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Corticosteroids are an essential component of treatment for acute lymphoblastic leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in the maintenance phase of therapy. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system (CNS) compared with prednisolone. Substitution of dexamethasone for prednisolone in the treatment of ALL might, therefore, result in improved event-free and overall survival. Children with newly diagnosed ALL were randomly assigned to receive either dexamethasone or prednisolone in the induction, consolidation (all received dexamethasone in intensification) and continuation phases of treatment. Among 1603 eligible randomized patients, those receiving dexamethasone had half the risk of isolated CNS relapse ( P = 0·0007). Event-free survival was significantly improved with dexamethasone (84·2% vs. 75·6% at 5 years; P = 0·01), with no evidence of differing effects in any subgroup of patients. The use of 6·5 mg/m2 dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk-groups of patients and, despite the increased toxicity, should now be regarded as part of standard therapy for childhood ALL. [ABSTRACT FROM AUTHOR]

In the last 20 years, the survival rate for children with acute lymphoblastic leukaemia (ALL) has markedly improved, largely owing to a decrease in relapses. However, children still die from complications of treatment and these are potentially preventable. We have analysed data from three large consecutive national protocols for ALL from 1980 to 1997 [Medical Research Council United Kingdom ALL (MRC UKALL) trials VIII, X and XI] to compare the incidence and causes of treatment-related deaths (TRD). The percentage of TRD has fallen from 9% to 2% (UKALL VIII to XI), largely as a result of a decrease in fatal infections. Deaths during induction have fallen from 3% to 1%, the main causes of death being bacterial, followed by fungal infection, while other causes, chiefly haemorrhage, have not declined. Remission deaths also decreased from 6% to 1%, particularly those deaths due to measles and pneumocystis carinii. More guidelines for surveillance and treatment of infections have been included within progressively more intensive protocols. Risk factor analysis showed increased TRD in patients with Down's syndrome, high leucocyte count and older age in UKALL XI. In contrast, the introduction of blocks of intensification was not associated with an increased death rate. While improved supportive care has reduced the incidence of TRD, there is still scope for further reduction by prompt treatment of suspected infection. Maintenance of herd immunity remains of vital importance in avoiding deaths from measles. [ABSTRACT FROM AUTHOR]

Results of three consecutive completed UK trials (1980-1997) for childhood lymphoblastic leukaemia are presented. National accrual has progressively increased so that over 90% of all the country's ALL cases were treated on the latest trial reported, UKALLXI. From 1980 to 1990, event-free and overall survival progressively improved, following adoption of an American therapy template and use of two post-remission intensification modules. Since 1990 despite demonstration of the benefit of a third intensification module overall event-free survival (EFS) has not improved further. Survival remains high due to a good retrieval rate especially for those relapsing off treatment after receipt of two intensification pulses. Possible reasons for the plateau in event-free survival (including type and dose of induction steroid, dropping of induction anthracycline, type and dose of asparaginase, gaps early in therapy following intensification, and overall lack of compliance in maintenance) are being explored in the latest protocol ALL '97. Cranial irradiation had been successfully replaced by a long course of intrathecal methotrexate injections for the majority of patients. Age (<1 year >10 years) sex (male) and white count >50 x 10(9)/l plus slow initial bone marrow clearance were consistently the most important independent prognostic indicators during this time period. Rome/NCI criteria accurately predict standard and high-risk groups for B cell lineage, but not consistently for T cell disease. This international collaborative venture might help us to define those truly at highest risk, and how we can optimise therapy for specific subgroups including T-ALL and those with unfavourable cytogenetics. [ABSTRACT FROM AUTHOR]

The article discusses about the misconduct of medical directors and surgeons of the Alder hey Hospital. scandal. General Medical Council charged two Bristol surgeons with misconduct on the grounds that they had failed to recognise and act upon their poor outcome results. The Alder hey Hospital was overwhelmed with enquiries from anxious and angry parents. Accounts of post mortem, organ removal, examination and retention, which the medical profession had considered normal practice, rapidly became intertwined with the unprofessional and unacceptable behaviour of one Alder Hey pathologist, Professor van Velzen. The Secretary of State for health then ordered an enquiry, which was conducted by a Queen's Counsel senior trial lawyer, Michael Redfern.

The article comments on the arguments of doctors Angus J. Dawson and Steve M. Yentis on the obligation of British research ethics committees (RECs) to consider the science of research applications because it is related with ethics. It states that RECs must rely on scientific appraisals performed by others to ensure that a study underwent adequate review. It mentions the proposal for a national network of independent research ethics advisers for the National Research Ethics Service (NRES).

Seven hundred fifty-eight unselected children entered into the United Kingdom Medical Research Council acute lymphoblastic leukaemia UKALL VIII Study and Trial were studied for differences in early treatment-related toxicity according to the type of intramuscular L-asparaginase received. Two hundred seventy-five received a product obtained from Escherichia coli and 483 the enzyme from Erwinia chrysanthemi. The E. coli patients had a significantly higher incidence of neurotoxicity, pancreatitis, and life-threatening sepsis (4%, 2%, and 20%, respectively) when compared with the Erwinia group (2%, 0%, and 18%). Severe hypersensitivity was seen in one patient from both groups and the incidence of glucose intolerance was not significantly different. These findings indicate that E. coli asparaginase may be more toxic. With a minimum follow up of 4 1/2 years there is no evidence that either product has made a significantly different contribution to disease-free survival.

Twenty-one children who suffered an acute encephalopathic illness during induction chemotherapy for ALL are described. Convulsions and coma were a major feature of this illness. In the absence of other predisposing factors we feel that the encephalopathy was secondary to drug toxicity. Two children died, and 4 of the surviving children have also died. Modifications of antileukemic therapy because of encephalopathic illness may have had a part to play in the outcome for some of these children. The surviving children appear to be neurologically and developmentally normal.