Patient perspectives of 'Watch and Wait' for chronic haematological cancers: Findings from a qualitative study.

Purpose: Chronic blood cancers are incurable, and characterised by unpredictable, remitting-relapsing pathways. Management often involves periods of observation prior to treatment (if required), and post-treatment, in an approach known as 'Watch and Wait'. This study aimed to explore patient experiences of 'Watch and Wait'.

Incurable but treatable: Understanding, uncertainty and impact in chronic blood cancers-A qualitative study from the UK's Haematological Malignancy Research Network.

Objective: Most blood cancers are incurable and typically follow unpredictable remitting-relapsing pathways associated with varying need for treatment, which may be distressing for patients. Our objective was to conduct a qualitative study to explore understanding among patients with such malignancies, including the explanations given by HCPs and the impact of uncertain trajectories, to generate evidence that could guide improvements in clinical practice.

Methods: The study is set within a population-based patient cohort (the Haematological Malignancy Research Network), in which care is delivered across 14 hospitals according to national guidelines.

BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver.

Mitophagy formed the basis of the original description of autophagy by Christian de Duve when he demonstrated that GCG (glucagon) induced macroautophagic/autophagic turnover of mitochondria in the liver. However, the molecular basis of liver-specific activation of mitophagy by GCG, or its significance for metabolic stress responses in the liver is not understood. Here we show that BNIP3 is required for GCG-induced mitophagy in the liver through interaction with processed LC3B; an interaction that is also necessary to localize LC3B out of the nucleus to cytosolic mitophagosomes in response to nutrient deprivation.

Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes.

Tumor protein p53 (TP53) is the most frequently mutated gene in cancer. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease, rapid transformation to acute myeloid leukemia (AML), resistance to conventional therapies and dismal outcomes. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations.

Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report.

Based on the profile of genetic alterations occurring in tumor samples from selected diffuse large B-cell lymphoma (DLBCL) patients, 2 recent whole-exome sequencing studies proposed partially overlapping classification systems. Using clustering techniques applied to targeted sequencing data derived from a large unselected population-based patient cohort with full clinical follow-up (n = 928), we investigated whether molecular subtypes can be robustly identified using methods potentially applicable in routine clinical practice. DNA extracted from DLBCL tumors diagnosed in patients residing in a catchment population of ∼4 million (14 centers) were sequenced with a targeted 293-gene hematological-malignancy panel.

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).

Blood transfusion history and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis.

Purpose: To conduct a pooled analysis assessing the association of blood transfusion with risk of non-Hodgkin lymphoma (NHL).

Methods: We used harmonized data from 13 case-control studies (10,805 cases, 14,026 controls) in the InterLymph Consortium. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusted for study design variables.

Haematology nurses' perspectives of their patients' places of care and death: A UK qualitative interview study.

Purpose: 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.

Method: Qualitative description, based on thematic content analysis.

Perspectives of bereaved relatives of patients with haematological malignancies concerning preferred place of care and death: A qualitative study.

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.

Disease-related factors affecting timely lymphoma diagnosis: a qualitative study exploring patient experiences.

Background: Expediting cancer diagnosis is widely perceived as one way to improve patient outcomes. Evidence indicates that lymphoma diagnosis is often delayed, yet understanding of issues influencing this is incomplete.

Aim: To explore patients' and their relatives' perceptions of disease-related factors affecting time to diagnosis of Hodgkin and non-Hodgkin lymphoma.

Autophagy, cancer stem cells and drug resistance.

Autophagy is a cellular survival mechanism that is induced by cancer therapy, among other stresses, and frequently contributes to cancer cell survival during long periods of dormancy and the eventual outgrowth of metastatic disease. Autophagy degrades large cellular structures that, once broken down, contribute to cellular survival through the recycling of their constituent metabolites. However, the extent to which this fuel function of autophagy is key to its role in promoting stemness, dormancy and drug resistance remains to be determined.

Myeloma: Patient accounts of their pathways to diagnosis.

Background: Pathways to myeloma diagnosis can be prolonged, and are often preceded by multiple GP consultations and emergency presentation. This is the first qualitative study to examine events leading to diagnosis by asking patients about their experiences during this time.

Methods: Set within a UK population-based cohort, semi-structured interviews were conducted with 20 myeloma patients with varying characteristics and pathways, 12 of whom invited their relatives to take part.

Palliative care specialists' perceptions concerning referral of haematology patients to their services: findings from a qualitative study.

Background: 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.

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.

Risk factors and time to symptomatic presentation in leukaemia, lymphoma and myeloma.

Background: UK policy aims to improve cancer outcomes by promoting early diagnosis, which for many haematological malignancies is particularly challenging as the pathways leading to diagnosis can be difficult and prolonged.

Methods: A survey about symptoms was sent to patients in England with acute leukaemia, chronic lymphocytic leukaemia (CLL), chronic myeloid leukaemia (CML), myeloma and non-Hodgkin lymphoma (NHL). Symptoms and barriers to first help seeking were examined for each subtype, along with the relative risk of waiting >3 months' time from symptom onset to first presentation to a doctor, controlling for age, sex and deprivation.

Multiplexed metagenome mining using short DNA sequence tags facilitates targeted discovery of epoxyketone proteasome inhibitors.

In molecular evolutionary analyses, short DNA sequences are used to infer phylogenetic relationships among species. Here we apply this principle to the study of bacterial biosynthesis, enabling the targeted isolation of previously unidentified natural products directly from complex metagenomes. Our approach uses short natural product sequence tags derived from conserved biosynthetic motifs to profile biosynthetic diversity in the environment and then guide the recovery of gene clusters from metagenomic libraries.

Medical history, lifestyle, family history, and occupational risk factors for follicular lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

Background: Follicular lymphoma (FL) has been linked with cigarette smoking and, inconsistently, with other risk factors.

Methods: We assessed associations of medical, hormonal, family history, lifestyle, and occupational factors with FL risk in 3530 cases and 22639 controls from 19 case-control studies in the InterLymph consortium. Age-, race/ethnicity-, sex- and study-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.

Place of death in haematological malignancy: variations by disease sub-type and time from diagnosis to death.

Background: 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.

Methods: 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.

Time-to-diagnosis and symptoms of myeloma, lymphomas and leukaemias: a report from the Haematological Malignancy Research Network.

Background: Prior to diagnosis, patients with haematological cancers often have multiple primary care consultations, resulting in diagnostic delay. They are less likely to be referred urgently to hospital and often present as emergencies. We examined patient perspectives of time to help-seeking and diagnosis, as well as associated symptoms and experiences.

Childhood acute lymphoblastic leukaemia and birthweight: insights from a pooled analysis of case-control data from Germany, the United Kingdom and the United States.

Background: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes (<1500 and > 4500 g), we pooled data from three of the largest childhood cancer case-control studies ever conducted.

Methods: Birthweight and gestational age on 4075 children with ALL and 12,065 controls were collected during the course of three studies conducted in the USA, the UK and Germany in the 1990s.

Epidemiology of lymphomas.

Epidemiological reports on lymphomas often begin, and sometimes end, by stating that little is known about the causes of the condition(s) under study. This is slowly changing as information on the pathological diversity of subtypes accumulates. This review examines the epidemiology of lymphomas, focusing on the impact of the latest World Health Organization (WHO) classification.