Background: Chronic immunosuppression after solid-organ transplantation is a risk factor for cutaneous squamous cell carcinoma (cSCC) development. Certain immunosuppressant drugs, namely azathioprine and calcineurin inhibitors, increase this risk more than others. We investigated incidence of cSCC in a Dutch lung transplant recipient (LTR) cohort and analyzed associated risk factors.
Methods: All LTRs with post-transplant survival of >30 days were included. Data included indication for lung transplantation and duration of medication use. Skin cancer data were extracted from the Dutch nationwide registry of histopathology (PALGA). Uni- and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression analyses.
Results: Five hundred forty-four patients were included with a median survival of 11.05 years. Fifty-two (9.6%) LTRs developed at least one cSCC, with a cumulative incidence of 3.9% and 15.3% after 5 and 10 years, respectively. Multivariate analyses showed that the sequential use of azathioprine and mycophenolate mofetil (MMF), both at for least 1 year, was associated with a lower risk of developing cSCC (hazard ratio [HR] 0.24; 95% confidence interval [CI] 0.10 to 0.56) compared with azathioprine use only. Furthermore, age at transplantation (HR 3.42; 95% CI 1.33 to 8.79), male gender (HR 1.75; 95% CI 1.00 to 3.05), previous skin cancer (HR 4.75; 95% CI 1.14 to 19.76), and history of smoking (HR 3.30; 95% CI 1.69 to 6.44) were associated with increased risk of developing cSCC in univariate analyses.
Conclusions: Apart from known risk factors, we found that switching from azathioprine to MMF is associated with reduced incidence of cSCC in LTR, prompting a discussion of whether switching azathioprine to MMF should be considered in high-risk patients.

Additional Metadata
Keywords azathioprine, lung transplantation, mycophenolate mofetil, skin cancer, switching
Persistent URL dx.doi.org/10.1016/j.healun.2018.03.012, hdl.handle.net/1765/106086
Journal The Journal of Heart and Lung Transplantation
Citation
Vos, M. (Martin), Plasmeijer, E.I, van Bemmel, B.C. (Barbara C.), van der Bij, W, Klaver, N.S. (Nina S.), Erasmus, M.E. (Michiel E.), … Rácz, E. (2018). Azathioprine to mycophenolate mofetil transition and risk of squamous cell carcinoma after lung transplantation. The Journal of Heart and Lung Transplantation. doi:10.1016/j.healun.2018.03.012