Mutations in Donor Stem Cells Could Harm the Health of Patients with Cancer, Study Finds

Rare mutations in donor stem cells may cause health problems for patients with cancer who receive them, even though these mutations didn’t affect the health of the donor, according to study findings published in Science Translational Medicine.

Researchers from Washington University School of Medicine in St. Louis discovered this while analyzing bone marrow samples from 25 adult patients with acute myeloid leukemia (AML).

Heart damage, graft-versus-host disease and, potentially, new leukemias, are the risks associated with these mutations.

“There have been suspicions that genetic errors in donor stem cells may be causing problems in cancer patients, but until now we didn’t have a way to identify them because they are so rare,” senior author Dr. Todd E. Druley, an associate professor of pediatrics, said in a news release. “This study raises concerns that even young, healthy donors’ blood stem cells may have harmful mutations and provides strong evidence that we need to explore the potential effects of these mutations further.”

The harmful mutations were found in surprisingly young donors, explained the researchers. Healthy donors ranged in age from 20 to 58, with an average age of 26 years old. Interestingly, the mutations, because they are so rare, were not detected using usual genome sequencing techniques.

In the study, the researchers sequenced 80 genes that are associated with AML using a technique called error-corrected sequencing. They found at least one harmful genetic mutation in 11 of the 25 donors. Eighty-four percent of the mutations identified in the donor samples were potentially harmful and 100% of the harmful mutations were found in the recipients — the most common mutation seen is a gene associated with heart disease.

“We didn’t expect this many young, healthy donors to have these types of mutations,” Druley said. “We also didn’t expect 100% of the harmful mutations to be engrafted into the recipients. That was striking.”

These harmful mutations persisted over time, and many increased in frequency, explained the researchers.

In addition, 75% of patients who received at least one harmful mutation developed chronic graft-versus-host disease. In patients who didn’t receive a mutation, 50% developed the condition. Graft-versus-host disease either acute or chronic, can occur in patients who receive an allogeneic transplant, which consists of donor stems cells versus a patient’s own stem cells.

The researchers plan to examine the mutations in a larger study to answer the questions that this study revealed.

“Transplant physicians tend to seek younger donors because we assume this will lead to fewer complications” co-author Dr. Sima T. Bhatt, an assistant professor of pediatrics who treats pediatric patients with blood cancers at Siteman Kids at St. Louis Children’s Hospital and Washington University School of Medicine, said in a news release. “But we now see evidence that even young and healthy donors can have mutations that will have consequences for our patients. We need to understand what those consequences are if we are to find ways to modify them.”