When the ‘blood factory’ in the bone marrow does not work properly, it is replaced with stem cells from a donor. The DNA of transplanted stem cells can be unstable – but the exact effect of stem cell transplantation on DNA was not yet known.
Safety of bone marrow transplants
Researchers in the Van Boxtel group at the Princess Máxima Center examined the entire DNA of blood stem cells in 9 patients who had undergone a stem cell transplant. They compared the amount of changes in the DNA of these cells with those in blood stem cells from healthy donors.
They found that the majority of transplanted blood stem cells did not contain a higher number of mutations than those of healthy donors. That is important evidence for the safety of stem cell transplants.
The research was published today (Tuesday) in the journal Cell Stem Cell, and was supported by funders including NWO and the European Research Council.
Unknown ‘scar’ in the DNA
The researchers also found indications that an anti-virus drug could cause DNA changes. In exceptional cases, the drug could even contribute to the development of cancer. More research is now needed to study this further.
In a small number of patients, Van Boxtel’s team, also affiliated with the Oncode Institute, encountered a specific ‘scar’ in the DNA that they had not seen before. The scientists then looked at data from 3,000 patients with cancer that had spread, or blood diseases. They discovered 9 more patients with this DNA scar.
The researchers noticed that all of these patients had been treated with the drug ganciclovir. This is a medicine used to treat serious viral infections in people with a weakened immune system, such as children with leukemia who have had a stem cell transplant.
Mutations in cancer genesBy exposing blood stem cells in the laboratory to various antiviral drugs, the researchers saw that ganciclovir was able to cause the scar in the DNA. The drug also led to changes in genes known to lead to cancer.
To make a comparison, the team tested another anti-virus drug, foscarnet. When tested on cells in the lab, this drug did not cause additional DNA changes and the DNA scar. Like ganciclovir, foscarnet is used to treat viral infections after stem cell transplantation. However, it is not tolerated long-term by most patients, due to side effects in the kidneys.
Further research looking at larger groups of patients and in the longer term is now needed to better understand the effect of ganciclovir on DNA.
Dr. Ruben van Boxtel, principal investigator at the Princess Máxima Center and leader of the study, says:
‘Thanks to new techniques to unravel the full genetic make-up of tumors, we have found strong evidence for the safety of stem cell transplants.
‘We also saw that an antiviral drug leaves a scar in the DNA of the donor stem cells. The exact effect of the scar is still unclear. In what way these DNA changes can lead to cancer, and how strong that effect is, still needs to be investigated.
‘There are currently more than 30 of these types of antiviral drugs on the market, which are used to fight infections with various viruses. Our new study underscores the need to investigate which of these agents are or aren’t harmful to the DNA of our cells.’
Dr. Mirjam Belderbos, pediatric oncologist and principal investigator at the Princess Máxima Center for Pediatric Oncology, and co-author of the study, says:
‘It is reassuring to know that stem cell transplantation, a treatment for children and adults with leukemia and other blood disorders, usually leaves no scars in the DNA of the transplanted stem cells.
‘Thanks to this research, we now know that treatment with ganciclovir after stem cell transplantation could have long-term side effects in some patients. It is important to further investigate how often ganciclovir leads to DNA changes, and in which patients.
‘Viral infections after a stem cell transplant can be serious and sometimes life-threatening. There is currently no good alternative to ganciclovir. We’re keeping a close eye on developments in the field of new medicines.’
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