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BACKGROUND There is little current insight into the natural history of childhood leukaemia or the timing of relevant mutational events. TEL-AML1 gene fusion due to chromosomal translocation is frequently seen in the common form of childhood acute lymphoblastic leukaemia. We investigated whether this abnormality arises prenatally. METHODS We identified, by(More)
Using proteins in a therapeutic context often requires engineering to modify functionality and enhance efficacy. We have previously reported that the therapeutic antileukemic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cysteine proteases. In the present study, we successfully engineered L-asparaginase to resist(More)
Currently over 95% of children who are diagnosed with Acute Lym-phoblastic Leukaemia in the UK are enrolled into Medical Research Council trials. The trial protocol specifies that following initial treatment there is a 2-3 year maintenance period during which drug dosage decisions are made weekly according to a set of pre-defined rules. These rules are(More)
We focus on the problem of prediction with confidence and describe a recently developed learning algorithm called transductive confidence machine for making qualified region predictions. Its main advantage, in comparison with other classifiers, is that it is well-calibrated, with number of prediction errors strictly controlled by a given predefined(More)
BACKGROUND Adenovirus infections are associated with significant rates of morbidity and mortality among children after bone marrow transplantation (BMT). Many transplantation units use molecular virological methods, such as polymerase chain reaction (PCR), for surveillance for adenovirus infection and give preemptive antiviral therapy to children with(More)
BACKGROUND Although survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades, the outcome of those who relapse has remained static. We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens. METHODS This open-label randomised trial was undertaken in(More)
l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in(More)
The treatment of a child with Acute Lymphoblastic Leukaemia (ALL) requires the collaboration of multiple providers across different organisations. We describe the implementation of a clinical information system for supporting collaborative care in the management of children with ALL. The system integrates the provision of patient data and clinical(More)
The duration of symptoms before diagnosis (lag time) was defined for 184 of 236 children diagnosed as having a malignancy at the Royal The natural logarithm of the lag time was correlated with age, gender, diagnostic group, white cell count in acute leukaemia, clinical stage of disease in solid tumours, and event free survival. Age was significantly(More)