The epidemiology of leukaemia in the UK

INTRODUCTION Approximately 9% of all new malignant diagnoses in the UK are due to haematological malignancies. The acute and chronic leukaemias constitute 2.5 % of all cancers and leukaemia is the 12th most common cancer registered in the UK. Approximately 7 000 people are diagnosed with the disease and more than 4 300 people die from leukaemia in the UK each year. As such, they have an important impact on the health of the public and represent a significant cost to the health care budget. AIMS AND OBJECTIVES The research presented in this thesis firstly aimed to quantify the incidence of and mortality from the acute and chronic leukaemias in the UK, and to define their associations with gender, age, socioeconomic class, calendar time, and geographic region of residence. A further aim was to determine whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) had a protective effect on the incidence of and mortality from these leukaemias, as has been shown to be the case for a number of other cancers. Finally, the impact of alcohol consumption on leukaemia incidence and mortality was investigated. A surprising result from the incidence and mortality studies was that survival in AML, but not other leukaemias, was worse with increasing socioeconomic deprivation. This generated an additional hypothesis surrounding potential class bias in bone marrow transplantation in these patients, a new area that was also investigated, in addition to the original aims and objectives of the research. METHODS Both general practice and hospital data were used to conduct these population-based studies. 'The Health Improvement Network' (THIN) general practice dataset was used to conduct the cohort studies of incidence and mortality, as well the case-control studies investigating non-steroidal anti-inflammatory drug use and alcohol consumption, as potential risk factors for leukaemia. Hospital Episode Statistics (HES) data were used to investigate the additional hypothesis generated by results of the incidence and mortality studies, which showed that mortality in AML patients worsens with increasing socioeconomic deprivation. RESULTS A total of 4162 cases of leukaemia were identified, 2314 (56%) of whom were male. The overall incidence of leukaemia is 11.25 per 100 000 person-years and is independent of socioeconomic class. Median survival from leukaemia is 6.58 years and mortality increases with increasing age at diagnosis. The prognosis in AML is dismal and worsens with increasing socioeconomic deprivation, a phenomenon not seen in other leukaemias. Bone marrow transplantation declines with increasing socioeconomic deprivation (p for trend <0.01). Patients with AML in the most deprived socioeconomic quintile are 40% less likely to have a bone marrow transplantation than those in the most advantaged socioeconomic class (OR 0.60, p<0.01, 95% C.I. 0.49 - 0.73), even after adjusting for gender, age at diagnosis, year of bone marrow transplantation and co-morbidity. The risk of leukaemia overall appears to increase marginally with increased use of NSAIDs prior to diagnosis. This is not seen when individual leukaemia subtypes are examined, however, except perhaps in CLL where patients who had received 2-5 prescriptions/year were 29% more likely to be diagnosed with CLL than those who had not had any NSAID prescriptions (O.R. 1.29, p=0.05, 95% C.I. 1.00 - 1.67). There is no statistically significant association between exposure to NSAIDs prior to leukaemia diagnosis, and survival. There is no statistically significant association between alcohol consumptionand risk of developing leukaemia overall, nor with any of the leukaemia subtypes studied here. Alcohol consumption is associated with a lower risk of death in leukaemia overall (HR 0.83, p=0.04, 95% C.I. 0.69 - 0.99), as well as in All (HR 0.14, p<0.01, 95% C.I. 0.04 - 0.44) and CLL (HR 0.71, p=0.02, 95% C.1. 0.53 - 0.96), when compared to those who had not consumed any alcohol

Bone marrow transplantation in AML, and socioeconomic class: a UK population-based cohort study

<p>Abstract</p> <p>Background</p> <p>We have previously shown that in the UK mortality in people with Acute Myeloid Leukaemia (AML) was nearly 50% greater among the most socio-economically deprived. The aim of this study was to determine whether AML patients from lower socioeconomic classes had a lower chance of receiving a bone marrow transplant.</p> <p>Methods</p> <p>Using Hospital Episode Statistics (HES) data, we identified all incident cases of AML admitted to UK hospitals between 1998 and 2007. We calculated the number of bone marrow transplantations undertaken in AML patients, stratifying our results by gender, age at diagnosis, year of diagnosis, degree of socioeconomic deprivation and co-morbidity. We used logistic regression to calculate odds ratios for bone marrow transplantation, adjusting for gender, age at diagnosis, year of diagnosis, degree of socioeconomic deprivation and co-morbidity score.</p> <p>Results</p> <p>We identified a total of 23 910 incident cases of AML over this 10-year time period, of whom 1 140 (4.8%) underwent BMT. Bone marrow transplantation declined with increasing socioeconomic deprivation (p for trend < 0.001) such that people in the most deprived socioeconomic quintile were 40% less likely to have a transplant than those in the most advantaged group (Odds Ratio 0.60, 95% confidence interval 0.49, 0.73), even after adjusting for gender, age at diagnosis, year of diagnosis and co-morbidity.</p> <p>Conclusion</p> <p>This large cohort study demonstrates that AML patients from lower socioeconomic classes are less likely to undergo bone marrow transplantation than their better off counter-parts.</p

What is the risk of progressive multifocal leukoencephalopathy in patients with ulcerative colitis or Crohn’s Disease treated with vedolizumab?

Background: Progressive multifocal leukoencephalopathy is a serious condition linked to certain diseases and immunosuppressant therapies, including the α4 integrin antagonist natalizumab. No cases have been reported to date with vedolizumab, a selective antagonist of the α4β7 integrin expressed on gut-homing lymphocytes. This analysis aimed to describe the current and future expected occurrence of progressive multifocal leukoencephalopathy with vedolizumab use, were the risk the same as in other populations in which this disease has been studied. Methods: The expected number of vedolizumab-associated progressive multifocal leukoencephalopathy cases was estimated up to May 19, 2016 and modelled up to 2034. These estimates were based on the cumulative exposure to the drug, assuming an equivalent risk to that of patients treated with natalizumab or those from other reference populations where progressive multifocal leukoencephalopathy has been examined. Future cases were modelled based on similar risks and projected sales. Results: The cumulative vedolizumab exposure was estimated at 54,619 patient-years, with a 95% confidence interval of 0.0–6.75 cases per 100,000 patient-years. An estimated 30.2 (95% confidence interval 19.4–40.9) cases of progressive multifocal leukoencephalopathy would have occurred if vedolizumab had the same risk as that of natalizumab. There would be a 50% chance of the first case occurring by 2018, assuming an equivalent risk to the general population. Conclusions: These analyses indicate the risk of progressive multifocal leukoencephalopathy with vedolizumab is small, and unlikely to be above 6.75 cases per 100,000 patient-years

The epidemiology of leukaemia in the UK

INTRODUCTION Approximately 9% of all new malignant diagnoses in the UK are due to haematological malignancies. The acute and chronic leukaemias constitute 2.5 % of all cancers and leukaemia is the 12th most common cancer registered in the UK. Approximately 7 000 people are diagnosed with the disease and more than 4 300 people die from leukaemia in the UK each year. As such, they have an important impact on the health of the public and represent a significant cost to the health care budget. AIMS AND OBJECTIVES The research presented in this thesis firstly aimed to quantify the incidence of and mortality from the acute and chronic leukaemias in the UK, and to define their associations with gender, age, socioeconomic class, calendar time, and geographic region of residence. A further aim was to determine whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) had a protective effect on the incidence of and mortality from these leukaemias, as has been shown to be the case for a number of other cancers. Finally, the impact of alcohol consumption on leukaemia incidence and mortality was investigated. A surprising result from the incidence and mortality studies was that survival in AML, but not other leukaemias, was worse with increasing socioeconomic deprivation. This generated an additional hypothesis surrounding potential class bias in bone marrow transplantation in these patients, a new area that was also investigated, in addition to the original aims and objectives of the research. METHODS Both general practice and hospital data were used to conduct these population-based studies. 'The Health Improvement Network' (THIN) general practice dataset was used to conduct the cohort studies of incidence and mortality, as well the case-control studies investigating non-steroidal anti-inflammatory drug use and alcohol consumption, as potential risk factors for leukaemia. Hospital Episode Statistics (HES) data were used to investigate the additional hypothesis generated by results of the incidence and mortality studies, which showed that mortality in AML patients worsens with increasing socioeconomic deprivation. RESULTS A total of 4162 cases of leukaemia were identified, 2314 (56%) of whom were male. The overall incidence of leukaemia is 11.25 per 100 000 person-years and is independent of socioeconomic class. Median survival from leukaemia is 6.58 years and mortality increases with increasing age at diagnosis. The prognosis in AML is dismal and worsens with increasing socioeconomic deprivation, a phenomenon not seen in other leukaemias. Bone marrow transplantation declines with increasing socioeconomic deprivation (p for trend <0.01). Patients with AML in the most deprived socioeconomic quintile are 40% less likely to have a bone marrow transplantation than those in the most advantaged socioeconomic class (OR 0.60, p<0.01, 95% C.I. 0.49 - 0.73), even after adjusting for gender, age at diagnosis, year of bone marrow transplantation and co-morbidity. The risk of leukaemia overall appears to increase marginally with increased use of NSAIDs prior to diagnosis. This is not seen when individual leukaemia subtypes are examined, however, except perhaps in CLL where patients who had received 2-5 prescriptions/year were 29% more likely to be diagnosed with CLL than those who had not had any NSAID prescriptions (O.R. 1.29, p=0.05, 95% C.I. 1.00 - 1.67). There is no statistically significant association between exposure to NSAIDs prior to leukaemia diagnosis, and survival. There is no statistically significant association between alcohol consumptionand risk of developing leukaemia overall, nor with any of the leukaemia subtypes studied here. Alcohol consumption is associated with a lower risk of death in leukaemia overall (HR 0.83, p=0.04, 95% C.I. 0.69 - 0.99), as well as in All (HR 0.14, p<0.01, 95% C.I. 0.04 - 0.44) and CLL (HR 0.71, p=0.02, 95% C.1. 0.53 - 0.96), when compared to those who had not consumed any alcohol.EThOS - Electronic Theses Online ServiceGBUnited Kingdo