Cross-reactivity to porcine factor VIII of factor VIII inhibitors in patients with haemophilia in Australia and New Zealand.

BACKGROUND: Inhibitory antibodies which neutralise factor VIII develop in 10-20% of individuals with inherited haemophilia A and rarely as autoantibodies in normal individuals to cause acquired haemophilia. The antibodies are directed against human factor VIII but cross-react to varying degrees with porcine factor VIII. Porcine factor VIII can be used for treatment in individuals with low cross-reactivity. AIMS: To determine the cross-reactivity of factor VIII inhibitors between human factor VIII and porcine factor VIII, in a population of patients with inherited and acquired haemophilia A. Also, to determine whether patients with inherited haemophilia and inhibitors have a higher incidence of factor VIII gene inversion in intron 22. METHODS: Samples and data sheets from 43 patients with inherited and ten with acquired haemophilia were submitted from hospitals in Australia and New Zealand. Inhibitor levels to human and porcine factor VIII were measured by the Bethesda method in 39 with inherited and nine with acquired haemophilia A. RESULTS: Of 39 patients with inherited haemophilia A, cross-reactivity was 0% in 17 patients, 1-19% in six, 20-39% in 11 and 40-80% in five. In six of nine patients with acquired haemophilia cross-reactivity was < or = 7%. In inherited severe haemophilia A, the frequency of the intron 22 inversion was not greater in 37 study patients than in 28 patients without an inhibitor. CONCLUSIONS: Many patients in Australia and New Zealand with inhibitors to human factor VIII presently show a low or absent level of cross-reactivity to porcine factor VIII. These may respond to treatment with this concentrate at least in the short term. There remains a group of patients with high cross-reactivity who will respond only to recombinant factor VIIa or prothrombin complex concentrates.

Childhood cancer incidence in Australia, 1982-1991.

The data of the Australian Paediatric Cancer Registry on childhood cancer incidence in Australia for the 10-year period 1982-1991 are presented. The crude average annual incidence of cancer in children under the age of 15 years was 13.8 per 100,000. The incidence of childhood cancer in Australia is rising. Significant increases were seen in acute non-lymphoblastic leukaemia, astrocytoma and melanoma. The age-standardised incidence of 14.4 per 100,000 is about 34% higher than in the UK. Most types of cancer had a higher incidence in Australia than in the UK, and the difference was significant for acute lymphoblastic leukaemia, astrocytoma and melanoma. Of particular interest is malignant melanoma, whose incidence in Australia is more than 5 times that in the UK, as a result of excessive UV exposure. Australia has a higher incidence of Ewing's tumour than osteosarcoma, nearly twice that of the UK. International comparative studies may help to elucidate the aetiology of these tumours.

Childhood melanoma in Australia.

Data from a population-based registry, the Australian Paediatric Cancer Registry, were used to determine the incidence of malignant melanoma in children under 15 years of age in Australia. Over a 17-year period, 217 cases were identified. For the period 1977-89 inclusive, the annual age incidence was 0.34 per 100,000. There was some variation in incidence between the different states with Queensland recording the highest incidence at 0.97 per 100,000, the highest reported incidence in the world for childhood melanoma. Most of the cases occurred in children aged 13 or 14 years old with girls affected slightly more often, the sex ratio being 0.92. There was a statistically significant seasonal variation with fewer cases being diagnosed during the winter months. The commonest site was the trunk. Two of the cases were second neoplasms. This series demonstrates the need for increased education of children living in tropical and subtropical regions about the dangers of sun exposure and of methods of reducing exposure. Children who have undergone chemotherapy appear to be at particular risk.

Incidence trends in childhood cancer in Queensland, 1973-1988.

OBJECTIVE: To determine whether there are any secular trends in the incidence of childhood cancer in Queensland. DESIGN: A retrospective epidemiological study of the incidence of cancer in children, aged 0-12 years, in Queensland during the 16-year period 1973-1988 inclusive. SETTING: Cases were found from the records of the Queensland Childhood Malignancy Registry. Ascertainment is believed to be virtually complete for children aged 0-12 years. PARTICIPANTS: All children who were resident in Queensland and less than 13 years of age at the time of diagnosis of cancer. The cases included all malignant neoplasms and also all intracranial neoplasms in children but excluded Langerhans' cell histiocytosis. MAIN OUTCOME MEASUREMENTS: The incidence by year of diagnosis was calculated for each of a number of standard diagnostic groups of neoplasms. These data were analysed by the chi 2, for trend test. RESULTS: Cancer incidence was found to be increasing at a rate of about 0.9% per year. The rise was almost entirely accounted for by a rise in incidence among boys, whereas there was virtually no change in the incidence in girls. Statistically significant increases in incidence were found in acute non-lymphocytic leukaemia and also in non-Hodgkin's lymphoma in boys; Hodgkin's disease was found to be decreasing in incidence. CONCLUSIONS: The results of this study emphasise the importance of childhood cancer incidence surveillance in Australia to determine whether these trends will continue in the future. The findings also indicate a need for continuing research in childhood cancer epidemiology.

Childhood cancer incidence in Queensland, 1979-88.

Data on the incidence of childhood cancer in Queensland during the 10-year period 1979-88 are presented. During this period, 786 cases were registered. The average annual crude and age-standardized (to the world population) incidence rates for both sexes were 12.63 and 13.30 per 100,000 respectively. The incidence of cancer in males is unusually high, as is the sex ratio of 1.57. ALL accounted for 78% of all leukaemias. There appears to have been a decline in the incidence of Hodgkin's disease, especially in older children, compared with an earlier Queensland series. Ewing's tumour remains commoner than osteosarcoma. Some modifications to the classification scheme for childhood cancer are proposed. The most important of these is the omission of Langerhans-cell histiocytosis, which is not now regarded as a neoplasm.

Carcinomas in childhood. A registry-based study of incidence and survival.

During a 10 year period, 1971-80, there were 234 children in Great Britain younger than 15 years with a diagnosis of carcinoma registered in Great Britain. These cases represented approximately 2% of all childhood malignant disease. The most common primary site was the thyroid, followed by the nasopharynx and the adrenal cortex. With the exception of adrenocortical tumors, most of the carcinomas occurred in children older than 10 years. In some patients there was a genetic predisposition to neoplasia. Children with carcinomas of the thyroid and female genital tract have an excellent prognosis with 5-year survival rates of over 90%. The prognosis for other sites was generally less favorable; 60% of children with nasopharyngeal tumors were alive at 5 years from diagnosis but less than 20% of those with carcinomas of the gastrointestinal tract or the adrenal cortex.

What causes childhood leukaemia? Some beliefs of parents of affected children.

The theories of parents about the cause of their children's leukaemia have been documented in the course of a case-control study. From a sample of 175 children who were diagnosed as having acute lymphoblastic leukaemia, 91.4% of their parents put forward their theories. Some of these theories were related clearly to material that had been published and therefore had some scientific validity. Other theories often had no apparent scientific basis. Persons who are involved in the care of children with leukaemia should be aware of the wide variety of theories that are held by their parents so that they may provide counselling which could be of help in the relief of feelings of anxiety or guilt among the parents. Parents should always be afforded the opportunity to put forward their own theories so that they may be discussed on a rational basis. It is conceivable that some parents might put forward new hypotheses about leukaemogenesis that could be tested scientifically.

Cerebral astrocytoma as a complication of acute lymphoblastic leukaemia.

A boy who developed acute lymphoblastic leukaemia at the age of two years and 10 months had several central nervous system relapses, and received two courses of cranial irradiation, each of 24 Gy, in addition to systemic and intrathecal chemotherapy. Nearly 10 years after the onset of his leukaemia he developed a brain stem astrocytoma from which he died. This appears to be a rare occurrence, and the role of the treatment in the induction of his second tumour is discussed. The need for the long-term follow-up of cancer patients after apparent cure is emphasized.

Childhood cancer survival trends in Queensland 1956-80.

The true survival rates for the various forms of childhood cancer are best determined from a population-based study rather than from the results of clinical trials. Population-based survival rates have been calculated for four periods between 1956 and 1980 in Queensland. There was a significant improvement in survival for children who developed cancer after 1973 compared with those diagnosed before this date. There has however been no significant improvement in the survival rate for childhood cancer overall, or for acute lymphoblastic leukaemia since 1973. Over the 25 year period significant trends in survival rates were seen in acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin's disease, Wilms' tumour, medulloblastoma, and retinoblastoma. No such trend was seen for acute non-lymphoblastic leukaemia, neuroblastoma, rhabdomyosarcoma, juvenile or anaplastic astrocytoma, brain stem glioma, histiocytosis X, or bone tumours. There is a need for continuing research into better methods of treatment of childhood cancer.

Social class as a prognostic variable in acute lymphoblastic leukaemia.

We studied the relationship between social class and prognosis in children with acute lymphoblastic leukaemia. Seventy children who were commencing on curative therapy, and who received central nervous system prophylaxis, were included in the study. Children from social classes 1 to 5 had a significantly better five-year survival rate and duration of first remission than children from social classes 6 and 7. There was no apparent difference either in the treatment given to the two groups or in the clinical and haematological parameters studied. A study of the causes of this difference in survival could lead to better over-all results in the treatment of childhood leukaemia.

The relationship of incidence of childhood lymphoblastic leukaemia to social class.

A study has been made of the relationship between socio-economic factors and the incidence of acute lymphoblastic leukaemia (ALL) of childhood. It was found that the incidence of childhood ALL in 12 areas of Queensland. Australia, correlated well with some indicators of above-average socio-economic status for these areas. A similar result was found when Brisbane City was studied separately. Social class was determined from the fathers' occupations at the time of diagnosis. There was found to be a higher than expected number of ALL cases in each of the upper 5 social classes and a lower than expected number in the remaining 2 lower classes. Factors associated with differences in lifestyle amongst the various social classes may increase or decrease the risk of development of ALL.

Incidence of childhood tumours in Queensland.

The incidence of childhood cancer in Queensland has been studied using the data of the population-based Queensland Childhood Malignancy Registry. During the 7-year period 1973-1979, 454 cases were registered, giving an annual age-specific incidence of 11.34/10(5) for the age group 0-14 years inclusive. There was a male/female ratio of 1.36. The commonest group of diseases was that of the leukaemias, followed by that of CNS tumours. The incidences of the various types of tumour in Queensland have been compared with those from other reported series. The incidence of leukaemia was midway between that of U.S. whites and that of Manchester, while the incidences of lymphoma and Wilms' tumour were much closer to those of the United States. Ewing's tumour was considerably commoner than osteosarcoma.

Epidemiology of acute lymphoblastic leukaemia of childhood in Brisbane.

The incidence of acute lymphoblastic leukaemia of childhood in the Brisbane Statistical Division has been studied. Sixty-four cases occurred during a five-year period. A significant difference between the two subdivisions of the Statistical Division was found, with a higher incidence in Brisbane City than in the surrounding area. The average age at presentation of the leukaemic children within Brisbane City was significantly higher than in the rest of the Brisbane Statistical Division. Various socioeconomic and demographic differences exist between the two populations, and these may be responsible for the variation in leukaemia incidence. The findings indicate the need for further, more detailed, epidemiological studies.