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

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

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

Excess morbidity and mortality among survivors of childhood acute lymphoblastic leukaemia : 25 years of follow-up from the United Kingdom Childhood Cancer Study (UKCCS) population-based matched cohort

Objectives: To examine morbidity and mortality among teenagers and young adults (TYAs) previously diagnosed with acute lymphoblastic leukaemia (ALL) in childhood, and compare to the general TYA population. Design: National population-based sex-matched and age-matched case-control study converted into a matched cohort, with follow-up linkage to administrative healthcare databases. Setting: The study population comprised all children (0textendash14 years) registered for primary care with the National Health Service (NHS) in England 1992-1996. Participants: 1082 5-year survivors of ALL diagnosed <15 years of age (1992-1996) and 2018 unaffected individuals; followed up to 15 March 2020. Main outcome measures: Associations with hospital activity, cancer and mortality were assessed using incidence rate ratios (IRR) and differences. Results: Mortality in the 5-year ALL survivor cohort was 20 times higher than in the comparison cohort (rate ratio 21.3, 951.2 to 45.6), and cancer incidence 10 times higher (IRR 9.9 95.1 to 29.1). Hospital activity was increased for many clinical specialties, the strongest associations being for endocrinology; outpatient IRR 36.7, 957.3 to 93.4 and inpatient 19.7, 95.9 to 63.2 for males, and 11.0, 95.2 to 21.1 and 6.2 95.1 to 13.5, respectively, for females. Notable excesses were also evident for cardiology, neurology, ophthalmology, respiratory medicine and general medicine. Males were also more likely to attend gastroenterology; ear, nose and throat; urology; and dermatology, while females were more likely to be seen in plastic surgery and less likely in midwifery. Conclusions: Adding to excess risks of death and cancer, survivors of childhood ALL experience excess outpatient and inpatient activity across their TYA years, which is not related to routine follow-up monitoring. Involving most clinical specialties, associations are striking, showing no signs of diminishing over time. Recognising that ALL survivors are potentially at risk of late treatment-associated effects, our findings underscore the need to take prior ALL diagnosis into account when interpreting seemingly unrelated symptoms later in life

Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia: results of the Medical Research Council ALL 97 trial

We report on the outcome of children with Philadelphia positive acute lymphoblastic leukaemia (Ph+ ALL) treated on the UK Medical Research Council (MRC) trial for childhood ALL, MRC ALL 97, between January 1997 and June 2002. Forty-two (2·3%) patients were Ph+. Nineteen (45%) had &lt;25% blasts in bone marrow (BM) within the first 2 weeks of treatment and were defined as a good response group (GRG), the others as a poor response group (PRG). Thirty-six (86%) achieved first complete remission (CR1) at the end of induction, of which 28 underwent BM transplantation (BMT). The median follow-up was 42 months (range, 21–84). The 3-year event-free survival (EFS; 52%, 95% CI, 36–66%) was a considerable improvement on the previous MRC UKALL XI trial (27%). EFS for the GRG and PRG were 68% (43–84%) and 39% (18–59%), respectively (P = 0·03); presenting white cell count &lt;50 × 10^9/l (P = 0·02) was predictive for overall survival. Changes in the MRC ALL97 trial within the study period resulted in some Ph+ ALL receiving daunorubicin and either prednisolone or dexamethasone during induction. Though the use of daunorubicin during induction was not a prospective study question, EFS was significantly better for those whose induction included this drug (P = 0·02). Steroid randomization was not stratified for Ph+ ALL patients and was not predictive for EFS. BMT in CR1 appeared to reduce the risk of a subsequent BM relapse. These results show significant improvement on previous MRC trials; future therapeutic strategies should include early intensive therapy and BMT in CR1