Does stem cell transplant bring changes in DNA ?

According to a new study, stem cells do not cause changes in DNA of the donor cells. Researchers also found proof that changes in DNA maybe caused by antivirus drugs. Also in some cases, the drugs might lead to cancer formation. Hence, much more research is now needed for further study. Stem cell transplant is an important cure for treating children with leukemia. Although, the exact effect of stem cell transplant on DNA is still not known, but it could make DNA unstable.

Researchers in the group of Ruben van Boxtel, Ph.D., at the Princess Máxima Center for Pediatric Oncology, studied nine patients who had a stem cell transplant. The team looked at the entire DNA of blood stem cells. They compared number of changes in DNA of patients with blood stem cells from healthy donors. Scientist found that most of the transplanted blood stem cell did not had higher number of mutations that those of healthy donors. Therefore, this shows important evidence for the safety of stem cell transplant.

Causes of DNA mutation

Dr. Van Boxtel’s team, found a specific pattern of mutations or scar in DNA of some patients they had not seen before. To study about this mutation, more than 3000 patients with blood disorders or cancer were analyzed. As a result, researchers discovered nine more patients with this DNA scar in their cancer. They observed that all these patients used a drug called ganciclovir. Ganciclovir treat serious viral infection in people with very weak immune system, that had a stem cell transplant. The team also found this DNA mutation in adults with solid tumor, people who had kidney transplant before and then medicated with ganciclovir. Team exposed cultured blood stem cells to ganciclovir in lab, to see if it actually causes changes in DNA. This test showed that the drug did cause scar in DNA they saw earlier. The drug also bring changes in genes known to cause cancer.

Mirjam Belderbos, M.D., Ph.D., pediatric oncologist and principal investigator at the Princess Máxima Center for Pediatric Oncology, said, “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.”

The team examined another antiviral drug, foscarnet. Foscarnet is also use for viral infections after stem cell transplant. However, due to a side effect on kidney, some patients cannot tolerate this drug for longer use. After testing, researchers found that foscarnet did not cause any more changes in DNA or DNA scar that ganciclovir showed.

What future holds?

“There are currently more than 30 of these types of antivirus drugs on the market, that fight infections with various viruses. Our new study stress on the need to investigate which of these are or aren’t harmful to DNA of our cells.”

Long-term research in larger groups of patients is now necessary, to better understand the effect of ganciclovir on DNA. “Thanks to new methods that explains entire genetic make-up of tumors, we discovered that an antiviral drug could have carcinogenic effect. The exact effect of the scar that ganciclovir leaves behind in the DNA is still unclear. In what way these DNA changes can lead to cancer, and how strong the effect is. This has to be investigated,” Dr. Van Boxtel said.

“Virus 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.”