High dose azathioprine increases the risk of malignancy in solid organ transplant recipients — ASN Events
  1. Schedule
  2. Best of the Best Orals - Epidemiology
  3. High dose azathioprine increases the risk of malignancy in solid organ transplant recipients

High dose azathioprine increases the risk of malignancy in solid organ transplant recipients (#55)

Claire Vajdic 1 , Renhua Na 2 , Andrew Grulich 3 , Nicola Meagher 2 , Geoff McCaughan 4 , Anne Keogh 5 , Maarit Laaksonen 1
  1. Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia
  2. Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia
  3. Kirby Institute, University of New South Wales, Sydney, NSW, Australia
  4. Centenary Research Institute, University of Sydney, Sydney, NSW, Australia
  5. Heart Transplant Unit, St Vincent's Hospital Sydney, Sydney, NSW, Australia

Aims

To investigate the association between iatrogenic immunosuppression and risk of non-Hodgkin lymphoma (NHL) and lip cancer.

Methods

We conducted a population-based cohort study of all adult Australian liver, heart and lung transplant recipients 1984-2006 (n=4141). We abstracted risk factor data including immunosuppression at transplantation and regular intervals thereafter from hospital medical records. We ascertained incident lip cancer, early NHL (<1 year after transplant), late NHL (>1 year) and deaths by probabilistic record linkage between transplant registries and the Australian Cancer Database and National Death Index. We estimated multivariable hazard ratios (HR) using the Fine and Gray proportional subdistribution hazards model, accounting for death as a competing risk.

Results

In fully adjusted models, lip cancer (n=58) risk increased with higher mean daily dose of azathioprine (HR 2.28, 95%CI 1.18–4.38), longer duration of immunosuppression (HR 9.86, 95%CI 2.10-46.3 for >5 years versus 1 year), increasing year of age at transplantation (HR 1.14, 95%CI 1.04–1.25), earlier transplant era (HR 8.73, 95%CI 1.11-68.7 for 1984-1994 versus 1998-2006), and history of smoking (HR 2.71, 95%CI 1.09-6.70). Higher mean daily doses of azathioprine also increased the risk of both early (n=29; HR 2.20, 95%CI 1.21-4.01) and late NHL (n=61; HR 1.78, 95%CI 1.12-2.84). Muromonab-CD3 induction therapy was an independent risk factor for early NHL (HR 5.66, 95%CI 1.13-28.3). Risk of late NHL increased with longer duration of immunosuppression (HR 6.20, 95%CI 1.99-19.3 for >5 years versus 1-2 years) and increasing year of age at transplantation (HR 1.12, 95%CI 1.04-1.22). Neither organ type nor any other immunosuppressive agent was independently associated with risk of either malignancy.

Conclusions

With over two-decades of follow-up and detailed longitudinal data on individual immunosuppressive agents, this study provides the first evidence that high doses of azathioprine independently predict risk of lip cancer and NHL. These findings have implications for managing cancer risk in long-term transplant and other immunosuppressed populations and for understanding the pathways to carcinogenesis for these malignancies.

#COSA2015