Are cell transplant therapies safe?

Cell therapies, such as stem cell transplants, are becoming a reality for the treatment of diseases ranging from cancer to multiple sclerosis and diabetes. However, since the first blood-forming stem cells (hematopoietic stem cells) were successfully transplanted into people with blood cancers more than 50 years ago, researchers have wondered whether these cells would develop cancer-causing mutations.

Now, a study of long-lived transplant recipients and their donors has revealed that people who receive stem cells from donors do not appear to be at increased risk of developing such mutations.

In research published in the journal Science Translational Medicine , researchers from the University of Washington and the Fred Hutchinson Cancer Center (USA) present new findings on the long-term safety of stem cell transplants.

The study evaluated recipients of long-term hematopoietic transplants, some of which were performed more than 40 years ago, and concluded that these patients do not show a significant increase in cancer-related genetic mutations compared to non-transplant recipients. These results offer reassurance to patients who have undergone or are considering these therapies to treat hematologic cancers and other blood disorders.

Since blood-forming stem cells began to be used in the 1960s to treat certain blood cancers and bone marrow diseases, the scientific community has been concerned about whether these cells could develop cancerous mutations when transplanted.

These stem cells, found in bone marrow, have the ability to generate different types of blood cells and have helped save the lives of hundreds of thousands of people worldwide. However, the transplant process, which requires replacing all of the patient's hematopoietic stem cells with those of a healthy donor, places significant stress on the body and has raised concerns about a possible increased risk of cancer.

Masumi Ueda Oshima 's team in Seattle conducted an exhaustive study of 32 individuals, 16 donor-recipient pairs who received transplants between 7 and 46 years earlier. Using advanced genetic sequencing techniques, they investigated mutations in genes associated with blood cancers to determine whether transplantation accelerated their development in recipients.

The results revealed that, although both donors and recipients presented some genetic mutations, the frequency of these mutations remained low, around one per million base pairs sequenced. Furthermore, the study observed that the rate of mutations remained stable over time: in donors, the mutation rate was 2% per year, while in recipients it was 2.6%.

A parallel study by Spencer Chapman of the Barts Cancer Institute in London, published in April 2023, examined 10 stem cell recipients who had received transplants from their siblings between 9 and 31 years earlier. Using whole genome sequencing, the researchers found that the recipients' cells had aged only 1.5 years more than the donors', a minimal change consistent with Ueda Oshima's findings.

Chapman said the finding was " surprising and reassuring ," as it indicates that transplant recipients do not develop new mutations at a high rate or have a greater predisposition to blood cancer compared to donors.

Alejo Rodríguez-Fraticelli , a stem cell biologist at the Barcelona Institute for Research in Biomedicine , also highlighted the study’s results, but noted the need for research in larger groups to confirm the findings. Speaking to the journal Nature , Rodríguez-Fraticelli said that although the study’s participant numbers were limited, the data was “encouraging news” for the medical community and for patients who rely on stem cell transplants or blood-based gene therapies to treat diseases such as cancer and sickle cell disease.

Both studies highlight that the hematopoietic system has a remarkable regenerative capacity that allows stem cells to maintain their function with genetic stability for years after transplantation.

Another study recently published in The New England Journal of Medicine and conducted on more than 700 patients treated at Stanford Medicine showed that the risk of developing secondary blood cancers after CAR T cell therapy is low.

CAR-T cell therapy is a cell-based cancer treatment that revolutionized the treatment of untreatable blood cancers in 2017. But in November 2023, the U.S. Food and Drug Administration (FDA) issued a warning about the risk of secondary cancers, particularly blood cancers, that may be associated with this therapy. The warning was preceded by reports of patients diagnosed with T-cell cancers unrelated to the cancer for which they had been treated.

Although the FDA warned in 2023 about possible risks of secondary cancers, especially T-cell cancers, follow-up of 724 patients since 2016 revealed that only 6.5% developed a new blood cancer in the three years following treatment. Of the 14 reported cases, only one was a T-cell lymphoma that could be related to the therapy, although further analysis ruled this out. In this single fatal case, researchers attributed the tumor development to immunosuppression caused by the therapy, allowing undetected preexisting cancer cells to grow.

Since the FDA issued a warning in November 2023 about the risk of secondary cancers unrelated to the original tumor in treated patients, other drug agencies began scrutinizing its treatments. In June 2024 , the Spanish Drug Agency reported that, after examining patients treated with this cell therapy, it had identified only 38 cases of secondary malignant tumors among the 42,500 patients who had received CAR-T therapy.

According to Dr. Ueda Oshima, the fact that the mutations remain stable for so long confirms the "depth of regenerative capacity" of these cells, opening up new insights into cellular aging and the long-term safety of these therapies.

For the medical community, these discoveries represent a major advance in the understanding of cell therapies and offer new hope for those facing blood diseases or genetic disorders.

With the increasing use of stem cell transplants in children and young adults, these findings underscore the safety of the therapy and offer confidence that transplanted cells can provide lifelong benefits without significantly increasing the risks of cancer-related genetic mutations.