Skin cancer in heart transplant recipients - Risk factor analysis and relevance of immunosuppressive therapy

Background-The frequency of skin tumors of all types and specifically of sq uamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial. Methods and Results-We studied 300 patients (age 49+/-15 years, 258 men, me an follow-up 4.6 years, follow-up range 1 month to 12 years) who were recei ving standard double (cyclosporin plus azathiopline) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society fo r Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, an d 4=6) and used as an indirect marker of the level of immunosuppression. Mu ltivariate analysis (Cox regression) included age at HT, sex, skin type, fi rst-year rejection score, presence of warts and solar keratosis, lifetime s unlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (P=0.03, RR=5.3), skin type II (P=0.05, RR=2.6), rejection score of 19 (P=0 .003, RR=5.7), solar keratosis (P=0.001, RR=6.9), and lifetime sunlight exp osure of >30 000 hours (P=0.0003, RR=7.6) were risk factors for SCC. Conclusions-Older age at HT, light skin type, solar keratosis, greater sunl ight exposure, and high rejection score in the first year were independentl y associated with an increased risk of SCC, The progressive increase in can cer frequency during follow-up and the association with high rejection scor es suggest that both the length and level of immunosuppression may be relev ant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.