This study examined, for the first time, the relationship between place of death and time from diagnosis to death across distinct haematological malignancy sub-types. Over the eight years 2004–12, around two-thirds of all deaths within our cohort occurred in hospital, and this proportion was similar across most sub-types. Time from diagnosis to death was clearly a major determinant of place of death and, in this respect, sub-type was important. Almost 90% of patients dying within a month of diagnosis did so in hospital and these early deaths largely comprised patients with acute myeloid leukaemia, diffuse large B-cell lymphoma and myeloma. Patients surviving longer, and particularly beyond one year, were less likely to die in hospital. Our overall proportion of hospital deaths (66%) is consistent with the most recent UK national data (68%) ; and previous studies have also reported longer survival to be associated with deaths outside hospital [6, 19], although none have examined these variables by specific haematological disease sub-type.
Emanating from within an established population-based patient cohort [15, 16], the findings from this study are robust and it is likely that the patterns we observed are generalizable across the UK, and possibly to other countries with similar healthcare systems and cultural practices. Centralised diagnostics is a core aspect of our cohort, and all diagnoses are routinely coded by clinical staff to the latest WHO scheme, currently ICD-0-3 . Using these data, we were able to examine place of death by specific diagnostic sub-types, rather than adopting the more common approaches, in which these diseases have been examined either as part of the total group of cancer patients, as a component of an ‘other’ category, or within combinations of all, or certain haematological malignancies [20–25].
Importantly, this report has highlighted specific groups of patients that are ‘at risk’ of hospital death. Haematological diseases are complex, with heterogeneous pathways from diagnosis to death. Patients with acute myeloid leukaemia, diffuse large B-cell lymphoma and myeloma that die soon after diagnosis are likely to die in hospital for a number of reasons relating to their specific disease pathways. Acute myeloid leukaemia, for example, is typically associated with aggressive presentation and rapid progression. Initial hospital administered chemotherapy treatment can cause severe toxicity, including neutropenic sepsis, and there is a real possibility that sudden deterioration and death could occur as a consequence of either disease progression or the side-effects of treatment. While diffuse large B-cell lymphoma and myeloma may not always present as acutely, and treatment is often administered on an out-patient basis, it can be associated with similar toxicities to those seen with acute myeloid leukaemia. Such episodes may also result in hospital admissions, which can have the propensity end with sudden, unexpected death.
Hospital deaths in this acute context, occurring relatively unexpectedly and still within the framework of a curative/life prolonging approach to care, are arguably less avoidable than hospital deaths that occur after a longer illness. In the latter situation, where the disease has reached an anticipated terminal stage, it might be expected that there has been sufficient time to raise and discuss the subject of preferred place of care and death, and to make the appropriate arrangements. However, our results show that large numbers of patients with indolent diseases and longer survival also die in hospital, indicating that additional factors also seem to contribute to place of death.
One explanation, for this is that hospital may be the preferred place of death for some, although this has never previously been explored in patients with haematological malignancies, despite differences in the trajectories and treatment pathways of these diseases compared to other illnesses. Patients may, however, be under the care of the haematology team at the hospital over many years , during which time they often have close and sustained contact with the clinical team managing their care, leading to strong mutual relationships. A further issue to consider is that whilst we were able to identify deaths that occurred in hospital as part of this study, it is possible that some patients may have died in these settings, but on palliative care wards or in General Practitioner (GP) led local hospital wards, where the approach to care is palliative and similar to that of a hospice.
Other reasons for hospital deaths in patients with longer survival include the remitting/relapsing course of many of these diseases, which may result in treatments being given (sometimes for symptomatic relief) in the later stages of the pathway. The associated toxicities from this can again result in sudden and unexpected death, without the time to discuss place of death or plan home-discharge if this is the preferred and feasible option. Importantly, there is often a supportive element to the treatment of these diseases, including the transfusion of blood products for bone marrow failure and the administration of intravenous antibiotics for infection, both of which are generally delivered in an in-patient setting, and from which (particularly during the terminal stage of illness) the patient may not recover, thus resulting in hospital death.
Furthermore, the complexities associated with the trajectory of these diseases mean that identifying the transition from a curative to palliative approach to care can be challenging. As a consequence, clinicians have been criticised for continuing to treat advanced disease that is unlikely to respond to treatment, rather than recognising that the transition should occur [26, 27]. Further understanding of such transitions, as well as evidence to guide both patient and clinician treatment decisions (including quality of life, biological and economic data) would contribute to early treatment/care planning and may lead to a reduction in the number of hospital deaths.
Despite these difficulties increasing proportions of deaths are occurring outside hospital in patients that survive longer. As well as facilitating a defined transition and advance end-of-life care planning, longer survival is generally associated with an increased likelihood of receiving input from specialist palliative care services, which is reported to facilitate home deaths for people with both haematological cancers and solid tumours [6, 28–32]. It is not always clear whether palliative care referrals are made to facilitate home death when this is the preferred place, or whether involvement of the palliative care team facilitates discussions about end-of-life care, and exploration of the feasibility of home-death. The impact of such referrals is, however, clear and important.
Whilst we did not examine this in the present study, one factor worth considering in future projects is the impact of time-to-diagnosis on both survival and place of death. It is recognised that the time interval between symptom onset and diagnosis in patients with haematological malignancies, and especially myeloma and lymphoma, is often particularly prolonged [33–35]. Compared to people with other cancers such patients are more likely to present to hospital for the first time as an emergency, which is itself associated with poorer survival . Delayed diagnosis is also reported to lead to increased complications (such as anaemia, bone disease and renal failure in myeloma) at diagnosis  possibly requiring hospitalisation. In such circumstances, we would anticipate that some of the patients experiencing protracted time-to-diagnosis (especially those with myeloma and lymphoma) are included in the group that die soon after diagnosis and in hospital. Importantly, however, the situation is far from straight-forward and no single explanation is likely to fit all disease types; the early hospital deaths we identified will undoubtedly also include patients that experienced rapid symptom onset and diagnosis, particularly those with acute myeloid leukaemia.
Haematological malignancies are commoner in older people, and patients with these diseases may also have significant or multiple co-morbidities that contribute to their death. Although we did not examine cause of death within our study, the influence of comorbidities may be important and could in fact have a greater influence on place of death than the haematological malignancy itself; and this is particularly so for patients with more indolent disease sub-types. Whilst deaths from comorbidities undoubtedly occur in all the locations we examined, it is interesting to note the high proportion of nursing home deaths in patients with diseases that are usually monitored rather than actively treated, such as lymphoproliferative disorders (median age at diagnosis 77 years). It is likely that these patients are nursing home residents due to other comorbid/age-related factors, rather than solely because of their haematological malignancy.
Existing research has reported that home deaths are more likely to occur when home is stated as the patient’s preferred place of care . Within this study, it was not our intention to explore preferred place of care and death. This is because, along with other researchers, we have previously found great variation in the frequency and methods of documentation of such conversations, . Although standardised tools exist to facilitate discussion and documentation in primary care, we have not generally observed the use of these in secondary care settings; hand searching of hospital records for such information was beyond the scope of this present study.