Research at Birmingham Childrens Hospital.
Your generous donations are being used to help fund children being treated for Leukaemia at Birmingham Childrens Hospital to take part in research that could save their lives. Dr Sarah Lawson advises that the 10 trials we are funding will give a more accurate picture of the cancer's progression and treatment can then be adjusted for the better which will give children a much better chance of survival.
The tests on the 10 children will develop this research which will hopefully become part of the normal clinic practice in 2/3 years time.
Paediatric Leukaemia Research at Birmingham Children’s Hospital
Acute lymphoblastic leukaemia is the commonest childhood cancer, affecting approximately 500 children each year in the United Kingdom i.e. 1 in 25 000 children. It occurs at all ages, in both boys and girls and in all ethnic groups. Improvements in the treatment of childhood acute leukaemia over recent years have resulted in induction of complete remission in most patients. Despite current aggressive therapy over 20% of these patients will relapse, implying that treatment does not kill all leukaemic cells in each patient and that cells surviving are undetectable by routine techniques until florid relapse is present. Better identification of patients at either high or low risk of relapse may allow further individualisation of therapy. This individualisation of therapy has a number of aims. Firstly it may avoid overtreatment in those children with a good prognosis in whom treatment intensity could be reduced. Secondly it may avoid undertreatment in those at higher risk of relapse. The ultimate aim is to improve cure rates and reduce late effects of treatment.
Conventional prognostic factors such as age at presentation and white cell count, albeit useful do not identify all patients at high risk of disease relapse nor those likely to be cured. One method of more accurately assessing an individual patient’s response to treatment and thus identifying both good and poor risk patients is by monitoring ‘minimal residual disease’ (MRD). This is disease present at levels below that that can be detected by morphological (microscope) techniques.
Monitoring of MRD has been shown to be of clinical significance, and this allows further stratification of patients during treatment according to their risk of relapse or cure. The ultimate goal of this stratification is to improve outcome by modifying treatment according to the presence and level of MRD. Reliable techniques for the detection of MRD are therefore needed in order to evaluate the effectiveness of treatment.
Most studies of MRD use molecular techniques that are expensive, time-consuming and of limited availability. Advances in a technique called flow cytometry have led to this technique being used as a method for monitoring MRD in patients with acute leukaemia, although its role and usefulness have not yet been clearly defined. The technology is relatively simple, widely available, sensitive and provides rapid results. It is therefore an attractive method for monitoring disease eradication and detecting early recurrence in large numbers of patients with acute leukaemia.
The Haematology Department at Birmingham Children’s Hospital are currently actively involved in a research project assessing treatment response in children with acute lymphoblastic leukaemia using flow cytometric techniques. This research has the support of the Childhood Leukaemia Working Party and the UK Childhood Leukaemia Research Forum and has appropriate ethical approval.
The two current UK national trials for newly diagnosed and relapsed acute lymphoblastic leukaemia are using molecular analysis of MRD to risk stratify patients during treatment. These trials (ALL 2003, UKALL R3) offer an ideal opportunity to prospectively compare the two techniques of MRD analysis. Such a comparison has not previously been performed.
This research also offers an opportunity to provide rapid results about treatment response to different chemotherapeutic agents and regimens.
The research involves assessing patients for low levels of residual leukaemia in bone marrow samples taken during the course of their treatment. These samples are analysed using multiparameter four colour flow cytometry, which permits detection of up to 1 leukaemic cell in 10 000 normal cells. Prior to analysis the samples are incubated with a panel of monoclonal antibodies designed for each patient’s leukaemia. The red cells are lysed, following which up to 1 million cells are analysed by the flow cytometer. The presence and amount of residual disease is then determined.
We hope that if we can prove that flow cytometric analysis is comparable to molecular analysis of residual disease, that the former technique will be available to all patients with acute lymphoblastic leukaemia and allow further stratification of their treatment according to their treatment response.
The ultimate aim is to improve the cure rate for children with acute lymphoblastic leukaemia, as well as reducing the long-term side effects of chemotherapy.
