Abstract
Background: Transplant patients are known to be at increased risk of
developing de novo malignancies (DNM). As heart transplant survival has
increased, DNM represent an obstacle to further improving survival. We
sought to examine the incidence, risk factors, and prognostic factors of
post-transplant DNM. Methods: We studied adult heart transplant
recipients from the Organ Procurement and Transplantation Network
database (1987-2018). Kaplan-Meier survival analysis was performed to
determine annual probabilities of developing DNM, excluding squamous and
basal cell carcinoma. Rates were compared to the general population in
the Surveillance, Epidemiology, and End Results database. Cox
proportional hazards regression was performed to calculate hazard ratios
for risk factors of DNM development, all-cause, and cancer-specific
mortality. Results: Over median follow-up of 6.9 years, 18% of the
49,361 patients developed DNM, which correlated with an incidence rate
3.8 times that of the general population. The most common malignancies
were lung, post-transplant lymphoproliferative disorder, and prostate.
Risk was most increased for female genital, tongue/throat, and renal
cancers. Male gender, older age, smoking history, and impaired renal
function were risk factors for developing DNM, whereas the use of MMF
for immunosuppression was protective. Cigarette use, increasing age, the
use of ATG for induction and calcineurin inhibitors for maintenance were
risk factors for cancer-specific mortality. The development of a DNM
increased the risk of death by 40% (p<0.001). Conclusions:
Heart transplant patients are at increased risk of malignancy
post-transplant, particularly rare cancers. Strict cancer surveillance
and attention to immunosuppressive regimens are critical for further
prolonging post-transplant survival.