World first genome wide study of which people make the best stem cell donors

Scientists do not currently know why some people are able to give far more than others. The more stem cells in a donation, the more likely the stem cell transplant will successfully save or improve a life.

The GeSTy study will use genetic testing to examine the DNA of frozen samples from up to 5,000 past donors held by the NHS Blood and Transplant registry and the Anthony Nolan registry, to try and identify which genes influence how many stem cells people are able to donate. (1) GeSTy is the first genome wide study of stem cell donor yields.

The results should enable doctors to develop a scoring system to make better choices about which people should be selected to donate. High stem cell yields are associated with faster recovery times and better patient outcomes. (2)(3)

The study is not focused on particular genes identified in advance. It will use a technique called genome wide association analysis so that scientists can look for the 'signals' of any genes that are associated with higher yields. (4)

Donor stem cell yields can vary 40-fold. (5) The existing research shows factors such as age, sex, weight, and ethnicity predict stem cell yield to some degree. (6)

For example, bigger people, and men, generally give higher yields. But these factors only explain about 25% of the variation. The GeSty study is aimed at finding out which genes influence the other 75% of variation.

The study should also help make sure donors are picked who can at least meet the minimum stem cell threshold. Around 40% of donors do not give a high enough stem cell yield on the first donation. They may be asked to go through more injections of a growth factor to boost stem cell donation or to donate bone marrow, which requires surgery and general anaesthetic. Five per cent of people are not able give a high enough yield at all.

The study is estimated to complete by 2027. The leads are Dr James Griffin, Medical Director of Cell, Apheresis and Gene Therapy Therapies at NHS Blood and Transplant, Dr Andrew Mumford, Professor of Haematology at the University of Bristol, and Dr Rachel Peck, Clinical Research Fellow Cell at NHSBT. The study is funded by NHS Blood and Transplant.

Francis Judd, aged 26, is an example of the sort of donor the study wants to find.

His stem cell donation last June contained the third highest number of stem cells of any donor through NHS Blood and Transplant during 2023.

His donation of 1.1 billion stem cells was around twice as many stem cells than the average donor to NHSBT that year and around 20 times more than the person whose donation contained the fewest stem cells.

Francis, a software engineer living in Clapham, said: "It was the third time I'd been called as a potential match and the way I thought about it, it would be of negligible impact on me but someone else really needs it, so why not do it.

"It was a cool thing to do.

"I am glad I was able to donate a lot of stem cells for whoever needed them. It does sound like a beneficial study because the people who receive stem cells are very vulnerable and need to have good treatment."

Dr Rachel Peck, Clinical Research Fellow at NHS Blood and Transplant, one of the study leads, said: "NHS Blood and Transplant is carrying out this study because there can be big stem yield variations between fairly identical people. We think genes are likely to play a big part in that. There are around 7-8 genes we suspect play a part but the study will be 'gene agnostic'; we'll see if there are effects from genes we have not studied before. It's likely to be your combination of genes rather than one or two which make the difference and the more stem cells you can give, the more likely the transplant will be a success."

Dr James Griffin, Medical Director of Cell, Apheresis and Gene Therapies at NHS Blood and Transplant, one of the study leads, said: "This is world leading research led by NHS Blood and Transplant in collaboration with Anthony Nolan and the University of Bristol, the first genome wide study of stem cell donor yields. The data can be translated into new ways to prioritise donors and save and improve even more lives. The wider use of genomic matching at NHSBT will improve patient and donor matching, which will particularly help reduce health inequalities."

Dr Andrew Mumford, Professor of Haematology at the University of Bristol, one of the study leads, said: "It's a privilege to have helped with the technical design of this study which recognises the importance of the genetic characteristics of donors in determining stem cell yield. The study findings will increase the repertoire of genetic factors that are increasingly at to forefront of how we deliver care within the NHS."