De Novo Malignancy after Heart Transplantation

Abstract

The volume of heart transplants (HTx) has increased over the past decade, with a concurrent improvement in post-transplant survival. De novo malignancies (DNM) are a known morbidity associated with immunosuppression and become particularly relevant as HTx patients are living longer. We therefore sought to characterize the development of DNM post-HTx. We queried the Organ Procurement and Transplantation Network database for adult HTx patients from 1987-2018. Patients diagnosed with a recurrence of a pre-transplant malignancy or squamous or basal cell carcinomas were excluded. Kaplan-Meier analysis was performed to compute annual probabilities of developing DNM. Rates were compared to the general population in the Surveillance, Epidemiology, and End Results (SEER) database with standardized incidence ratios (SIR). Categorical and continuous characteristics were compared using Pearson's chi-squared and two-sample t-test. Amongst 49,491 HTx patients, median follow-up was 6.91 years. A total of 9,165 DNM were diagnosed in 6,383 patients (12.9%) at an average of 8.0 (SD 5.3) years post-HTx. At 1, 3, and 5 years, the probability of developing DNM was 0.7%, 2.8%, and 5.4%, respectively. The most commonly diagnosed DNM were lung (22.3%, n=1,424), prostate (16.4%, n=1,049), and post-transplant lymphoproliferative disease (PTLD)/lymphoma (16.4%, n=1,049). Malignancies had a higher incidence among HTx patients than in the general population (SIRs: overall 3.83, lung 5.3, prostate 2.13, and PTLD/lymphoma 10.4). As compared to patients who did not develop a DNM, those who did were more likely to be male (83.0% vs. 75.8%), have a history of smoking (58.9% vs. 46.3%), and be older (mean age 55.4 vs. 51.3 years) (all p<0.001) (Table 1). The incidence of DNM is fourfold higher among HTx recipients as compared to the general population, particularly in those with additional risk factors such as male sex, smoking history, and older age. Close oncologic surveillance is particularly critical as patients survive longer.