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

Experiences of living with chronic myeloid leukaemia and adhering to tyrosine kinase inhibitors: A thematic synthesis of qualitative studies

Purpose: To investigate the experiences of adults living with chronic myeloid leukaemia and treated with tyrosine kinase inhibitors, with particular reference to factors influencing adherence. Methods: A thematic synthesis of all published qualitative studies examining adults with chronic myeloid leukaemia, receiving tyrosine kinase inhibitors. Eligible publications were identified by searching five electronic databases using defined criteria. The synthesis involved complete coding of extracted data and inductive theme development. Results: Nine studies were included and three overarching themes defined. Overarching themes were: 1) Disease impacts whole life; 2) Disease management strategies; and 3) Valued aspects of care. Side-effects often required physical and psychological adaptation. Patients developed individual decision-making processes to promote adherence and manage side effects. Unintentional non-adherence occurred due to forgetfulness and system failures. Intentional omission also occurred, which together with side effects, was unlikely to be reported to healthcare professionals (HCPs). HCP reassurance about missed doses could reinforce non-adherence. Information needs varied over time and between individuals. Knowledge among patients about treatment was often lacking and could lead to misunderstandings. Patients valued psychological support from HCPs and suggested an individualised approach, facilitating discussion of symptoms, adherence and their perspectives about living with chronic myeloid leukaemia, would improve care. Conclusions: Patients with chronic myeloid leukaemia experienced significant side-effects from treatment and changes to their psychological and physical well-being. They developed their own strategies to manage their disease and treatment. This should be recognised in interventions to improve education, support and the delivery of care that is compassionate and adequately resourced

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

Determinants of hospital death in haematological cancers : findings from a qualitative study

Objectives Current UK health policy promotes enabling people to die in a place they choose, which for most is home. Despite this, patients with haematological malignancies (leukaemias, lymphomas and myeloma) are more likely to die in hospital than those with other cancers, and this is often considered a reflection of poor quality end-of-life care. This study aimed to explore the experiences of clinicians and relatives to determine why hospital deaths predominate in these diseases. Methods The study was set within the Haematological Malignancy Research Network (HMRN—www.hmrn.org), an ongoing population-based cohort that provides infrastructure for evidence-based research. Qualitative interviews were conducted with clinical staff in haematology, palliative care and general practice (n=45) and relatives of deceased HMRN patients (n=10). Data were analysed for thematic content and coding and classification was inductive. Interpretation involved seeking meaning, salience and connections within the data. Results Five themes were identified relating to: the characteristics and trajectory of haematological cancers, a mismatch between the expectations and reality of home death, preference for hospital death, barriers to home/hospice death and suggested changes to practice to support non-hospital death, when preferred. Conclusions Hospital deaths were largely determined by the characteristics of haematological malignancies, which included uncertain trajectories, indistinct transitions and difficulties predicting prognosis and identifying if or when to withdraw treatment. Advance planning (where possible) and better communication between primary and secondary care may facilitate non-hospital death

Preferred and actual place of death in haematological malignancies : a report from the UK haematological malignancy research network

Objectives Hospital death is comparatively common in people with haematological cancers, but little is known about patient preferences. This study investigated actual and preferred place of death, concurrence between these and characteristics of preferred place discussions. Methods Set within a population-based haematological malignancy patient cohort, adults (≥18 years) diagnosed 2004–2012 who died 2011–2012 were included (n=963). Data were obtained via routine linkages (date, place and cause of death) and abstraction of hospital records (diagnosis, demographics, preferred place discussions). Logistic regression investigated associations between patient and clinical factors and place of death, and factors associated with the likelihood of having a preferred place discussion. Results Of 892 patients (92.6%) alive 2 weeks after diagnosis, 58.0% subsequently died in hospital (home, 20.0%; care home, 11.9%; hospice, 10.2%). A preferred place discussion was documented for 453 patients (50.8%). Discussions were more likely in women (p=0.003), those referred to specialist palliative care (p<0.001), and where cause of death was haematological cancer (p<0.001); and less likely in those living in deprived areas (p=0.005). Patients with a discussion were significantly (p<0.05) less likely to die in hospital. Last recorded preferences were: home (40.6%), hospice (18.1%), hospital (17.7%) and care home (14.1%); two-thirds died in their final preferred place. Multiple discussions occurred for 58.3% of the 453, with preferences varying by proximity to death and participants in the discussion. Conclusion Challenges remain in ensuring that patients are supported to have meaningful end-of-life discussions, with healthcare services that are able to respond to changing decisions over time

Hodgkin lymphoma detection and survival : findings from the Haematological Malignancy Research Network

Background Hodgkin lymphoma is usually detected in primary care with early signs and symptoms, and is highly treatable with standardised chemotherapy. However, late presentation is associated with poorer outcomes.Aim To investigate the relationship between markers of advanced disease, emergency admission, and survival following a diagnosis of classical Hodgkin lymphoma (CHL).Design &amp; setting The study was set within a sociodemographically representative UK population-based patient cohort of ~4 million, within which all patients were tracked through their care pathways, and linked to national data obtained from Hospital Episode Statistics (HES) and deaths.Method All 971 patients with CHL newly diagnosed between 1 September 2004–31 August 2015 were followed until 18th December 2018.Results The median diagnostic age was 41.5 years (range 0–96 years), 55.2% of the patients were male, 31.2% had stage IV disease, 43.0% had a moderate–high or high risk prognostic score, and 18.7% were admitted via the emergency route prior to diagnosis. The relationship between age and emergency admission was U-shaped: more likely in patients aged &lt;25 years and ≥70 years. Compared to patients admitted via other routes, those presenting as an emergency had more advanced disease and poorer 3-year survival (relative survival 68.4% [95% confidence interval {CI} = 60.3 to 75.2] versus 89.8% [95% CI = 87.0 to 92.0], respectively [P&lt;0.01]). However, after adjusting for clinically important prognostic factors, no difference in survival remained.Conclusion These findings suggest that CHL survival as a whole could be increased by around 4% if the cancer in patients who presented as an emergency had been detected at the same point as in other patients

The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis

The diagnosis of chronic myelomonocytic leukaemia (CMML) remains centred on morphology, meaning the distinction from a reactive monocytosis is challenging. Mutational analysis and immunophenotyping have been proposed as potential tools for diagnosis however have not been formally assessed in combination. We aimed to investigate the clinical utility of these technologies by performing targeted sequencing, in parallel to current gold standard techniques, on consecutive samples referred for investigation of monocytosis over a 2-year period (n=283). Results were correlated with the morphological diagnosis and objective outcome measures including overall survival (OS) and longitudinal blood counts. Somatic mutations were detected in 79% of patients, being invariably identified in those with a confirmed diagnosis (99%) though also in 57% of patients with non-diagnostic BM features. The OS in non-diagnostic mutated patients was indistinguishable from those with CMML (p=0.118) and significantly worse than unmutated patients (p=0.0002). On multivariate analysis age, ASXL1, CBL, DNMT3A, NRAS & RUNX1 mutations retained significance. Furthermore, the presence of a mutation was associated with a progressive fall in haemoglobin/platelet levels and increasing monocyte counts compared with mutation negative patients. Of note, the immunophenotypic features of non-diagnostic mutated patients were comparable to CMML patients and the presence of aberrant CD56 was highly specific for detecting a mutation. Overall, somatic mutations are detected at high frequency in patients referred with a monocytosis irrespective of diagnosis. In those without a WHO defined diagnosis, the mutation spectrum, immunophenotypic features and OS are indistinguishable from CMML patients and these patients should be managed as such

Using multi-state modelling to facilitate informed personalised treatment planning in Follicular Lymphoma

Follicular lymphoma is an incurable haematological cancer that tends to follow a remitting relapsing course; with treatment options ranging from “watch and wait” (active monitoring), chemotherapy, and radiotherapy. The treatment decision is typically dependent upon patient characteristics and disease stage. Using routine data collected by the Haematological Malignancy Research Network (www.hmrn.org), we are undertaking research into improving understanding of the treatment pathways and the impact of these decisions not only on the patient, but also on the cost to the healthcare provider. The aim is to facilitate informed decision making by providing a personalised prognostic tool that identifies a suitable treatment option at each stage of the treatment pathway, as part of a shared decision-making process between patient and clinician. Multi-state modelling provides an appropriate toolkit for this work, owing to its ability to predict the movement of a person through a discrete state-space captured by individual-level characteristics. This work details implementation considerations of the modelling stage, including the design of the statediagram, the fitting of transition-specific hazard functions, and the use of Discrete Event Simulation to provide estimated transition probabilities. Other considerations include how to present the results of a complex model into a deployable clinical tool