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Aims: To examine the clinical and biological features of acute lymphoblastic leukaemia in children with Down's syndrome (DS), to compare their survival with other children, and to determine if entry to trials and survival has improved., Methods: Examination of presenting features and response to treatment in patients treated in two consecutive national trials, MRC UKALL X and XI., Results: The proportion of children with DS was significantly higher in UKALL XI (1.9%) than UKALL X (0.9%). Children with DS tended to be under 10 years and to have the common ALL subtype. Cytogenetic analysis showed that favourable features, such as high hyperdiploidy and t(12;21) were less frequent but also that there was a lack of translocations associated with a poor prognosis. Children with DS showed no increase in risk of relapse at any site but their survival and event free survival were inferior to other children. These results were caused by an increased number of infective deaths during remission (11% compared to 2%). At five years overall survival was 73% in DS children compared with 82% in other children; event free survival was 53% compared to 63% in non-DS children., Conclusions: Entry of children with DS to national trials has increased and survival has improved. However they remain at risk of relapse and also of treatment related mortality. These findings emphasise the need for both intensive chemotherapy and optimal supportive care.

Glomerular filtration rates (GFR) were estimated in 168 children (227 estimates) before treatment for haematological malignancies with high dose, intravenous methotrexate. Clinical management was altered on the basis of GFR in only two cases, both of whom had tumour lysis syndrome. Routine estimations of GFR do not contribute to management.

Objective: To review the clinical features, treatment, and outcome of children in the UK with Down's syndrome and acute myeloid leukaemia (AML)., Design: A retrospective study of 59 children with Down's syndrome and AML presenting between 1987 and 1995. Data were obtained from hospital case notes, trial records, and by questionnaire., Results: The patients were unusually young (median age, 23 months) with a predominance of megakaryoblastic AML. Two of the seven infants who presented with abnormal myelopoesis aged 2 months or younger achieved complete spontaneous remission. Most of the older children with AML (32 of 52) were treated on recognised intensive protocols but 13 received individualised treatment and seven symptomatic treatment alone. Only four received a bone marrow transplant (BMT) in first remission. For the 45 older children who received chemotherapy the overall survival was 55% (median follow up 4.5 years). Patients on individualised protocols had a similar overall survival and toxic death rate but marginally higher relapse rate than those on standard (intensive) protocols. Children with Down's syndrome treated on the national AML 10 trial had a similar overall survival (70% v 59%) at five years to children of comparable age without Down's syndrome: their improved relapse risk (12% v 38%) offset the slight increase in deaths as a result of treatment toxicity (19% v 11%)., Conclusion: Neonates with Down's syndrome and abnormal myelopoesis may achieve spontaneous remission, and older children with Down's syndrome and AML can be treated successfully with intensive chemotherapy, without BMT.

This study compared the prognosis of patients treated for aplastic anaemia at Great Ormond Street Hospital for Children from 1973-88 (group A; n = 38) with a more recent cohort from 1989-96 (group B; n = 37). The two groups were similar in terms of clinical history, age, and severity of aplasia. The main treatment differences included the use of androgen treatment in group A (21 of 38 patients) but not in group B, and the addition of cyclosporin A to immunosuppressive treatment for 14 patients in group B. Actuarial survival at eight years' follow up was significantly better for group B (84%; 95% CI, 68% to 93%) than for group A (45%; 95% CI, 30% to 60%), because of improved outcome for both immunosuppressive treatment (86% v 39%) and bone marrow transplantation (93% v 56%). There was no evidence for late clonal disorders or secondary malignancies in survivors in either group. The prognosis for aplastic anaemia has improved greatly in recent years so that over 80% of children are long term survivors.

There appears to be an increase in imported cases of visceral leishmaniasis in Northern Europe; many are children infected on holiday in the Mediterranean. Making the diagnosis in young children can be difficult especially when an adequate travel history is not obtained at presentation. Two infants with visceral leishmaniasis are presented who were initially felt to have alternative diagnoses and who subsequently responded dramatically to a short course of liposomal amphotericin B (AmBisome).

Over 15 years, 42 children aged 2-14 years were diagnosed as having acquired aplastic anaemia. Adequate clinical details were available for 38 children who were categorised as very severe (n = 13), severe (n = 16), or nonsevere (n = 9) by the modified Camitta criteria. Treatment varied over the study period. Seven children received a bone marrow allograft from a full match family donor and three a matched unrelated donor transplant after failed treatment with antilymphocyte globulin. The remainder were treated with antilymphocyte globulin (n = 11), antilymphocyte globulin and oxymetholone (n = 4), oxymetholone with or without prednisolone (n = 12), or supportive treatment alone (n = 1). With a minimum follow up of one year since treatment, the five year survival was 70% for bone marrow transplantation with a family donor, 30% for antilymphocyte globulin, and 25% for oxymetholone. All three children with a matched unrelated donor transplant died. The prognosis of acquired aplastic anaemia remains poor for most children and new approaches to treatment are urgently required.

Two hundred and nine children presenting consecutively with acute lymphoblastic leukaemia to a regional paediatric oncology unit were investigated to determine the prognostic significance of various factors at diagnosis. There was a strong positive correlation between the pretreatment haemoglobin level and the percentage of bone marrow blast cells in S phase of the cell cycle as assessed by flow cytometry. Patients with T- and B-cell leukaemia had significantly higher haemoglobin levels than non-B non-T patients. In patients with total white cell counts less than 20 X 10(9)/l, aged less than 13 years, and no mediastinal mass, there was no association of haemoglobin with length of first remission. However, among those with white blood counts greater than 20 +/- 10(9)/l there was a strong positive trend towards shorter remission with higher haemoglobin levels. Children with high white blood counts at diagnosis and low haemoglobin levels may have a better prognosis than predicted by the white blood count alone.

We have assessed testicular function with luteinising hormone-releasing hormone (LH-RH) and human chorionic gonadotrophin stimulation tests in 44 boys previously treated with, or currently receiving, chemotherapy for acute lymphoblastic leukaemia (ALL). At the same time a testicular biopsy was performed in each boy and the morphology was studied. Histologically the chemotherapy appeared to damage the tubular system in particular, and the degree of damage was assessed by estimating the tubular fertility (TF) index which is defined as the percentage of seminiferous tubules containing identifiable spermatogonia. The mean TF index in all 44 biopsies was 51%. Only 2 of the 44 boys showed an absent or blunted testosterone response to human chorionic gonadotrophin. This suggests that Leydig cell function is rarely impaired by such chemotherapy and that most of the boys, similarly treat for ALL, will undergo normal pubertal maturation. Apart from the basal luteinising hormone (LH) levels in the prepubertal group which could not be compared, the median basal serum follicle-stimulating hormone (FSH), LH, and testosterone concentrations, the median peak FSH and LH responses to LH-RH, and the mean plasma testosterone responses to human chorionic gonadotrophin stimulation did not differ between the prepubertal, early pubertal, and late pubertal groups compared with normal boys of similar pubertal maturation. Three of 32 prepubertal ALL boys, and 5 of 12 pubertal ALL boys showed abnormalities of gonadotrophin secretion. The increased frequency of abnormalities of FSH secretion in the pubertal ALL boys compared with the prepubertal ALL boys could not be explained by more severe tubular damage in the former group. We conclude that moderately severe damage to the tubular system of the testis unassociated with Leydig cell impairment may not be detected in the prepubertal boy with current tests of testicular function.

A 5-year-old with adrenocortical carcinoma presented with acute paraplegia. The tumour was initially nonfunctioning but finally showed rapid dissemination and the patient then developed Cushingoid features and virilisation.

A simple method for treating supraventricular tachycardias is described--ice cubes are applied to the nose and upper lip. It should be particularly useful in younger children and depends on a sound physiological principle.

A 9 year old girl underwent laparotomy because of intermittent diarrhoea, present since infancy. Histology of a mass at the head of pancreas and multiple hepatic nodules suggested an apudoma. Plasma serotonin and urinary excretion of 5 hydroxy indole acetic acid were raised. The child is asymptomatic four years after diagnosis.

In the case of a boy with a relapsed thrombocytopenic purpura removal of a splenunculus, shown by radioisotope scanning, resulted in a partial remission. The significance of the association of relapse in ITP and the presence of splenunculi remains unknown: investigation of similar cases would clarify the matter.