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 leukaemia 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 tumour’ 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.”
About stem cell transplants
A stem cell transplant, also known as a bone marrow transplant, is used to increase the chance of a cure or remission for various types of blood cancers and blood disorders, including leukaemia, lymphoma and myeloma. As a rule, it is not often a first-line treatment – conventional chemotherapy or other treatments tend to be used first.
A stem cell transplant allows the use of high-dose chemotherapy to kill cancerous cells that is more intensive than conventional chemotherapy. This treatment also kills stem cells in the bone marrow that would normally make blood cells, so stem cell transplants allow patients to be given back stem cells, which can then make normal blood cells again.
Stem cells transplants can either be ‘autologous’, where the stem cells come from the patient themselves or ‘allogenic’ – from a relative or unrelated matched donor. While autologous transplants carry fewer side-effects, allogeneic transplants carry the additional benefit of replacing the patient’s immune system with donor white blood cells that are more likely to attack any remaining cancer cells in the patient.
Bloodwise is the UK’s specialist blood cancer research charity dedicated to improving the lives of people living with and beyond blood cancer. The charity, which was formed in 1960, changed its name from Leukaemia & Lymphoma Research in September 2015.
Around 39,000 people of all ages, from children to adults, are diagnosed with blood cancers and related disorders every year in the UK. It is a complex disease area made up of over 100 individual diseases. Some affect thousands of people, such as common forms of leukaemia, lymphoma and myeloma. Others affect only a handful. But together, blood cancers are the fifth most common form of cancer and the third largest cause of cancer death in the UK.
The charity’s research is targeted at understanding more about blood cancer, finding causes, improving diagnosis and treatments, and running ground-breaking clinical trials for patients. The charity champions patients’ needs by influencing relevant decision makers and influencers, and seeking to raise awareness of the issues faced by patients. Their patient services provide information, support and assistance to patients at every stage of their journey. For more information visit www.bloodwise.org.uk
King’s College London
King’s College London is one of the top 25 universities in the world (2017/18 QS World University Rankings) and among the oldest in England. King’s has more than 29,600 students (of whom nearly 11,700 are graduate students) from some 150 countries worldwide, and some 8,000 staff.
King’s has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF), eighty-four per cent of research at King’s was deemed ‘world-leading’ or ‘internationally excellent’ (3* and 4*).
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