Paediatric acute lymphoblastic leukaemia and caesarean section : A report from the United Kingdom Childhood Cancer Study (UKCCS)

BACKGROUND: Reports have suggested that children born by caesarean initiated before labour onset may be at increased risk of developing acute lymphoblastic leukaemia (ALL). However, with most data being derived from case-control study interviews, information on the underpinning reasons for caesarean section is sparse, and evidence is conflicting. OBJECTIVES: Use clinical records compiled at the time of delivery to investigate the association between childhood ALL and caesarean delivery; examining timing in relation to labour onset, and reasons for the procedure. METHODS: Data are from the UK Childhood Cancer Study, a population-based case-control study conducted in the 1990s, when caesarean section rates were relatively low, in England, Scotland, and Wales. Children with ALL were individually matched to two controls on sex, date of birth, and region of residence. Information on mode of delivery and complications was abstracted from obstetric records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression models adjusted for matching variables and relevant covariates. RESULTS: Around 75% of the 1034 cases and 1914 controls were born through unassisted vaginal delivery. Caesarean delivery was as frequent in cases and controls (OR 1.07, 95% CI 0.84, 1.36). No association was observed between ALL and caesarean delivery either during or before labour, with adjusted ORs of 1.08 (95% CI 0.78, 1.48) and 1.09 (95% CI 0.78, 1.53), respectively. For B-cell ALL, the ORs were 1.14 (95% CI 0.81, 1.59) for caesarean during labour and 1.21 (95% CI 0.85, 1.72) for prelabour. The underpinning reasons for caesarean delivery differed between cases and controls; with preeclampsia, although very rare, being more common amongst cases born by caesarean (OR 8.91, 95% CI 1.48, 53.42). CONCLUSIONS: Our obstetric record-based study found no significant evidence that caesarean delivery increased the risk of childhood ALL, either overall or when carried out before labour

The long shadow of socioeconomic deprivation over the modern management of acute myeloid leukemia – time to unravel the challenges

Abstract Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with “real world” patients under-represented in clinical trials and prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease

Impact of age and socioeconomic status on treatment and survival from aggressive lymphoma : a UK population-based study of diffuse large B-cell lymphoma

AIM: To examine the influence of patient's age and socio-economic status on treatment and outcome in diffuse large B-cell lymphoma (DLBCL); an aggressive curable cancer, with an incidence rate that increases markedly with age but varies little with socio-economic status. METHODS: Set within a representative UK population of around 4 million, data are from an established patient cohort. This report includes all patients (≥18years) newly diagnosed with DLBCL 2004-2012, with follow-up to February 2015. RESULTS: Of the 2137 patients (median age 70.2 years) diagnosed with denovo DLBCL, 1709 (80%) were treated curatively/intensively and 1161(54.3%) died during follow-up. Five-year overall and relative survival (RS) estimates were 46.2% (95% CI 44.0-48.4%) and 54.6% (52.1%-57.0%) respectively for all patients, and 58.5% (56.1-60.9%) and 67.0% (64.3-69.6%) for intensively treated patients. 96.3% of patients <55 years (366/380) and 96.4% of those with the best performance status (543/563) were treated curatively: 5-year RSs being 77.9% (73.1-82%) and 87.1% (82.5-90.6%) respectively. At the other end of the age/fitness spectrum, 33.3% of those ≥85 years (66/198) and 41.1% with the worst performance (94/225) were treated curatively: the corresponding 5-year RSs being 50.5% (27.1-69.0%) and 22.9% (14.0-33.2%). The proportion of patients whose cancer was fully staged fell with increasing age and worsening performance status. No socio-economic variations with treatment, stage at presentation or outcome were detected. CONCLUSIONS: Performance status is more discriminatory of survival than chronological age, with fitter patients benefiting from treatment across all ages. Socio-economic factors are not predictive of outcome in patients with DLBCL in the UK

Estimating the prevalence of hematological malignancies and precursor conditions using data from Haematological Malignancy Research Network (HMRN)

Objective: Well-established cancer registries that routinely link to death registrations can estimate prevalence directly by counting patients alive at a particular point in time (observed prevalence). Such direct methods can only provide prevalence for the years over which the registry has been operational. Time-defined estimates, including 5- and 10-year prevalence, may however underestimate the total cancer burden, and compared with other cancers, there is a lack of accurate information on the total prevalence of hematological malignancy subtypes. Accordingly, we aimed to estimate prevalence (observed and total prevalence) of hematological malignancies and precursor conditions by clinically meaningful subtypes using data from the UK’s specialist population-based register, the Haematological Malignancy Research Network (www.hmrn.org). Methods: Observed and total prevalences were estimated from 15,810 new diagnoses of hematological malignancies from 2004 to 2011 and followed up to the 31 August 2011 (index data). Observed prevalence was calculated by the counting method, and a method based on modelling incidence and survival was used to estimate total prevalence. Estimates were made according to current disease classification for the HMRN region and for the UK. Results: The overall observed and total prevalence rates were 281.9 and 548.8 per 100,000, respectively; the total number of observed and total prevalent cases in the UK was estimated as 165,841 and 327,818 cases, as expected variation existed by disease subtype reflecting the heterogeneity in underlying disease incidence, survival and age distribution of hematological cancers. Conclusions: This study demonstrates the importance of estimating ‘total’ prevalence rather than ‘observed’ prevalence by current disease classification (ICD-O-3), particularly for subtypes that have a more indolent nature and for those that are curable. Importantly, these analyses demonstrate that relying on observed prevalence alone would result in a significant underestimation of the relative burden of some subtypes. While many of these cases may be considered cured and no longer being actively treated, people in this survivorship phase may have long-term medical needs and accordingly, it is important to provide accurate counts to allow for healthcare planning

'Unpacking' pathways to lymphoma and myeloma diagnosis : Do experiences align with the Model of Pathways to Treatment? Findings from a UK qualitative study with patients and relatives

OBJECTIVES: To explore alignment of experiences before lymphoma and myeloma diagnosis with the appraisal, help seeking and diagnostic intervals in the Model of Pathways to Treatment (MPT). DESIGN: A qualitative study using in-depth semistructured interviews with patients and relatives. Interviews were transcribed verbatim, anonymised and analysed using qualitative description. SETTING: A UK population-based haematological malignancy patient cohort. PARTICIPANTS: Fifty-five patients (35 lymphoma, 20 myeloma: diagnosed 2014-2016) and 28 relatives participated, within around a year of the patient's diagnosis. Patients were selected from those in the cohort who had returned a questionnaire about their symptoms and help seeking, and consented to contact for further research. Sampling was purposive, to achieve maximum variation in age, sex and time to diagnosis. RESULTS: Participants described time from symptom onset to diagnosis as ranging from several weeks to years. Pathways largely aligned with MPT components and help seeking could lead to the rapid investigations and identification of abnormalities. However, symptoms could be vague and/or inadvertently interpreted as other conditions, which if perpetuated, could cause diagnostic delay. The latter was associated with chaotic pathways, with activities rarely occurring only once or in a linear sequence. Rather, intermittent or ongoing processes were described, moving forward and backwards through intervals. This is 'unpacked' within five themes: (1) appraisal and reappraisal; (2) patient-initiated self-management/treatment; (3) initial help seeking; (4) re-presentation; and (5) patient-initiated actions, decisions and emotions during re-presentation. Within these themes, various healthcare professionals were consulted, often many times, as symptoms persisted/progressed. Input from family/friends was described as substantial, as was the extent to which information seeking occurred. CONCLUSION: Lymphoma and myeloma pathways align with the MPT, but do not fully capture the repetition and complexity described by participants. Time to diagnosis was often prolonged, despite the best efforts of patients, relatives and healthcare professionals. The impact of National Health Service England's Multi-diagnostic Disciplinary Centres on time to haematological cancer diagnosis remains to be seen

The Haematological Malignancy Research Network (HMRN): a new information strategy for population based epidemiology and health service research

The Haematological Malignancy Research Network (HMRN) was established in 2004 to provide robust generalizable data to inform clinical practice and research. It comprises an ongoing population-based cohort of patients newly diagnosed by a single integrated haematopathology laboratory in two adjacent UK Cancer Networks (population 3·6 million). With an emphasis on primary-source data, prognostic factors, sequential treatment/response history, and socio-demographic details are recorded to clinical trial standards. Data on 8131 patients diagnosed over the 4 years 2004–08 are examined here using the latest World Health Organization classification. HMRN captures all diagnoses (adult and paediatric) and the diagnostic age ranged from 4 weeks to 99 years (median 70·4 years). In line with published estimates, first-line clinical trial entry varied widely by disease subtype and age, falling from 59·5% in those aged <15 years to 1·9% in those aged over 75 years – underscoring the need for contextual population-based treatment and response data of the type collected by HMRN. The critical importance of incorporating molecular and prognostic markers into comparative survival analyses is illustrated with reference to diffuse-large B-cell lymphoma, acute myeloid leukaemia and myeloma. With respect to aetiology, several descriptive factors are highlighted and discussed, including the unexplained male predominance evident for most subtypes across all ages

Risk of mature B-cell neoplasms and precursor conditions after joint replacement : a report from the Haematological Malignancy Research Network

Associations between previous joint replacement and B-cell lymphoid malignancies have been reported, but despite numerous reports, associations with the disease subtypes have received little attention. Using a UK-based register of haematological malignancies and a matched general population-based cohort, joint replacements from linked hospital inpatient records were examined. Cases diagnosed 2009-2015 who were aged 50 years or more were included; 8,013 mature B-cell neoplasms comprising myeloma (n=1,763), diffuse large B-cell lymphoma (DLBCL, n=1,676), chronic lymphocytic leukaemia (CLL, n=1,594), marginal zone lymphoma (MZL, n=957), follicular lymphoma (FL, n=725), and classical Hodgkin lymphoma (CHL, n=255), together with monoclonal gammopathy of uncertain significance (MGUS, n=2,138) and monoclonal B-cell lymphocytosis (MBL, n=632). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated relative to 10 age- and sex-matched controls using conditional logistic regression. Having had a joint replacement before diagnosis was associated with myeloma (OR=1.3, 95%CI 1.1-1.5, p=0.008) and MGUS (OR=1.3, 95%CI 1.1-1.5, p<0.001). Excluding replacements in the year before diagnosis, the MGUS risk remained, elevated where two or more joints were replaced (OR=1.5, 95%CI 1.2-2.0, p=0.001), with hip (OR=1.2, 95%CI 1.0-1.5, p=0.06) or knee replacements (OR=1.5, 95%CI 1.2-1.8, p<0.001). Associations with CHL and two or more replacements (OR=2.7, 95%CI 1.3-5.6, p=0.005) or hip replacements (OR=1.9, 95%CI 1.0-3.4, p=0.04); and between DLBCL and knee replacements (OR=1.3, 95%CI 1.0-1.6, p=0.04) were also observed. This study reports for the first time a relationship between joint replacements and MGUS; while absolute risks of disease are low and not of major public health concern, these findings warrant further investigation. This article is protected by copyright. All rights reserved

A Generic Model for Follicular Lymphoma: Predicting Cost, Life Expectancy, and Quality-Adjusted-Life-Year Using UK Population–Based Observational Data

Objectives To use real-world data to develop a flexible generic decision model to predict cost, life expectancy, and quality-adjusted life-years (QALYs) for follicular lymphoma (FL) in the general patient population. Methods All patients newly diagnosed with FL in the UK’s population-based Haematological Malignancy Research Network (www.hmrn.org) between 2004 and 2011 were followed until 2015 (N = 740). Treatment pathways, QALYs, and costs were incorporated into a discrete event simulation to reflect patient heterogeneity, including age and disease management. Two scenario analyses, based on the latest National Institute for Health and Clinical Excellence (NICE) guidelines (rituximab induction therapy for newly diagnosed asymptomatic patients and rituximab maintenance therapy for patients between treatments), were conducted and their economic impacts were compared to current practice. Results Incidence-based analysis revealed expected average lifetime costs ranging from £6,165 [US$7,709] to £63,864 [US$79,862] per patient, and average life expectancy from 75 days to 17.56 years. Prevalence-based analysis estimated average annual treatment costs of £60–65 million [US$75-80 million], accounting for approximately 10$0.75-2.75 million]. Conclusions Costs, survival, and QALYs associated with FL vary markedly with patient characteristics and disease management. Allowing the production of more realistic outcomes across the patient population as a whole, our model addresses this heterogeneity and is a useful tool with which to evaluate new technologies/treatments to support healthcare decision makers