Allergy and Risk of Childhood Leukaemia: Results from the UKCCS

We investigated the relationship between childhood leukaemia and preceding history of allergy. A nationwide case-control study of childhood cancers was conducted in the United Kingdom with population-based sampling of cases (n = 839) and controls (n = 1,337), matched on age, sex and region of residence. Information about clinically diagnosed allergies was obtained from primary care records. More than a third of subjects had at least one allergy diagnosed prior to leukaemia diagnosis (cases) or pseudo-diagnosis (controls). For both total acute lymphoblastic leukaemia (ALL) and common-ALL/precursor B-cell ALL (c-ALL), a history of eczema was associated with a 30% significant reduction in risk: the odds ratios (OR) and 95% confidence intervals (CI) were 0.70 (0.51-0.97) and 0.68 (0.48-0.98), respectively. Similar associations were observed for hayfever (OR = 0.47; 95% CI: 0.26-0.85 and OR = 0.62; 95% CI: 0.33-1.16 for ALL and c-ALL, respectively). No such patterns were seen either for asthma and ALL, or for any allergy and acute myeloid leukaemia. A comparative analysis of primary care records with parents recall of allergy revealed only moderate agreement with contemporaneous clinical diagnoses for both cases and controls - confirming the unreliability of parental report at interview. Our finding of a reciprocal relationship between allergy and ALL in children is compatible with the hypothesis that a dysregulated immune response is a critical determinant of childhood ALL

Cohort profile: the United Kingdom Childhood Cancer Study (UKCCS) – a UK- wide population- based study examining the health of cancer survivors

Purpose The United Kingdom Childhood Cancer Study’s (UKCCS’s) matched cohort was established to examine the longer term morbidity and mortality of individuals previously diagnosed with cancer before 15 years of age, comparing future healthcare patterns in 5-year cancer survivors to baseline activity seen in age- and sex-matched individuals from the general population.Participants Predicated on a national childhood cancer case-control study conducted in the early 1990s (4430 cases, 9753 controls) in England, Scotland and Wales, the case population comprises 3125 cancer survivors (>5 years), and the control population 7156 age- and sex-matched individuals from the general population who did not have cancer as a child. Participants are now being followed up via linkage to national administrative healthcare databases (deaths, cancers and secondary care hospital activity).Findings to date Enabling the creation of cohorts with minimal selection bias and loss to follow-up, the original case-control study registered all newly diagnosed cases of childhood cancer and their corresponding controls, regardless of their family’s participation. Early findings based on the registered case population found marked survival variations with age and sex across subtypes and differences with deprivation among acute lymphoblastic leukaemia (ALL) survivors. More recently, comparing the health-activity patterns of the case and control populations revealed that survivors of childhood ALL experienced excess outpatient and inpatient activity across their teenage/young adult years. Adding to increased risks of cancer and death and involving most clinical specialties, excesses were not related to routine follow-up monitoring and showed no signs of diminishing over time.Future plans With annual linkage updates, the UKCCS’s maturing population-based matched cohorts provide the foundation for tracking the health of individuals through their lifetime. Comparing the experience of childhood cancer survivors to that of unaffected general-population counterparts, this will include examining subsequent morbidity and mortality, secondary care hospital activity and the impact of deprivation on longer term outcomes

Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy

In severe congenital neutropenia (SCN), long-term therapy with granulocyte colony-stimulating factor (G-CSF) has reduced mortality from sepsis, revealing an underlying predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We have reported the early pattern of evolution to MDS/AML, but the long-term risk remains uncertain. We updated a prospective study of 374 SCN patients on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. Long-term, the annual risk of MDS/AML attained a plateau (2·3%/year after 10 years). This risk now appears similar to, rather than higher than, the risk of AML in Fanconi anaemia and dyskeratosis congenita.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79264/1/j.1365-2141.2010.08216.x.pd

Myeloid malignancies in the real-world : Occurrence, progression and survival in the UK’s population-based Haematological Malignancy Research Network 2004–15

Background: Population-based information on cancer incidence, prevalence and outcome are required to inform clinical practice and research; but contemporary data are lacking for many myeloid malignancy subtypes. Methods: Set within a socio-demographically representative UK population of ~4 million, myeloid malignancy data (N = 5231 diagnoses) are from an established patient cohort. Information on incidence, survival (relative & overall), transformation/progression, and prevalence is presented for >20 subtypes. Results: The median diagnostic age was 72.4 years (InterQuartile Range 61.6-80.2), but there was considerable subtype heterogeneity, particularly among the acute myeloid leukaemias (AML) where medians ranged from 20.3 (IQR 13.9-43.8) for AML 11q23 through to 73.7 (IQR 57.3-79.1) for AML with no recurrent genetic changes. Five-year Relative Survival (RS) estimates varied hugely; from 85% for indolent/treatable conditions like chronic myeloid leukaemia (89.8%, 95% CI 84.0-93.6). With a couple of notable exceptions, males experienced higher rates and worse survival than females: the age-standardized incidence rates of several conditions was 2-4 higher in males than females, and the 5-year RS for all subtypes combined was 48.8% (95% CI 46.5-51.2) and 60.4% (95% CI 57.7-62.9) for males and females respectively. During follow-up (potential minimum 2 years and maximum 11 years) myelodysplastic syndrome (MDS) progression to AML ranged from 25% for refractory anaemia with excess blasts through to 5% for refractory anaemia with ring sideroblasts: the median interval between MDS and AML diagnosis was 9.0 months (IQR 4.8-17.4 months). Conclusions: The marked incidence and outcome variations seen by subtype, sex and age, confirm the requirement for "real-world" longitudinal data to inform aetiological hypotheses, healthcare planning, and future monitoring of therapeutic change. Several challenges for routine cancer registration were identified, including the need to link more effectively to diagnostic and clinical data sources, and to review policies on the recording of progressions and transformations

Is bisexuality invisible? A review of sexualities scholarship 1970–2015

This article provides a review of sexualities scholarship within the social sciences between 1970 and 2015. It takes an innovative approach by focusing on the way in which bisexuality is addressed in this body of literature. The article reveals the marginalisation, under-representation and invisibility of bisexuality within and across the social sciences in relation to both bisexual experience and identity. Reasons for this varied across the different eras, including the heterosexist nature of the literature, the impact of gay and lesbian-focused identity politics, and queer deconstructionism. In addition, patterns of bisexual erasure and invisibility were uneven, with some scholarship taking inclusive approaches or criticising prejudice against bisexuality. The initial findings of the review were enriched by critical commentary from key relevant sociologists and political scientists. The article concludes that future sexualities scholarship could be enhanced by greater consideration of bisexuality

Population mixing for leukaemia, lymphoma and CNS tumours in teenagers and young adults in England, 1996-2005

Background: Little aetiological epidemiological research has been undertaken for major cancers occurring in teenagers and young adults (TYA). Population mixing, as a possible proxy for infectious exposure, has been well researched for childhood malignancies. We aimed to investigate effects of population mixing in this older age group using an English national cancer dataset.Methods: Cases of leukaemia, lymphoma and central nervous system (CNS) tumours amongst 15-24 year olds in England (diagnosed 1996-2005) were included in the study. Data were obtained by ward of diagnosis and linked to 1991 census variables including population mixing (Shannon index); data on person-weighted population density and deprivation (Townsend score) were also used and considered as explanatory variables. Associations between TYA cancer incidence and census variables were investigated using negative binomial regression, and results presented as incidence rate ratios (IRR) with 95% confidence intervals (CI).Results: A total of 6251 cases of leukaemia (21%), lymphoma (49%) and CNS tumours (30%) were analysed. Higher levels of population mixing were associated with a significant decrease in the incidence of CNS tumours (IRR = 0.83, 95% CI = 0.75-0.91), accounted for by astrocytomas and 'other CNS tumours'; however, there was no association with leukaemia or lymphoma. Incidence of CNS tumours and lymphoma was 3% lower in more deprived areas (IRR = 0.97, 95% CI = 0.96-0.99 and IRR = 0.97, 95% CI =0.96-0.98 respectively). Population density was not associated with the incidence of leukaemia, lymphoma or CNS tumours.Conclusions: Our results suggest a possible role for environmental risk factors with population correlates in the aetiology of CNS tumours amongst TYAs. Unlike studies of childhood cancer, associations between population mixing and the incidence of leukaemia and lymphoma were not observed

Systematic review and meta-analysis investigating the efficacy and safety of probiotics in people with cancer

Background/objectives: Probiotics are living microorganisms that confer a health benefit on the host when administered. This systematic review and meta-analysis investigates the efficacy and safety of probiotics in adult and paediatric patients diagnosed with cancer. Methods: A systematic review and meta-analysis was undertaken (PROSPERO registration: CRD42016050252). Randomised controlled trials (RCT), identified through screening multiple databases were included for analysis of efficacy. Non-randomised controlled trials and case reports were included for safety analysis. Outcomes included the reduction in the incidence and severity of diarrhoea, and adverse events. Where possible, data were combined for meta-analysis using a random-effects model. Planned subgroup analyses were not possible through marked heterogeneity of study characteristics. Results: Twenty one studies (N = 2982 participants) were included for assessment of efficacy. Probiotics may reduce the incidence of diarrhoea in patients with cancer [odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.34–0.78, 95% prediction interval (PI) 0.3–0.92, I-sq 36.9%, 5 studies] and the duration of pyrexia [standardised mean difference 0.39 days, 95% CI 0.35–0.43, I-sq 0.01%, 5 studies]. Twenty five studies (N = 2242) were included in the safety analysis. Five case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures. Definitions and reporting of adverse events were variable and inconsistent. Conclusions: There remain insufficient studies to assess the true effect of probiotics in people with cancer. Meta-analysis suggests probiotics may be beneficial but further studies are still required. Improved reporting of outcomes and adverse events in clinical trials are required to improve accuracy and confidence of conclusions drawn in future updates

Incidence of childhood acute lymphoblastic leukaemia in Yorkshire, UK

Between 1980 and 1998, in the north-west of England, a significant rise in childhood acute lymphoblastic leukaemia was caused by an increase in the precursor B-cell form of this disease. We analysed data on children who were diagnosed with leukaemia in Yorkshire, UK, between 1974 and 1997. The incidence of acute lymphoblastic leukaemia remained stable, although a non-significant yearly increase of 2·4% was noted for the precursor B-cell form of this disease from 1980 onwards. The precursor B-cell form accounted for 80% of all acute lymphoblastic leukaemia. Our data are not consistent with increasing incidence for precursor B-cell acute lymphoblastic leukaemia, although numbers of children with acute myeloid leukaemia are rising