A new procedure that can prevent the potentially lethal side effects of stem cell transplants is a step closer to helping more patients with blood cancers after a breakthrough in understanding of the key mechanism that makes it work.
The research, by scientists based at King’s College London, was funded by the blood cancer research charity Bloodwise, and is published online in the journal Science Translational Medicine.
Stem cell transplantation, also known as bone marrow transplantation, represents the only chance of a cure for some people with leukemia and is given after rounds of intensive chemotherapy, which kill cancer and healthy blood cells in the patient. Blood stem cells from donor bone marrow, sometimes known as a ‘graft’, then provide the patient with a new healthy blood supply, including a new immune system that can hunt down and kill remaining cancer cells – a process called a ‘graft versus tumor’ response.
Although stem cell transplants can be life-saving, many people experience a potentially lethal complication, in which the donor white blood cells also attack the patient’s healthy cells and tissues – a phenomenon known as ‘graft versus host disease’ or ‘GvHD’.
A new procedure to treat the most severe cases of GvHD, which involves the infusion of rare bone marrow cells called mesenchymal stem cells, has had highly promising results in some patients. Its use has been limited, however, as its effectiveness appears to be entirely unpredictable.
Researchers, led by Professor Francesco Dazzi, showed that the immunosuppressive effect of mesenchymal stem cells only occurs if they die after infusion into the patient. Studying the procedure in mice with GvHD, the scientists found that it is only during ‘apoptosis’, the process of cell death, that mesenchymal stem cells engage with the patient’s immune system and tell it to stop attacking healthy tissue. Accordingly, only patients whose immune systems attack and kill the infused mesenchymal stem cells benefited from a suppressive effect on their GvHD.
The team then showed that mesenchymal stem cells killed in the laboratory just before being infused were just as effective at suppressing GvHD in mice, raising the possibility that the procedure could be made effective for all patients.
Professor Francesco Dazzi, from the Division of Cancer Studies, King’s College London, said:
The side effects of a stem cell transplant can be fatal and this factor is a serious consideration in deciding whether some people are suitable to undergo one. If we can be more confident that we can control these lethal complications in all patients, more people will be able to receive this life saving procedure.
The next step will be to introduce clinical trials for patients with GvHD, either using the procedure only in patients with immune systems capable of killing mesenchymal stem cells, or killing these cells before they are infused into the patient, to see if this does indeed improve the success of treatment.
Over 1,600 people received a bone marrow transplant from a related or unrelated donor in the UK and Ireland in 2016. It is estimated that up to 80% of recipients of a transplant from a donor will experience some degree of GvHD.
Dr. Alasdair Rankin, Director of Research at Bloodwise, said:
For people with blood cancer who can’t benefit from other forms of treatment, stem cell transplants offer a lifeline to a cure. But for too many patients these transplants fail, and some people sadly die in the process. Research to improve the effectiveness of stem cell transplantation is vital and we look forward to seeing these exciting findings tested in people living with blood cancer.