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1.
Br J Haematol ; 149(5): 722-33, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20331462

ABSTRACT

Vincristine plus steroid pulses have long been a part of maintenance treatment in many protocols for childhood acute lymphoblastic leukaemia (ALL). A collaborative individual patient data meta-analysis of all randomised trials of the addition of vincristine plus prednisone/prednisolone (VP) pulses in childhood ALL was updated and extended to include trials comparing vincristine plus dexamethasone (VD) pulses to maintenance without pulses. VP pulses improved event-free survival (EFS) (70.1% vs. 62.0% at 5 years; odds ratio (OR) = 0.71; 95% confidence interval (CI) = 0.61-0.84; P = 0.00004); VD pulses did not have a significant effect (80.9% vs. 79.9% 5 year EFS; OR = 0.94; 95% CI = 0.80-1.11; P = 0.5). Heterogeneity between groups (VP or VD) was significant (P = 0.02). Neither treatment clearly affected overall survival. The difference between the VP and VD results is probably due to the greater early intensity of the backbone of the VD trial protocols and improved outcome seen in the VD trials, which were more recent. Pulses may still be useful in cases where less intensive early therapy is used and the balance between these treatments in terms of both effectiveness and toxicity needs to be considered.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Child , Child, Preschool , Female , Glucocorticoids/administration & dosage , Humans , Infant , Infant, Newborn , Male , Randomized Controlled Trials as Topic , Survival Analysis , Treatment Outcome , Vincristine/administration & dosage , Young Adult
2.
Leukemia ; 24(2): 450-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20016529

ABSTRACT

Despite the success of contemporary treatment protocols in childhood acute lymphoblastic leukaemia (ALL), relapse within the central nervous system (CNS) remains a challenge. To better understand this phenomenon, we have analysed the changes in incidence and pattern of CNS relapses in 5564 children enrolled in four successive Medical Research Council-ALL trials between 1985 and 2001. Changes in the incidence and pattern of CNS relapses were examined and the relationship with patient characteristics was assessed. The factors affecting outcome after relapse were determined. Overall, relapses declined by 49%. Decreases occurred primarily in non-CNS and combined relapses with a progressive shift towards later (> or =30 months from diagnosis) relapses (P<0.0001). Although isolated CNS relapses declined, the proportional incidence and timing of relapse remained unchanged. Age and presenting white blood cell (WBC) count were risk factors for CNS relapse. On multivariate analysis, the time to relapse and the trial period influenced outcomes after relapse. Relapse trends differed within biological subtypes. In ETV6-RUNX1 ALL, relapse patterns mirrored overall trends whereas in high hyperdiploidy (HH) ALL, these seem to have plateaued over the latter two trial periods. Intensive systemic and intrathecal chemotherapy have decreased the overall CNS relapse rates and changed the patterns of recurrence. The heterogeneity of therapeutic response in the biological subtypes suggests room for further optimization using currently available chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/epidemiology , Neoplasm Recurrence, Local/epidemiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Brain Neoplasms/therapy , Child , Child, Preschool , Combined Modality Therapy , Cranial Irradiation , Female , Follow-Up Studies , Humans , Immunophenotyping , Incidence , Infant , Leukocyte Count , Male , Neoplasm Recurrence, Local/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Remission Induction , Risk Factors , Stem Cell Transplantation , Survival Rate , Treatment Outcome , United Kingdom
3.
Br J Cancer ; 101(11): 1939-45, 2009 Dec 01.
Article in English | MEDLINE | ID: mdl-19888224

ABSTRACT

BACKGROUND: Between 1979 and 2001, an analysis of cancer survival in young people in England, aged 13 to 24 years, showed overall improvements. However, for some diagnostic groups, little or no increases were observed. The aim of this study was to analyse the regional distribution of cancer survival in teenagers and young adults in England in order to identify patterns and potential for improvements at a regional scale. METHODS: We examined geographical and temporal patterns in relative survival in cancer patients aged 13-24 years in England during the time period 1979-2001. Cancer cases were grouped according to an internationally recognised morphology-based diagnostic scheme. RESULTS: For most diagnostic groups, there was little variation in survival between regions, except for testicular germ cell tumours (P=0.006) and colorectal carcinoma (P=0.002). For certain diagnostic groups, the temporal pattern in survival differed between regions. However, in regions that showed poor survival during the early part of the study period, greatest improvements were observed in groups such as acute lymphoid leukaemia, acute myeloid leukaemia, testicular tumours and melanoma. CONCLUSION: In conclusion, there was a reduction in the differences in survival between regions during the study period.


Subject(s)
Neoplasms/mortality , Adolescent , Adult , England/epidemiology , Humans , Population Dynamics , Survival Rate , Young Adult
4.
Indian J Cancer ; 46(4): 264-73, 2009.
Article in English | MEDLINE | ID: mdl-19749456

ABSTRACT

There has been enormous progress in the treatment of childhood cancer in the developed world and the epidemiology in these countries is well described. Hitherto, there has been no attempt to systematically study the burden of childhood cancer in India or to understand how the occurrence and outcome of the disease varies across the country. We have reviewed the epidemiology (incidence, survival, and mortality) of childhood cancer across different population-based cancer registries in India and also compared it with data from the resource-rich countries. Incidence and mortality data were obtained from the National Cancer Registry Program Reports and the Cancer Incidence in 5 Continents publications. Further, a comprehensive review of medical literature was done for information on individual cancers as well as survival data. 1.6 to 4.8% of all cancer in India is seen in children below 15 years of age and the overall incidence of 38 to 124 per million children, per year, is lower than that in the developed world. The considerable inter-regional variation in incidence and mortality rates across India suggests a possible deficiency in ascertainment of cases and death notification, particularly in rural areas. The marked male preponderance of Hodgkin's disease, lower incidence of central nervous system tumors, and higher incidence of retinoblastoma merit further analysis.


Subject(s)
Neoplasms/epidemiology , Adolescent , Age Distribution , Child , Child, Preschool , Female , Humans , Incidence , India , Infant , Infant, Newborn , Male , Registries
5.
Br J Cancer ; 100(1): 188-93, 2009 Jan 13.
Article in English | MEDLINE | ID: mdl-19127271

ABSTRACT

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0-14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981-2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27-2.99) for osteosarcoma, 1.90 (1.58-2.21) for Ewing sarcoma and 0.21 (0.11-0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6-5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981-2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91-0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98-1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered.


Subject(s)
Bone Neoplasms/epidemiology , Adolescent , Bone Neoplasms/mortality , Child , Child, Preschool , England/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Osteosarcoma/epidemiology , Proportional Hazards Models , Sarcoma, Ewing/epidemiology , Survival Rate
6.
Br J Cancer ; 99(5): 830-5, 2008 Sep 02.
Article in English | MEDLINE | ID: mdl-18728673

ABSTRACT

Cancer is the leading cause of disease-related death in teenagers and young adults aged 13-24 years (TYAs) in England. We have analysed national 5-year relative survival among more than 30,000 incident cancer cases in TYAs. For cancer overall, 5-year survival improved from 63% in 1979-84 to 74% during 1996-2001 (P<0.001). However, there were no sustained improvements in survival over time among high-grade brain tumours and bone and soft tissue sarcomas. Survival patterns varied by age group (13-16, 17-20, 21-24 years), sex and diagnosis. Survival from leukaemia and brain tumours was better in the youngest age group but in the oldest from germ-cell tumours (GCTs). For lymphomas, bone and soft tissue sarcomas, melanoma and carcinomas, survival was not significantly associated with age. Females had a better survival than males except for GCTs. Most groups showed no association between survival and socioeconomic deprivation, but for leukaemias, head and neck carcinoma and colorectal carcinoma, survival was significantly poorer with increasing deprivation. These results will aid the development of national specialised service provision for this age group and identify areas of clinical need that present the greatest challenges.


Subject(s)
Neoplasms/pathology , Survival Analysis , Adolescent , Adult , England , Humans , Neoplasms/classification , Socioeconomic Factors
7.
Br J Cancer ; 99(1): 219-23, 2008 Jul 08.
Article in English | MEDLINE | ID: mdl-18594545

ABSTRACT

Survival from childhood leukaemia has increased, but the proportion of children cured is unknown. The proportion 'cured' is defined as the proportion of survivors for whom, as a group, there is no longer excess mortality compared to the general population. Average time to cure is defined as the time since diagnosis at which the excess mortality rate has declined to or below a predetermined small value. Data on children diagnosed with leukaemia during 1971-2000 in Great Britain were used to estimate trends in survival, the proportion cured and the average time to cure. Five-year survival for all types of leukaemia combined rose from 33 to 79% by 2000. The percentage cured rose from 25 to 68% by 1995; it is predicted to increase to 73% for those diagnosed more recently. Average time to cure increased from 12 years (95% confidence interval (CI): 11-14) to 19 years (95% CI: 14-26) for lymphoid leukaemia (average annual increase of 0.3 years; P<0.001), but remained at about 5 years for acute nonlymphoblastic leukaemia. The proportion of children cured of leukaemia has risen dramatically, but the period of excess mortality associated with lymphoid leukaemia has also increased, possibly because of late relapse, secondary malignancy and toxicity from treatment.


Subject(s)
Leukemia/mortality , Leukemia/therapy , Registries , Child , Humans , Time Factors , United Kingdom/epidemiology
8.
Br J Cancer ; 98(6): 1125-31, 2008 Mar 25.
Article in English | MEDLINE | ID: mdl-18334973

ABSTRACT

Childhood B-cell precursor (BCP) ALL is thought to be caused by a delayed immune response to an unidentified postnatal infection. An association between BCP ALL and HLA class II (DR, DQ, DP) alleles could provide further clues to the identity of the infection, since HLA molecules exhibit allotype-restricted binding of infection-derived antigenic peptides. We clustered >30 HLA-DPB1 alleles into six predicted peptide-binding supertypes (DP1, 2, 3, 4, 6, and 8), based on amino acid di-morphisms at positions 11 (G/L), 69 (E/K), and 84 (G/D) of the DPbeta(1) domain. We found that the DPbeta11-69-84 supertype GEG (DP2), was 70% more frequent in BCP ALL (n=687; P<10(-4)), and 98% more frequent in cases diagnosed between 3 and 6 years (P<10(-4)), but not <3 or >6 years, than in controls. Only one of 21 possible DPB1 supergenotypes, GEG/GKG (DP2/DP4) was significantly more frequent in BCP ALL (P=0.00004) than controls. These results suggest that susceptibility to BCP ALL is associated with the DP2 supertype, which is predicted to bind peptides with positively charged, nonpolar aromatic residues at the P4 position, and hydrophobic residues at the P1 and P6 positions. Studies of peptide binding by DP2 alleles could help to identify infection(s) carrying these peptides.


Subject(s)
Genetic Predisposition to Disease , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Case-Control Studies , Child , Child, Preschool , Female , Gene Frequency , Genotype , HLA-DP Antigens , HLA-DP beta-Chains , Humans , Infant, Newborn , Male
9.
Br J Cancer ; 97(11): 1588-94, 2007 Dec 03.
Article in English | MEDLINE | ID: mdl-17987032

ABSTRACT

We examined cancer mortality at ages 13-29 years in England and Wales between 1981 and 2005, a total of 20 026 deaths over approximately 303 million person-years (mpy) at risk by sex, age group and time period. Overall, the mortality rate was 65.6 per mpy. Malignant neoplasms of the central nervous system showed the highest rate (8.5), followed by myeloid and monocytic leukaemia (6.6), lymphoid leukaemia (6.4), malignant bone tumours (5.4) and non-Hodgkin's lymphoma (5.2). These groups together accounted for almost 50% of all cancer deaths. The mortality rate for males (72.4) was 23% higher than for females (58.6) (P-value <0.0001). Males showed significantly higher mortality rates than females in almost all diagnostic groups, in general, mortality increasing with age (P-value <0.0001). There were significant decreases in mortality over time, the annual percentage change between 1981 and 2005 being minus 1.86 (95% confidence interval -2.09 to -1.62). Cancer groups with the highest mortality differed from those with the highest incidence.


Subject(s)
Mortality/trends , Neoplasms/mortality , Adolescent , Adult , England/epidemiology , Female , Humans , Male , Registries/statistics & numerical data , Wales/epidemiology
10.
Br J Cancer ; 96(11): 1760-6, 2007 Jun 04.
Article in English | MEDLINE | ID: mdl-17505509

ABSTRACT

Data on 35,291 individuals with cancer, aged 13-24 years, in England from 1979 to 2001 were analysed by region and socio-economic deprivation of census ward of residence, as measured by the Townsend deprivation index. The incidence of leukaemia, lymphoma, central nervous system tumours, soft tissue sarcomas, gonadal germ cell tumours, melanoma and carcinomas varied by region (P<0.01, all groups) but bone tumour incidence did not. Lymphomas, central nervous system tumours and gonadal germ cell tumours all had higher incidence in less deprived census wards (P<0.01), while chronic myeloid leukaemia and carcinoma of the cervix had higher incidence in more deprived wards (P<0.01). In the least deprived wards, melanoma incidence was nearly twice that in the most deprived, but this trend varied between regions (P<0.001). These cancer incidence patterns differ from those seen in both children and older adults and have implications for aetiology and prevention.


Subject(s)
Geography , Neoplasms/epidemiology , Neoplasms/etiology , Psychosocial Deprivation , Adolescent , Adult , Bone Neoplasms/epidemiology , Brain Neoplasms/epidemiology , Carcinoma/epidemiology , England/epidemiology , Female , Humans , Incidence , Leukemia/epidemiology , Lymphoma/epidemiology , Male , Melanoma/epidemiology , Neoplasms, Germ Cell and Embryonal/epidemiology , Sarcoma/epidemiology , Socioeconomic Factors
11.
Br J Cancer ; 96(8): 1265-71, 2007 Apr 23.
Article in English | MEDLINE | ID: mdl-17387343

ABSTRACT

Gardner and co-workers advanced the hypothesis that the Seascale leukaemia cluster could have been caused by new mutations in germ cells, induced by paternal preconceptional irradiation (PPI) exposure at the Sellafield nuclear installation. Since evidence has shown that PPI can increase the de novo germline mutation rate in hypervariable minisatellite loci, we investigated the hypothesis that sporadic childhood leukaemia might be associated with an increased parental germline minisatellite mutation rate. To test this hypothesis, we compared de novo germline mutation rates in the hypervariable minisatellite locus, CEB1, in family trios (both parents and their child) of children with leukaemia (n=135) compared with unaffected control families (n=124). The majority of case and control germline mutations were paternal (94%); the mean paternal germline mutation rates of children with leukaemia (0.083) and control children (0.156) were not significantly different (odds ratio, 95% confidence interval: 0.50, 0.23-1.08; P=0.11). There were no significant differences in case and control parental allele sizes, case and control germline mutation progenitor allele sizes (2.74 vs 2.54 kb; P=0.56), case and control mutant allele sizes (2.71 vs 2.67 kb; P=0.90), mutant allele size changes (0.13 vs 0.26 kb; P=0.10), or mutational spectra. Within the limitation of the number of families available for study, we conclude that childhood leukaemia is unlikely to be associated with increased germline minisatellite instability.


Subject(s)
Germ-Line Mutation , Intracellular Signaling Peptides and Proteins/genetics , Leukemia/genetics , Minisatellite Repeats , Parents , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Male
12.
Pediatr Blood Cancer ; 48(5): 555-60, 2007 May.
Article in English | MEDLINE | ID: mdl-16652350

ABSTRACT

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of pathological Langerhans cells, for which the aetiology and pathogenesis remain largely unknown. PROCEDURE: Information on the 101 children with LCH registered with the population-based Manchester Children's Tumour Registry (MCTR) between 1954 and 1998 was extracted from the records of the MCTR. This included age, sex, date of diagnosis, systems affected at diagnosis and follow-up. RESULTS: The overall incidence rate for LCH was 2.6 cases per million child years. In those under 1 year of age the incidence rate was 9.0 cases per million child years, compared to 0.7 cases per million in those aged 10-14 years (P < 0.0001 for age trend). There was no evidence of seasonal variation in presentation by month of birth or first symptom. Bone was the most common site of disease involvement (67% of cases), followed by skin (37%) and soft tissue (22%). The overall survival rate has improved over time, from 57% in 1954-1968 to 74% in 1985-1998. Ninety percent of deaths were due to disease progression, the remainder were due to complications of intensive therapy. The site of LCH lesions and extent of disease present at diagnosis strongly predicted survival outcome. Patients with initial liver involvement had a 5-year survival rate of 25% compared with 93% for those with bone lesions alone at diagnosis. CONCLUSIONS: Incidence rates varied significantly by age at diagnosis, and have been stable over time. Survival has improved considerably over time, but varies strongly by age and systems affected at diagnosis.


Subject(s)
Histiocytosis, Langerhans-Cell/epidemiology , Adolescent , Age Factors , Bone and Bones/pathology , Child , Child, Preschool , Disease Progression , England/epidemiology , Female , Histiocytosis, Langerhans-Cell/mortality , Histiocytosis, Langerhans-Cell/pathology , Humans , Infant , Liver/pathology , Male , Seasons , Skin/pathology , Survival Rate
13.
Lancet ; 368(9544): 1339-48, 2006 Oct 14.
Article in English | MEDLINE | ID: mdl-17046466

ABSTRACT

BACKGROUND: 6-mercaptopurine has been a standard component of long-term continuing treatment for childhood lymphoblastic leukaemia, whereas 6-thioguanine has been mainly used for intensification courses. Since preliminary data have shown that 6-thioguanine is more effective than 6-mercaptopurine, we compared the efficacy and toxicity of the two drugs for childhood lymphoblastic leukaemia. METHODS: Consecutive children with lymphoblastic leukaemia diagnosed in the UK and Ireland between April, 1997, and June, 2002, were randomly assigned either 6-thioguanine (750 patients) or 6-mercaptopurine (748 patients) during interim maintenance and continuing therapy. All patients received 6-thioguanine during intensification courses. We analysed event-free and overall survival on an intention-to-treat basis. We obtained toxicity data using an adverse-event reporting system, with follow-up questionnaires to seek detailed information for specific toxicities. This trial is registered with the International Standard Randomised Controlled Number 26727615 with the name ALL97. FINDINGS: After a median follow up of 6 years, there was no difference in event-free or overall survival between the two treatment groups. Although 6-thioguanine conferred a significantly lower risk of isolated CNS relapse than did 6-mercaptopurine (odds ratio [OR] 0.53, 95% CI 0.30-0.92, p=0.02), the benefit was offset by an increased risk of death in remission (2.22, 1.20-4.14, p=0.01), mainly due to infections during continuing therapy. Additionally, 95 patients developed veno-occlusive disease of the liver. Of these, 82 were randomly assigned 6-thioguanine, representing 11% of all 6-thioguanine recipients. On long-term follow-up, about 5% of 6-thioguanine recipients have evidence of non-cirrhotic portal hypertension due to periportal liver fibrosis or nodular regenerative hyperplasia. INTERPRETATION: Compared with 6-mercaptopurine, 6-thioguanine causes excess toxicity without an overall benefit. 6-mercaptopurine should remain the thiopurine of choice for continuing therapy of childhood lymphoblastic leukaemia.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Mercaptopurine/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Thioguanine/therapeutic use , Adolescent , Antimetabolites, Antineoplastic/adverse effects , Child , Child, Preschool , Disease-Free Survival , Female , Follow-Up Studies , Humans , Infant , Male , Mercaptopurine/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Thioguanine/adverse effects
14.
Br J Haematol ; 129(6): 734-45, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15952999

ABSTRACT

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/m(2) 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.


Subject(s)
Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prednisolone/therapeutic use , Adolescent , Age Factors , Central Nervous System/pathology , Child , Child, Preschool , Dexamethasone/adverse effects , Disease-Free Survival , Female , Glucocorticoids/adverse effects , Humans , Infant , Leukemic Infiltration/prevention & control , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prednisolone/adverse effects , Recurrence , Treatment Outcome
15.
BMJ ; 330(7503): 1294, 2005 Jun 04.
Article in English | MEDLINE | ID: mdl-15849205

ABSTRACT

OBJECTIVE: To test the hypothesis that reduced exposure to common infections in the first year of life increases the risk of developing acute lymphoblastic leukaemia. Design and setting The United Kingdom childhood cancer study (UKCCS) is a large population based case-control study of childhood cancer across 10 regions of the UK. PARTICIPANTS: 6305 children (aged 2-14 years) without cancer; 3140 children with cancer (diagnosed 1991-6), of whom 1286 had acute lymphoblastic leukaemia (ALL). MAIN OUTCOME MEASURE: Day care and social activity during the first year of life were used as proxies for potential exposure to infection in infancy. RESULTS: Increasing levels of social activity were associated with consistent reductions in risk of ALL; a dose-response trend was seen. When children whose mothers reported no regular activity outside the family were used as the reference group, odds ratios for increasing levels of activity were 0.73 (95% confidence interval 0.62 to 0.87) for any social activity, 0.62 (0.51 to 0.75) for regular day care outside the home, and 0.48 (0.37 to 0.62) for formal day care (attendance at facility with at least four children at least twice a week) (P value for trend < 0.001). Although not as striking, results for non-ALL malignancies showed a similar pattern (P value for trend < 0.001). When children with non-ALL malignancies were taken as the reference group, a significant protective effect for ALL was seen only for formal day care (odds ratio = 0.69, 0.51 to 0.93; P = 0.02). Similar results were obtained for B cell precursor common ALL and other subgroups, as well as for cases diagnosed above and below age 5 years. CONCLUSION: These results support the hypothesis that reduced exposure to infection in the first few months of life increases the risk of developing acute lymphoblastic leukaemia.


Subject(s)
Child Day Care Centers/statistics & numerical data , Communicable Diseases/epidemiology , Environmental Exposure/statistics & numerical data , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Adolescent , Case-Control Studies , Child , Child, Preschool , Environmental Exposure/adverse effects , Humans , Infant , Odds Ratio , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Regression Analysis , Risk Factors , Social Behavior , United Kingdom/epidemiology
16.
Eur J Cancer ; 41(5): 741-8, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15763651

ABSTRACT

Within the context of a national population-based case-control study--the United Kingdom Childhood Cancer Study (UKCCS)--we aimed to explore relationships between perinatal and maternal factors and childhood hepatic tumours, for participants with data available from medical records. 26/28 children with hepatic tumours (22/24 hepatoblastomas, 4/4 hepatocellular carcinomas (HCC)) and 4753 age- and sex-matched controls were included. Polyhydramnios was associated with 0.9% of control pregnancies and 13.6% of case pregnancies (Odds Ratio (OR)=28.64, 95% Confidence Interval (CI)=6.94-118.21, P<0.0001); eclampsia or severe pre-eclampsia complicated the pregnancies of 16.7% of mothers whose children developed hepatoblastoma compared with 0.5% of control pregnancies (OR=52.50, 95% CI=10.75-257.05, P<0.0001). Three children with hepatoblastoma weighed <1500 g at birth, two of whom weighed <1000 g (OR for birthweight <1500 g=69.00, 95% CI=11.98-397.17, P<0.0001). Of children with hepatoblastoma, 50% (11/22) had records of congenital anomalies, as did two of their mothers. Three mothers of children with hepatoblastoma had diagnoses of cancer--two of papillary carcinoma of the thyroid and one of acute lymphoblastic leukaemia (ALL). Paediatricians and others should be alert to the possibility of familial or genetic syndromes in children with hepatoblastomas. Potential links between maternal pre-eclampsia, low birthweight and subsequent malignancy merit further investigation. Hepatoblastoma is an extremely rare childhood tumour, but understanding the mechanism(s) underlying severe pre-eclampsia and eclampsia may also shed light on factors that contribute to the development of hepatoblastoma.


Subject(s)
Carcinoma, Hepatocellular/etiology , Hepatoblastoma/etiology , Liver Neoplasms/etiology , Pregnancy Complications , Case-Control Studies , Child , Child, Preschool , Confidence Intervals , Female , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Male , Odds Ratio , Pregnancy
17.
Eur J Cancer ; 41(5): 749-59, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15763652

ABSTRACT

The United Kingdom Childhood Cancer Study was designed to examine the potential aetiological role of a range of perinatal and reproductive factors. Our use of clinical records permitted a more exact characterisation of reproductive events than is possible in investigations that rely on self-reporting; and the increased specificity with which antecedent events were measured produced more precise risk estimates, albeit ones based on progressively smaller numbers. Information on the conduct of this component of the study and results for 1485 children with haematological malignancies and 4864 controls are presented. The 'find' rate for obstetric records was high at 86% for cases, with 81% having information on both matched controls. Associations were seen for severe hyperemesis (Odds Ratio=3.6, 95%Confidence Interval=1.3-10.1, for all leukaemias), polyhydramnios (OR=4.0, 95%CI=1.5-10.3, for acute myeloid leukaemia (AML)), anaemia (haemoglobin <10 g, OR=2.6, 95%CI=1.7-4.1, for AML), and pre-eclampsia (OR=1.7, 95%CI=1.1-2.7, for non-Hodgkin's lymphoma). Babies who developed leukaemia were heavier at birth (>4000 g, OR=1.2, 95%CI=1.0-1.4), as were their older siblings (>4000 g, OR=1.4, 95%1.0-1.9). Mothers' whose children developed common B-cell precursor acute lymphoblastic leukaemia (ALL) were more likely to have had a previous molar pregnancy (OR=5.2, 95%CI=1.9-14.7). Gender-specific analysis revealed that findings often differed markedly for boys and girls; and, in common with other reports, strong associations with Down's syndrome were seen for both ALL and AML.


Subject(s)
Hematologic Neoplasms/etiology , Pregnancy Complications , Acute Disease , Adolescent , Birth Weight , Case-Control Studies , Child , Child, Preschool , Down Syndrome , Female , Humans , Infant , Infant, Newborn , Leukemia, Myeloid/etiology , Male , Odds Ratio , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Pregnancy
18.
Eur J Cancer ; 40(15): 2280-6, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15454254

ABSTRACT

Symptom interval (SI), the time from first symptom/sign to diagnosis and initiation of treatment, appears to be principally influenced by tumour biology. Whether the age of the patient, patient delay, professional delay and access to health professionals influences the SI in bone tumours was investigated in this study. 115 patients with newly diagnosed osteosarcoma and Ewing's sarcoma were retrospectively reviewed. The median total SI for all bone tumours was 3.8 months (range 1-46 months). Patients older than 12 years had a longer SI (P = 0.05) and more patient delays (P = 0.02). Total SI and professional delays were longer if the General Practitioner was first seen compared with an Accident and Emergency Consultant (P = 0.02 and 0.02, respectively). However, SI did not influence overall and event-free survival in this series. Bone tumour patients have long SIs that are significantly affected by age and local health-care support systems. Early referral to specialists would help to alleviate anxiety and distress to the patient and family, even if currently delay does not influence outcome.


Subject(s)
Bone Neoplasms , Osteosarcoma , Sarcoma, Ewing , Adolescent , Adult , Bone Neoplasms/diagnosis , Bone Neoplasms/therapy , Child , Child, Preschool , Early Diagnosis , Family Practice/statistics & numerical data , Female , Humans , Male , Osteosarcoma/diagnosis , Osteosarcoma/secondary , Osteosarcoma/therapy , Patient Acceptance of Health Care/statistics & numerical data , Referral and Consultation/statistics & numerical data , Retrospective Studies , Sarcoma, Ewing/diagnosis , Sarcoma, Ewing/secondary , Sarcoma, Ewing/therapy , Survival Analysis , Time Factors
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