Debra Howell

Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network.

Background:Ascertainment of cases and disease classification is an acknowledged problem for epidemiological research into haematological malignancies.Methods:The Haematological Malignancy Research Network comprises an ongoing population-based patient cohort. All diagnoses (paediatric and adult) across two UK Cancer Networks (population 3.6 million, >2000 diagnoses annually, socio-demographically representative of the UK) are made by an integrated haematopathology laboratory. Diagnostics, prognostics, and treatment are recorded to clinical trial standards, and socio-demographic measures are routinely obtained.Results:A total of 10 729 haematological malignancies (myeloid=2706, lymphoid=8023) were diagnosed over the 5 years, that is, from 2004 to 2009. Descriptive data (age, sex, and deprivation), sex-specific age-standardised (European population) rates, and estimated UK frequencies are presented for 24 sub-types. The age of patients ranged from 4 weeks to 99 years (median 70.6 years), and the male rate was more than double the female rate for several myeloid and lymphoid sub-types, this difference being evident in both children and adults. No relationship with deprivation was detected.Conclusion:Accurate population-based data on haematological malignancies can be collected to the standard required to deliver reproducible results that can be extrapolated to national populations. Our analyses emphasise the importance of gender and age as disease determinants, and suggest that aetiological investigations that focus on socio-economic factors are unlikely to be rewarding.

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.

Haematological malignancy: are patients appropriately referred for specialist palliative and hospice care? A systematic review and meta-analysis of published data

Haematological malignancies are complex diseases, affecting the entire age spectrum, and having marked differences in presentation, treatment, progression and outcome. Patients have a significant symptom burden and despite treatment improvements for some sub-types, many patients die from their disease. We carried out a systematic review and meta-analysis to examine the proportion of patients with haematological malignancies that received any form of specialist palliative or hospice care. Twenty-four studies were identified, nine of which were suitable for inclusion in the meta-analysis. Our review showed that patients with haematological malignancies were far less likely to receive care from specialist palliative or hospice services compared to other cancers (Risk Ratio 0.46, [95% confidence intervals 0.42–0.50]). There are several possible explanations for this finding, including: ongoing management by the haematology team and consequent strong bonds between staff and patients; uncertain transitions to a palliative approach to care; and sudden transitions, leaving little time for palliative input. Further research is needed to explore: transitions to palliative care; potential unmet patient needs; where patients want to be cared for and die; existing practices in the delivery of palliative and end-of-life care; and barriers to specialist palliative care and hospice referral and how these might be overcome.

Lymphoma incidence, survival and prevalence 2004–2014: sub-type analyses from the UK’s Haematological Malignancy Research Network

Background:Population-based information about cancer occurrence and survival are required to inform clinical practice and research; but for most lymphomas data are lacking.Methods:Set within a socio-demographically representative UK population of nearly 4 million, lymphoma data (N=5796) are from an established patient cohort.Results:Incidence, survival (overall and relative) and prevalence estimates for >20 subtypes are presented. With few exceptions, males tended to be diagnosed at younger ages and have significantly (P<0.05) higher incidence rates. Differences were greatest at younger ages: the <15 year male/female rate ratio for all subtypes combined being 2.2 (95% CI 1.3–3.4). These gender differences impacted on prevalence; most subtype estimates being significantly (P<0.05) higher in males than females. Outcome varied widely by subtype; survival of patients with nodular lymphocyte predominant Hodgkin lymphoma approached that of the general population, whereas less than a third of those with other B-cell (e.g., mantle cell) or T-cell (e.g., peripheral-T) lymphomas survived for ≥5 years. No males/female survival differences were detected.Conclusions:Major strengths of our study include completeness of ascertainment, world-class diagnostics and generalisability. The marked variations demonstrated confirm the requirement for ‘real-world’ data to inform aetiological hypotheses, health-care planning and the future monitoring of therapeutic changes.

Destined to die in hospital? Systematic review and meta-analysis of place of death in haematological malignancy

BackgroundHaematological malignancies are a common, heterogeneous and complex group of diseases that are often associated with poor outcomes despite intensive treatment. Research surrounding end-of-life issues, and particularly place of death, is therefore of paramount importance, yet place of death has not been formally reviewed in these patients.MethodsA systematic literature review and meta-analysis was undertaken using PubMed to identify all studies published between 1966 and 2010. Studies examining place of death in adult haematology patients, using routinely compiled morbidity and mortality data and providing results specific to this disease were included. 21 studies were identified with descriptive and/or risk-estimate data; 17 were included in a meta-analysis.ResultsCompared to other cancer deaths, haematology patients were more than twice as likely to die in hospital (Odds Ratio 2.25 [95% Confidence Intervals, 2.07-2.44]).ConclusionHome is generally considered the preferred place of death but haematology patients usually die in hospital. This has implications for patients who may not be dying where they wish, and also health commissioners who may be funding costly end-of-life care in inappropriate acute hospital settings. More research is needed about preferred place of care for haematology patients, reasons for hospital deaths, and how these can be avoided if home death is preferred.

What determines referral of UK patients with haematological malignancies to palliative care services? An exploratory study using hospital records

We investigated the frequency and characteristics of patients with haematological malignancies (HMs) who were, or were not, referred for specialist palliative care (SPC). Data were abstracted from hospital records of 108 patients who died — 27 with leukaemia, 11 with myelodysplastic syndromes, 48 with lymphoma and 22 with myeloma. Ninety-three patients (86.1%) were >60 years of age at diagnosis, with 33 (30.6%) being ≥80 years and 31 (28.7%) having existing comorbidities. Thirty-three patients (30.6%) were referred to SPC services. There was little difference by age or HM diagnosis in referred patients. Seventeen of 67 patients (25.4%) dying on a hospital ward received SPC compared with 6/7 (85.7%) dying at home. Time between diagnosis and death influenced the referral — 24/52 patients (46.2%) dying ≥30 days after diagnosis received SPC compared with 8/42 (19.1%) dying within 30 days. In 14 patients, HM diagnosis was confirmed after death. Identification of these 14 patients is likely to be a unique feature of our study, as patients were selected from a regional, population-based register with centralized diagnostic services, enabling the identification of all patients with HM. The interface between curative and palliative treatment in HM is more complex than the National Institute for Clinical Excellence recommendations suggest. Palliative Medicine 2007; 21 : 487—492

Determinants of survival in patients with chronic myeloid leukaemia treated in the new era of oral therapy: findings from a UK population-based patient cohort

Objectives To examine contemporary survival patterns in the general population of patients diagnosed with chronic myeloid leukaemia (CML), and to identify patient groups with less than optimal outcomes. Design Prospective population-based cohort. Setting The UKs Haematological Malignancy Research Network (catchment population 3.6 million, with >2000 new haematological malignancies diagnosed annually). Participants All patients newly diagnosed with CML, from September 2004 to August 2011 and followed up to 31 March 2013. Main outcome measure Incidence and survival. Results With a median diagnostic age of 59 years, the CML age standardised (European) incidence was 0.9/100 000 (95% CIs 0.8 to 0.9), 5-year overall survival was 78.9% (72.3 to 84.0) and 5-year relative survival 88.6% (81.0 to 93.3). The efficacy of treatment across all ages was clearly demonstrated; the relative survival curves for those under 60 and over 60 years being closely aligned. Survival findings were similar for men and women, but varied with deprivation; the age and sex adjusted HR being 3.43 (1.89 to 6.22) for deprivation categories 4–5 (less affluent) versus 1–3 (more affluent). None of these differences were attributable to the biological features of the disease. Conclusions When therapy is freely provided, population-based survival for CML is similar to that reported in clinical trials, and age loses its prognostic significance. However, although most of the patients with CML now experience close to normal lifespans, those living in more deprived areas tend to have poorer outcomes, despite receiving the same clinical care. A significant improvement in overall population outcomes could be achieved if these socioeconomic differences, which may reflect the treatment compliance, could be eliminated.

Non‐Hodgkin lymphoma and autoimmunity: Does gender matter?

Autoimmune disorders are more frequent in women, whereas most non‐Hodgkin lymphomas (NHLs) are common in men; yet, sex‐specific autoimmune–lymphoma associations are rarely reported. Detailed data on autoimmune disease were abstracted from medical records of 791 cases (including 316 diffuse large B‐cell lymphomas (DLBCLs); 228 follicular lymphomas (FLs); 127 marginal zone lymphomas (MZLs); 64 T‐cell lymphomas and 38 mantle cell lymphomas) and 872 controls. The combined prevalence of autoimmune disease was higher among women (15.7% controls; 19.7% cases) than men (6.6% controls; 14.5% cases), but the overall association with NHL was stronger for men (odds ratio 2.4, 95% confidence interval: 1.5–3.8) than women (1.3, 0.9–1.9), the disparity persisting when data for the year immediately preceding lymphoma diagnosis were excluded (men 2.0, 1.3–3.3; women 1.2, 0.8–1.8). For both sexes, the strongest individual associations were for DLBCL, MZL and T‐cell lymphomas, with no associations evident for FL. Among women, there were strong links between MZL and both Sjögrens syndrome and idiopathic thrombocytopenia, and among men, between DLBCL and both rheumatoid arthritis and Crohns disease. The expected association between coeliac disease and T‐cell lymphoma was seen in both sexes. Our results add to the accumulating knowledge on this topic and suggest that future studies should analyze data for men and women separately.

Help‐seeking behaviour in patients with lymphoma

Reducing cancer mortality is a priority for the UK Government and emphasis has been placed on introducing targets to ensure prompt diagnosis. Help seeking is the first step on the pathway to diagnosis and should occur promptly; however, patients with lymphoma take longer to seek help for symptoms than those with many other cancers. Despite this, the help seeking behaviour of these patients has not been investigated. This qualitative study examined the beliefs and actions about help seeking among 32 patients, aged 65 and over and newly diagnosed with lymphoma in West Yorkshire during 2000. Patients reported an extremely wide range of symptoms which were not always interpreted as serious or potentially caused by cancer. This, in association with a clear lack of knowledge about lymphoma, often led to help seeking being deferred. The range and characteristics of symptoms can largely be explained in terms of variations in the type, site and size of the lymphoma. The UK Government targets focus on the time after help seeking, yet for lymphoma it is also crucial to reduce the time taken to seek help. More education about the potential symptoms of this disease is needed among the general public.

Variations in specialist palliative care referrals: findings from a population-based patient cohort of acute myeloid leukaemia, diffuse large B-cell lymphoma and myeloma

Objective To develop and implement a methodology for capturing complete haematological malignancy pathway data and use it to identify variations in specialist palliative care (SPC) referrals. Methods In our established UK population-based patient cohort, 323 patients were diagnosed with acute myeloid leukaemia, diffuse large B-cell lymphoma or myeloma between May 2005 and April 2008, and died before April 2010. A day-by-day calendar approach was devised to collect pathway data, including SPC referrals, to supplement routinely collected information on clinical presentation, diagnosis, treatment, response, and date and place of death. Results 155 (47.9%) of the 323 patients had at least one SPC referral. The likelihood of referral increased with survival (OR 6.58, 95% CIs 3.32 to 13.03 for patients surviving ≥1 year compared to ≤1 month from diagnosis), and varied with diagnosis (OR 1.96, CIs 1.15 to 3.35 for myeloma compared to acute myeloid leukaemia). Compared to patients dying in hospital, those who died at home or in a hospice were also more likely to have had an SPC referral (OR 3.07, CIs 1.59 to 5.93 and 4.74, CIs 1.51 to 14.81, respectively). No associations were found for age and sex. Conclusions Our novel approach efficiently captured pathway data and SPC referrals, revealing evidence of greater integration between haematology and SPC services than previously reported. The likelihood of referral was much higher among those dying outside hospital, and variations in practice were observed by diagnosis, emphasising the importance of examining diseases individually.