Treatment options for patients with Waldenström macroglobulinemia (WM) and closely related disorders include alkylating agents, purine analogs, and monoclonal antibodies. No large randomized studies ...have yet been reported comparing any of these approaches.
The randomized WM1 study (Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia) was undertaken in 101 centers in five countries enrolling 414 eligible patients (339 with WM, 37 with non-mucosa-associated lymphoid tissue marginal zone lymphoma, and 38 with lymphoplasmacytic lymphoma) who were randomly assigned to receive chlorambucil or fludarabine. The primary end point was the overall response rate (ORR).
On the basis of intent-to-treat analysis, the ORR was 47.8% (95% CI, 40.9% to 54.8%) in the fludarabine arm versus 38.6% (95% CI, 32.0% to 45.7%) in the chlorambucil arm (P = .07). With a median follow-up of 36 months (interquartile range, 18 to 58 months), median progression-free survival (PFS), and duration of response (DR) were significantly improved in the fludarabine arm compared with the chlorambucil arm: PFS, 36.3 versus 27.1 months (P = .012) and DR, 38.3 versus 19.9 months (P < .001). In patients with WM, median overall survival (OS) was not reached in the fludarabine arm versus 69.8 months in the chlorambucil arm (95% CI, 61.6 to 79.8 months; P = .014). Grade 3 to 4 neutropenia was significantly higher among patients treated with fludarabine (36%) compared with patients treated with chlorambucil (17.8%; P < .001). Second malignancies were significantly more frequent in the chlorambucil arm with 6-year cumulative incidence rate of 20.6% versus 3.7% in the fludarabine arm (P = .001).
In the complete intent-to-treat study population, fludarabine significantly improved PFS compared with chlorambucil, and in patients with WM, it improved OS.
Haematological malignancies (leukaemias, lymphomas and myeloma) are complex cancers that are relatively common, affect all ages and have divergent outcomes. Although the symptom burden of these ...diseases is comparable to other cancers, patients do not access specialist palliative care (SPC) services as often as those with other cancers. To determine the reasons for this, we asked SPC practitioners about their perspectives regarding the barriers and facilitators influencing haematology patient referrals.
We conducted a qualitative study, set within the United Kingdom's (UK's) Haematological Malignancy Research Network (HMRN: www.hmrn.org ), a population-based cohort in the North of England. In-depth, semi-structured interviews were conducted with 20 SPC doctors and nurses working in hospital, community and hospice settings between 2012 and 2014. Interviews were digitally audio-recorded, transcribed and analysed for thematic content using the 'Framework' method.
Study participants identified a range of barriers and facilitators influencing the referral of patients with haematological malignancies to SPC services. Barriers included: the characteristics and pathways of haematological malignancies; the close patient/haematology team relationship; lack of role clarity; late end of life discussions and SPC referrals; policy issues; and organisational issues. The main facilitators identified were: establishment of inter-disciplinary working patterns (co-working) and enhanced understanding of roles; timely discussions with patients and early SPC referral; access to information platforms able to support information sharing; and use of indicators to 'flag' patients' needs for SPC. Collaboration between haematology and SPC was perceived as beneficial and desirable, and was said to be increasing over time.
This is the first UK study to explore SPC practitioners' perceptions concerning haematology patient referrals. Numerous factors were found to influence the likelihood of referral, some of which related to the organisation and delivery of SPC services, so were amenable to change, and others relating to the complex and unique characteristics and pathways of haematological cancers. Further research is needed to assess the extent to which palliative care is provided by haematology doctors and nurses and other generalists and ways in which clinical uncertainty could be used as a trigger, rather than a barrier, to referral.
Background:
People with haematological malignancies have different end-of-life care patterns from those with other cancers and are more likely to die in hospital. Little is known about patient and ...relative preferences at this time and whether these are achieved.
Aim:
To explore the experiences and reflections of bereaved relatives of patients with leukaemia, lymphoma or myeloma, and examine (1) preferred place of care and death; (2) perceptions of factors influencing attainment of preferences; and (3) changes that could promote achievement of preferences.
Design:
Qualitative interview study incorporating ‘Framework’ analysis.
Setting/participants:
A total of 10 in-depth interviews with bereaved relatives.
Results:
Although most people expressed a preference for home death, not all attained this. The influencing factors include disease characteristics (potential for sudden deterioration and death), the occurrence and timing of discussions (treatment cessation, prognosis, place of care/death), family networks (willingness/ability of relatives to provide care, knowledge about services, confidence to advocate) and resource availability (clinical care, hospice beds/policies). Preferences were described as changing over time and some family members retrospectively came to consider hospital as the ‘right’ place for the patient to have died. Others shared strong preferences with patients for home death and acted to ensure this was achieved. No patients died in a hospice, and relatives identified barriers to death in this setting.
Conclusion:
Preferences were not always achieved due to a series of complex, interrelated factors, some amenable to change and others less so. Death in hospital may be preferred and appropriate, or considered the best option in hindsight.
Patients with haematological malignancies are more likely to die in hospital, and less likely to access palliative care than people with other cancers, though the reasons for this are not well ...understood. The purpose of our study was to explore haematology nurses' perspectives of their patients’ places of care and death.
Qualitative description, based on thematic content analysis. Eight haematology nurses working in secondary and tertiary hospital settings were purposively selected and interviewed. Transcriptions were coded and analysed for themes using a mainly inductive, cross-comparative approach.
Five inter-related factors were identified as contributing to the likelihood of patients’ receiving end of life care/dying in hospital: the complex nature of haematological diseases and their treatment; close clinician-patient bonds; delays to end of life discussions; lack of integration between haematology and palliative care services; and barriers to death at home.
Hospital death is often determined by the characteristics of the cancer and type of treatment. Prognostication is complex across subtypes and hospital death perceived as unavoidable, and sometimes the preferred option. Earlier, frank conversations that focus on realistic outcomes, closer integration of palliative care and haematology services, better communication across the secondary/primary care interface, and an increase in out-of-hours nursing support could improve end of life care and facilitate death at home or in hospice, when preferred.
•Patients with haematological malignancies are more likely to die in hospital than people with other cancers.•No previous research has reported on UK haematology nurses' perspectives of their patients' place of care and place of death.•Hospital deaths were largely attributed to disease characteristics, nature of treatment and difficulties with prognostication.•However, other modifiable factors were also identified as barriers to death at home.
The International Prognostic Index (IPI) identifies poor- and good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an ...uncertain prognosis. To determine whether cellular factors can be combined with the IPI to more accurately predict outcome, we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53 gene band shifts were detected using single-stranded conformational polymorphism polymerase chain reaction analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R = 0.22, P < .0001) and bcl-2 (R = 0.14, P = .0001) were independent poor prognostic factors and a GC phenotype predicted a favorable outcome (R = −0.025, P = .02). Neither p53 expression nor band shifts had a significant effect on survival. Using the IPI alone, 8% of patients were identified as high risk. Expression of bcl-2 in the intermediate IPI group identified a further 28% of patients with an overall survival comparable to the high IPI group. In the intermediate IPI, bcl-2− group, the presence of a GC phenotype improved overall survival to levels approaching the IPI low group. Following this analysis only 15% of patients failed to be assigned to a favorable- or poor-risk group. Sequential addition of bcl-2 expression and GC phenotype into the IPI significantly improves risk stratification in DLBCL. For the 36% of high-risk patients with a 2-year overall survival of 19%, alternative treatment strategies should be considered in future trials.
The reasons patients with haematological malignancies die in hospital more often than those with other cancers is the subject of much speculation. We examined variations in place of death by disease ...sub-type and time from diagnosis to death, to identify groups of 'at-risk' patients.
The study is based in the United Kingdom within the infrastructure of the Haematological Malignancy Research Network (HMRN), a large on-going population-based cohort including all patients newly diagnosed with haematological malignancies in the north of England. Diagnostic, demographic, prognostic, treatment and outcome data are collected for each patient and individuals are 'flagged' for death. This study includes all adults (≥18 years) diagnosed 1st September 2004 to 31st August 2010 (n = 10,325), focussing on those who died on/before 31st August 2012 (n = 4829).
Most deaths occurred in hospital (65.9%), followed by home (15.6%), nursing home (11%) and hospice (7.5%) and there was little variation by diagnostic sub-type overall. Differences in place of death were, however, observed by time from diagnosis to death, and this was closely related to sub-type; 87.7% of deaths within a month of diagnosis happened in hospital and these largely occurred in patients with acute myeloid leukaemia, diffuse large B-cell lymphoma and myeloma. Patients surviving longer, and particularly beyond 1 year, were less likely to die in hospital and this corresponded with an increase in the proportion of home deaths.
Time from diagnosis to death was clearly a major determinant of place of death and many patients that died within three months of diagnosis did so in hospital. This was closely related to disease sub-type, with early deaths occurring most notable in the more aggressive diseases. This is likely to be due to a combination of factors including acute presentation, rapid disease progression without transition to a palliative approach to care and complications of treatment. Nonetheless, hospital deaths also occurred frequently in indolent diseases, suggesting that other factors were likely to contribute to the large proportion of hospital deaths overall. More evidence is needed to fully understand these complex cancers.
Abstract Background Acute myeloid leukemia (AML) can be diagnosed at any age and treatment, which can be given with supportive and/or curative intent, is considered expensive compared with that for ...other cancers. Despite this, no long-term predictive models have been developed for AML, mainly because of the complexities associated with this disease. Objective The objective of the current study was to develop a model (based on a UK cohort) to predict cost and life expectancy at a population level. Methods The model developed in this study combined a decision tree with several Markov models to reflect the complexity of the prognostic factors and treatments of AML. The model was simulated with a cycle length of 1 month for a time period of 5 years and further simulated until age 100 years or death. Results were compared for two age groups and five different initial treatment intents and responses. Transition probabilities, life expectancies, and costs were derived from a UK population-based specialist registry—the Haematological Malignancy Research Network ( www.hmrn.org ). Results Overall, expected 5-year medical costs and life expectancy ranged from £8,170 to £81,636 and 3.03 to 34.74 months, respectively. The economic and health outcomes varied with initial treatment intent, age at diagnosis, trial participation, and study time horizon. The model was validated by using face, internal, and external validation methods. The results show that the model captured more than 90% of the empirical costs, and it demonstrated good fit with the empirical overall survival. Conclusions Costs and life expectancy of AML varied with patient characteristics and initial treatment intent. The robust AML model developed in this study could be used to evaluate new diagnostic tools/treatments, as well as enable policy makers to make informed decisions.
(1) Rats were fed on diets enriched with sucrose, beef tallow or corn oil and treated for 11-16 days with 50 mg of benfluorex per kg of body weight. By these times the growth rate and food intake ...were not significantly different from those of control rats. (2) Benfluorex approximately halved the concentration of circulating triacylglycerol in rats fed the beef tallow or sucrose diets. (3) It did not significantly alter the total lipoprotein lipase activity in diaphragm, heart and adipose tissue. (4) The clearance of triacylglycerols from chylomicrons exhibited two t 1/2 values of about 0.6 and 6.9 min in rats fed the beef tallow diet. Benfluorex did not significantly alter these values. (5) Benfluorex did not significantly alter the rate of appearance of triacylglycerol in the blood of rats injected with Triton WR 1339 to block triacylglycerol uptake. It did, however, decrease the rise in circulating glucose which presumably resulted from the stress of the procedure. (6) Benfluorex decreased the extent and duration of the rise in serum corticosterone when rats maintained on the corn oil diet were fed acutely with fructose. It also decreased the circulating concentrations of glycerol, triacylglycerol and glucose after fructose feeding. (7) Rats fed on the corn oil diet and then treated with benfluorex had lower concentrations of circulating glucose, triacylglycerol, glycerol and fatty acids after being injected with 2-deoxyglucose. (8) It is proposed that some of the long-term hypoglycaemic and hypotriglyceridaemic effects of benfluorex could be mediated indirectly through changes in endocrine balance, perhaps via the serotonergic system and in particular, by decreasing the effects of stress hormones relative to insulin. The implications of these findings are discussed in relation to controlling metabolism in stress conditions and for the management of obesity, diabetes and atherosclerosis.
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