Doctors at Great Ormond Street Hospital for Children in London have admitted that other children may be at risk after leukaemia was diagnosed in a child on its pioneering gene therapy programme.
The unnamed 3 year old was taking part in a clinical trial treating children for X linked severe combined immunodeficiency (X-SCID), also known as “baby in the bubble syndrome,” in which boys are born with no immune system. Around six to eight children are affected by the condition each year in the United Kingdom.
The trial, which began at Great Ormond Street in 2001 and ended earlier this year, involved 10 children with X-SCID and five with the related ada-SCID. Until now it seemed that most of the children had recovered successfully. However, four of 11 children involved in a similar trial in Paris were found, by 2002, to have gone on to develop leukaemia, one of whom died.
Bobby Gaspar, consultant immunologist on the London programme, admitted that other children taking part in the UK trial remained at risk. “Although we understand the mechanics of how this leukaemia happened, we can’t say at this stage what the frequency will be.”
Professor Gaspar insisted that all the families involved had been carefully counselled about the risks—including that of leukaemia once this became known—and none chose to pull out.
“You have to realise that these children are faced with a fatal disease,” he said, “and they need to have some form of treatment.” The conventional treatment was bone marrow transplantation, but if a full match wasn’t possible the success rate was only 80%.
He said, “The families felt that gene therapy was the safer option in the short term, because they were very unlikely to lose the child as a result of this procedure. They were aware of the leukaemia risk further down the line.”
The gene therapy works by using a vector or modified virus to implant a working copy of the defective gene. But it seems that this can have the effect of switching on oncogenes, cancer causing genes, thus triggering leukaemia.
Scientists have now developed a safer vector that is thought not to affect the oncogenes. Trials using this new treatment are planned for next year, involving centres in Paris, the United States, and Great Ormond Street.
Professor Gaspar said that if the trials were successful, this form of gene therapy could become the standard treatment for children who did not have a fully matched marrow donor. He also expects that a similar approach could be used for many other diseases.
Martin Gore, chairman of the regulatory Gene Therapy Advisory Committee, said that the data from the UK and French trials indicated that the risk of leukaemia might be confined to these two trials. “The more we understand about this specific episode, the better able we will be to develop safer and more effective vectors.”
Fred Kavalier, of the British Society for Human Genetics, said that gene therapy was still at an experimental stage. “The fact that some of the children have gone on to develop leukaemia shows us how difficult it is to repair faulty human genes.”