Study shows higher cancer risk of pre-transplant therapy

Sep 5 2013

Adrian Hibberd, left, and Paul Trevillian.

Transplant research experts Adrian Hibberd, left, and Paul Trevillian.

The use of immunosuppression therapy prior to kidney transplantation elevates the risk of all cancers – particularly cervical, breast and urinary tract cancers as well as non-Hodgkin lymphoma – a Newcastle-based clinical study has shown.

It follows a statistical analysis of almost 6000 renal transplant patients recorded on the Australian and New Zealand Dialysis and Transplantation Registry (ANZDATA) since 1982, compared with incidence data from the Australian Institute of Health and Welfare’s National Cancer Registry.

“Clinicians have known for some time that the immunosuppression used to prevent organ rejection can reduce a patient’s immunity to cancers but it wasn’t appreciated until this study that the drugs administered beforehand bring a statistically-significant risk as well in the post-transplant period,” Professor Adrian Hibberd, Emeritus Consultant in Transplantation at Hunter New England Health (HNEH), said.

“Australia was uniquely placed to conduct the research because of the comprehensive national databases available and we believe the results will have real translational benefits.”

HNEH Director of Transplantation Dr Paul Trevillian said that about 10 per cent of transplant patients received early immunosuppressive therapy to combat diseases causing their kidney failure.

“It’s a double hit (of immunosuppression) for some people, and the cancer effect of the preliminary dose wasn’t really understood,” Dr Trevillian explained.

“We can now inform patients in this subgroup of the associated risk and will look at every way possible to tailor their treatment. There’s sometimes a point where immunosuppression stops yielding any benefit and it would be appropriate to stop the therapy in light of the cancer risk.

“We have also pioneered a program in this unit whereby we measure antibodies in the blood and do biopsies to look for early signals of rejection. If these two tests prove that rejection risk is low we consider early reduction of immunosuppression.”

The research team’s ultimate goal is to conduct genetic testing to determine which patients will be fully tolerant to their graft without requiring lifelong immunosuppression.

“Up to a third of people don’t need immunosuppression after their transplant, but we don’t know which third at the moment,” Dr Trevillian said.

Professor Hibberd believes there is a further need to explore how transplant patients can be immunised against cancer.

“It has already been heralded by the use of Gardasil, a vaccine used to prevent certain types of HPVs (human papillomavirus) that cause cervical cancer, and we need to look at how those technologies can be applied to transplantations,” he said.

“In the case of breast cancer, when immunosuppression is administered beforehand the risk is significantly increased whereas it’s not when taken post-transplant only. Hopefully our study will be a stimulant to developing further immunisation against HPVs.”

The study titled ‘Effect of Immunosuppression for Primary Renal Disease on the Risk of Cancer in Subsequent Renal Transplantation’ was published earlier this year in the international journal Transplantation and was recently abstracted in the New York-based World Biomedical Frontiers, which collates international papers based on originality and scientific impact factor.

The biostatisticians involved with the study were John Wlodarczyk and Dante Kemp.

Currently, around 700 transplant operations are performed annually in Australia, with the John Hunter Hospital team in Newcastle averaging one per week and having the highest donor rate of any hospital in NSW.

* Kidney recipients from throughout the Hunter Region, along with their family, friends and, in some cases, donors, will be participating in the inaugural Glow Walk on Saturday (September 7) to raise funds for further transplant research. The 2km walk starting at Nobbys Surf Club at 4pm is being staged by the Hunter Transplant Research Foundation (HTRF), with organisers encouraging ’80s-style fluoro fashion.

* Professor Adrian Hibberd and Dr Paul Trevillian are co-founders of the HTRF along with. HTRF is a subcommittee of the HMRI Foundation. HMRI is a partnership between the University of Newcastle, Hunter New England Health and the community.