A multi-institutional study of malignancies after heart transplantation and a comparison with the general United States population

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Background

The purpose of these studies was to determine the incidence and survival of patients with specific malignancies with respect to age and transplant year and to compare the data with the normal non-transplant population.

Methods

Data from 6,211 primary cardiac transplants between July 31, 1993, and December 30, 2008, were collected by 35 institutions participating in the Cardiac Transplant Research Database. Data were compared with information collected by the Surveillance Epidemiology and End Results (SEER) Cancer Statistics Review 1975–2006.

Results

Multivariable analysis showed older age (relative risk [RR], 2.1; p < 0.0001) and earlier transplant year (RR, 1.8; p < 0.0001) were highly significant risk factors. Aggregate malignancy incidence in the modern era (2001 to 2008) did not differ significantly from the normal population, which appeared to be attributable to a lower rate of malignancies other than lung cancer, lymphoma, and melanoma (actual/expected ratio, 0.71). From 2001 to 2008, rates were significantly higher for lung cancer (actual/expected ratio, 1.86; p = 0.006) and lymphoma (actual/expected ratio, 4.3, p < 0.0001) than in the normal population. The highest risk for lymphoma was in younger adults who received transplants at ages 18 to 35 years (actual/expected ratio, 27). The highest risk for lung cancer was in patients who underwent transplantation at ages 55 to 65 years (actual/expected ratio, 28). Once diagnosed with malignancy, subsequent survival at 5 years was 21% for lung cancer and 32% for lymphoma.

Conclusions

The risk of malignancy has markedly declined during a 15-year period such that the aggregate rate of malignancy approached that of the general population in the United States. However, the distribution of malignancies was not the same, with a greater prominence of lung cancer and lymphoproliferative disease.

Section snippets

Patient population

The CTRD database was established in 1990, and collection of malignancy data began in 1993. Between July 1, 1993, and December 31, 2008, 6,211 primary isolated adult heart transplants were performed at 35 centers participating in the CTRD. The median follow-up for 4,288 surviving patients was 5.45 years (range, 0–15.5 years). Methods of data collection, management, and event classification for the CTRD database have been previously described.12, 13, 14, 15, 16, 17

Immunosuppression

Immunosuppression protocols

Occurrence of malignancies over 15 years

Pre-transplant malignancies were documented in 283 of 6,211 primary heart transplants, but post-transplant recurrences of these pre-transplant malignancies were not common (Table 1). The 3 most common pre-transplant malignancies were lymphomas and cancers of the breast and prostate, which collectively constituted 46% of all pre-transplant malignancies.

There were 524 first primary post-transplant malignancies, excluding basal cell and squamous cell skin cancers (Table 2). Figure 1 depicts the

Discussion

Single-center and multi-institutional studies of long-term survival have shown that, among factors limiting long-term survival of cardiac transplant recipients, malignancy is a major contributor.1, 2, 3, 4, 5, 6, 7 In this study, we determined the incidence of malignancies among 6,211 patients at 35 institutions participating in the CTRD from July 1993 to December 31, 2008, a 15-year period. The data were compared with the normal U.S. population as determined by the SEER Cancer Statistics

Disclosure statement

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

References (26)

Cited by (34)

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