosuppressed transplant patients is relatively high. Post-transplantation lymphoma due to the Epstein-Barr virus affects around 2% of transplant recipients (Watson & Dark, 2012) with non-Hodgkin’s lymphoma having standard incidence ratios (SIRs) in kidney, liver, heart and lung transplant recipients of 12.5, 13.3, 19.8 and 30.0, respectively (Collett et al., 2010). Non-melanoma skin cancer mediated by human papilloma virus (Watson & Dark, 2012) has respective SIRs of 16.6, 6.6, 18.5 and 16.1 (Collett et al., 2010).
Other cancers that are greatly increased in transplanted populations are lip cancer (>10-fold increased risk), Kaposi sarcoma (>50-fold increased risk), and cancers of the anogenital tract (>4-fold increase for vaginal, cervical, vulval, anal, and penile cancers) (Chapman et al., 2013).
A range of cancers developing in transplant recipients have been donor-derived, although the risk is relatively low, being assessed in the UK as 0.03%. Consequently, donors should be screened for the risk of transmission of cancer (Desai & Neuberger, 2014; Chapman et al., 2013).
The incidence of malignancies in transplant patients appears to be related both to the class of immunosuppressive agents used as well as the overall intensity of immunosuppression. For instance, CNI therapy was shown to increase the risk of malignancies following kidney, liver and heart transplantation in a dose-dependent manner. However, it is unclear how much of this effect is a consequence of high-intensity immunosuppression versus specific CNI-related effects. While more data is needed, current recommendations for the management of malignancies in transplantation patients is to reduce the overall burden of immunosuppression and introduce an mTOR inhibitor (De Simone et al., 2017b).
Saber-Moghaddam et al. (2019) reviewed different post-heart transplant maintenance immunosuppressive regimens and their effect on post-heart transplant malignancies, with a focus on mTORs, compared safety against effectiveness, and gathered conclusions based on the review of the literature, which may help clinicians make a better evidence-based decision regarding post-heart transplant maintenance immunosuppressive regimens. Overall, CNI to mTORI conversion in post-HTx maintenance immunosuppressive regimens was associated with a reduced rate of developing malignancy in post-heart transplant patients. Furthermore, nephrotoxicity decreased significantly while using mTORs in combination with lower doses of CNIs. The rejection rate was equivalent to CNI-only regimens. The authors concluded that mTOR-based maintenance immunosuppressive regimens seem to be safe and beneficial when considering efficacy versus adverse effects, and all-cause mortality rates were significantly lower in patients switched to mTORIs when compared to CNI recipients (Saber-Moghaddam et al., 2019).