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Do stem-cell transplants increase cancer risk? Long-lived recipients offer clues
Ever since the first blood-forming stem cells were successfully transplanted into people with blood cancers more than 50 years ago, researchers have wondered whether they developed cancer-causing mutations. A unique study1 on the longest-lived transplant recipients and their donors has revealed that people who receive donor stem cells don’t seem to have an increased risk of developing such mutations.
The results are surprising but reassuring, says Michael Spencer Chapman, a haematologist at the Barts Cancer Institute in London.
“It’s fantastic news for people undergoing these therapies,” says Alejo Rodriguez-Fraticelli, a quantitative stem-cell biologist at the Institute for Research in Biomedicine in Barcelona, Spain.
Blood-forming, or ‘haematopoietic’, stem cells are precursor cells that reside in the bone marrow and give rise to all types of blood cell. They have been used to treat hundreds of thousands of people with blood cancers and bone-marrow diseases. The transplants involve depleting a person’s entire blood stem-cell reserves and replacing them with cells from a healthy donor. But researchers have long worried that putting the cells under such pressure could increase the risk of cancer. In rare cases, about 1 in every 1,000 transplants, donor cells develop into a cancer in the recipients.
Fishing expedition
The latest study, published in Science Translational Medicine this week, looked at mutations in specific genes that have been linked to cancer. It was thought that these mutations could give haematopoietic cells a growth advantage in transplant recipients, allowing them to rapidly divide and multiply as the recipient ages and eventually develop into leukaemia.
Some of the first transplants were conducted at the Fred Hutchinson Cancer Center starting in the late 1960s. In 2017, Masumi Ueda Oshima, a clinical researcher who studies post-transplant ageing at the Fred Hutchinson Cancer Center in Seattle, Washington, and her colleagues decided to reach out to the recipients of these transplants, and their donors, to collect samples of their blood and compare how the cells had aged. “It was really a big fishing expedition,” she says.
The team collected blood samples from 32 individuals — 16 donor–recipient pairs — who had received their transplants between 7 and 46 years ago. They used a highly sensitive technique to sequence genes known to acquire mutations associated with bone-marrow cancers.
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doi: https://doi.org/10.1038/d41586-024-03450-x
References
Ueda Oshima, M. et al. Sci. Transl. Med. 16, eado5108 (2024).
Campbell, P. et al. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-2868644/v1 (2023).
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