Researchers in the Netherlands investigating cancer in children who have received blood stem cell transplants found that the transplant itself does not lead to genetic mutations in transplanted stem cells. However, an anti-viral drug called ganciclovir that is often given to transplant recipients may lead to genetic mutations in transplanted stem cells, which could lead to the development of cancer.
'Thanks to new techniques to unravel the entire genetic make-up of tumours, we discovered that an antiviral drug could have a carcinogenic effect,' said Dr Ruben van Boxtel who led the study, at the Prinses Máxima Center for Paediatric Oncology, Utrecht, Netherlands.
The researchers analysed the DNA of blood cells in nine paediatric patients who had undergone a blood stem cell transplant. They compared the number of changes in the DNA of these cells with those found in the blood stem cells of healthy donors. Their findings, published last week in the journal Cell Stem Cell, indicate that most transplanted stem cells do not display a different number of mutations.
This is important evidence for the safety of blood stem cell transplants, which are necessary for the treatment of some children with leukaemia, and are the most commonly carried out form of stem cell therapy in the world.
However, the team did identify a specific pattern of mutations in the DNA of two stem cell donor recipients. To further investigate this, they developed a machine learning approach to analyse data from over 4011 patients with cancer or blood disorders. This identified the same mutational marker in nine more patients, most of whom it could be determined had been treated with ganciclovir.
To test their theory, researchers treated blood stem cells in the lab with ganciclovir and again observed the same mutations that could lead to cancer.
'The exact effect of the scar that ganciclovir leaves behind in the DNA is still unclear', said Dr van Boxtel. 'In what way these DNA changes can lead to cancer, and how strong that effect is, still needs to be investigated', he added.
Treatment with a different anti-viral drug, foscarnet, did not cause the DNA mutations observed with ganciclovir. Although this drug is also used to treat viral infections after stem cell transplantation, it is not a long-term option owing to damage it can cause to the kidneys.
Further work is now needed to understand the mutational effect of ganciclovir and other anti-virals that may be given to stem cell transplant patients. There is also a need to investigate and develop anti-viral therapies that are not harmful to DNA.