Leukaemia
MRC-funded trials in childhood leukaemia have led to massive improvements in survival, so that four in five children with leukaemia now recover from the disease, compared with only one in five 25 years ago.
MRC studies have had a major influence on the treatment of children with acute lymphoblastic leukaemia (ALL), a cancer of blood cells. Progress has been made as a result of many gradual improvements in treatment for the disease, achieved through a series of clinical trials aimed at finding the best therapy. This has led to a considerable improvement in survival. The trials have tested drugs that not only treat the cancer, but also treat the symptoms and side-effects, improving quality of life for children with the disease.
Professor Ian MacLennan, at the University of Birmingham, said in the Wellcome Trust’s ‘Witness seminar’ in 20011:
“The MRC trials, particularly those on the acute leukaemias, have been extraordinarily successful… I do not think one can underestimate the educational role that the MRC’s trials have had in increasing the standards of the treatment in the UK and bringing forward new treatments.”
Increase in survival
ALL is by far the most common type of leukaemia in children and accounts for around a quarter of all childhood cancers. Around 380 UK children are diagnosed with ALL every year. This means that about 230 children who would have died each year now survive because of the improvements in their treatment.
The discovery of substances with anti-leukaemia properties began in the 1940s. During the following decade, the MRC took an active role in leukaemia research. In 1955, the MRC established the first multicentre randomised controlled trial (RCT) for ALL, which was necessary because marginal differences in survival could be detected only by studying large numbers of people.
Ongoing trials
In the 1970s, the MRC formed the Leukaemia Steering Committee to encourage collaboration between all hospitals and doctors across the UK that were researching and treating childhood ALL. This enabled the MRC to carry out an ongoing series of ‘rolling’ clinical trials, which continue to this day. These trials are set up so that the most effective treatment in a study is then compared with a potential new treatment in the next study. The Clinical Trial Service Unit at the University of Oxford, funded by the MRC, has been responsible for running the majority of these trials.
The proportion of eligible patients with cancer that join trials is usually well under 10 per cent, and often only one or two per cent of patients with certain cancers join trials. Recruitment to the leukaemia trials, however, increased from 40 per cent of children with ALL by 1971, to 82 per cent by 1984 and over 90 per cent today2. These children have been receiving either the best therapy currently available or an experimental treatment that may offer even more benefits.
The importance of care
Dramatic improvements in the rate of survival started to occur in the 1980s and, by the 1990s, the survival rate in children increased to 80 per cent. Many of the improvements were due to better intensive care – the MRC made funds available for improved nursing care of leukaemia patients in trials.
Sir Alan Craft, Professor of Child Health at the University of Newcastle, said:
“I think the most important thing was the organisation of care as much as the clinical trials… The MRC leukaemia trials are always being held up as a model of how to do it, well, they are, but it’s more about organisation of care than doing the clinical trials”. The leukaemia trials have helped with methodology issues for other areas.
Personalised treatments
In recent years, and because survival has increased so dramatically, the focus of MRC childhood leukaemia trials has shifted to tailoring curative treatments according to the patients’ profile in order to reduce exposure to the side-effects caused by many treatments. A quarter of children initially fail to respond to chemotherapy and need further treatment, which can be very toxic and expensive. So MRC clinical researchers are now trying to increase the success rate of initial treatment so that the disease is less likely to recur. Some children who are cured may develop treatment toxicity-related problems in later life. MRC scientists are therefore also trying to identify patients who are likely to respond to lower doses of drugs, to minimise their exposure to toxic drugs.
Adult leukaemia trials, supported by the MRC, have been running alongside the children’s trials. Several randomised trials have compared treatment or treatment strategies. For example, currently the role of thalidomide is being evaluated. Stem cell transplants have been found to benefit patients who are at the highest risk.
References
1. Wellcome Witnesses to Twentieth Century Medicine, 15, Leukaemia.
2. Eden et al. (2000). Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980-1997. Medical Research Council Childhood Leukaemia Working Party. Leukemia, 14, 2307.
MRC, September 2006