A child on the gene therapy programme at Great Ormond Street Hospital for Children NHS Trust has developed leukaemia, two years after treatment.
There are high hopes for gene therapy
The child had been successfully treated for X-SCID, a condition which leaves the patient unable to fight off infection and disease.
What is X-SCID?
It stands for X-linked Severe Combined Immunodeficiency, and is also known as "bubble boy" disease.
Children born with the condition, which is caused by a single mutated gene, have no immune system
They must live in sterile conditions or risk picking up a life-threatening infection.
Why was gene therapy developed for X-SCID?
X-SCID is fatal unless treated. The conventional treatment is bone marrow transplantation, which has excellent results with a full matched donor, but less satisfactory results with a poorer match.
Only one third of X-SCID patients will have a fully matched donor.
Bone marrow transplantation involves powerful chemotherapy and up to 20% of children transplanted with a less than full match die.
Gene therapy has therefore been a highly valuable treatment option for this group of children.
How does gene therapy work?
In gene therapy, a working copy of the defective gene is placed in the child's own bone marrow cells and these are then returned to the child.
The gene is placed in the cells using a vector, a modified virus.
Modified cells grow rapidly and ensure that the child's immune function returns, sometimes completely.
Why is there a risk of leukaemia?
A similar X-SCID trial in Paris led to a number of children developing leukaemia (four cases from 11 treated).
Three were treated and recovered, one died.
There is no doubt in the Paris cases that the leukaemia was caused by the gene therapy, where the introduced gene was implanted next to, and switched on, an oncogene (a cancer causing gene).
The three other children are in remission from leukaemia, their immune systems are now working again, and they are doing very well.
Great Ormond Street has conducted a number of molecular tests and says it can demonstrate that the case of leukaemia on its trial was also caused by the gene therapy.
The actual mechanism is similar to the cases in Paris and further work is ongoing.
Did the families know the risks?
Yes. Families are carefully counselled about the possible risks, and since the first Paris case, this has included discussion of the possibility of leukaemia.
Great Ormond Street said it was "extremely thorough" in seeking fully informed consent and all the families have been aware of the risk before entering the study.
In every case, the hospital required the approval of the regulator before treating a patient and a number of children including the present case received independent counselling from an independent specialist.
What are the prospects for the children who get leukaemia?
Leukaemia is a very serious illness but can be treated and success rates now exceed 80%.
Is it worth persevering with gene therapy?
Great Ormond Street argues that taking its results and Paris' together, present indications are that gene therapy is still safer and less intrusive than the conventional treatment, for those children without a good bone marrow donor match.
The hospital has pledged to continue to try to minimise risks to patients through protocols and better design.
The current gene therapy treatment for X-SCID is being replaced by a new vector which has been designed to reduce the risk.
There are no plans to use our old vector to treat future children.