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).Design & setting The study was set within a sociodemographically representative UK population-based patient cohort of ~4 million, within which all patients were tracked through their care pathways, and linked to national data obtained from Hospital Episode Statistics (HES) and deaths.Method All 971 patients with CHL newly diagnosed between 1 September 2004–31 August 2015 were followed until 18th December 2018.Results The median diagnostic age was 41.5 years (range 0–96 years), 55.2% of the patients were male, 31.2% had stage IV disease, 43.0% had a moderate–high or high risk prognostic score, and 18.7% were admitted via the emergency route prior to diagnosis. The relationship between age and emergency admission was U-shaped: more likely in patients aged <25 years and ≥70 years. Compared to patients admitted via other routes, those presenting as an emergency had more advanced disease and poorer 3-year survival (relative survival 68.4% [95% confidence interval {CI} = 60.3 to 75.2] versus 89.8% [95% CI = 87.0 to 92.0], respectively [P<0.01]). However, after adjusting for clinically important prognostic factors, no difference in survival remained.Conclusion These findings suggest that CHL survival as a whole could be increased by around 4% if the cancer in patients who presented as an emergency had been detected at the same point as in other patients

Cohort Profile Update : The Haematological Malignancy Research Network (HMRN)’s UK population-based cohorts

Established in 2004, the Haematological Malignancy Research Network is an ongoing population-based UK cohort that is currently tracking 38 000 people diagnosed with a blood cancer or related disorder. Covering a population of ∼4 million people (14 hospitals), each year ∼2500 people enter the cohort (irrespective of age or prognosis) on the day they are diagnosed. All diagnoses are made and coded using the World Health Organization’s latest International Diseases for Oncology classification by haematopathologists at a single fully integrated laboratory. HMRN operates on a legal basis that permits all patients to be tracked through local clinical systems and linked to national administrative databases (hospital episode statistics, cancers and deaths). Patients diagnosed between 2009 and 2015 (n = 18 127) have now been matched (year of birth, sex and residency in the study area) to 10 randomly selected controls from the national population-based National Health Service Central Register. The pseudonymized comparison cohort described in this update was designed to facilitate analyses requiring general-population background rates on co-morbidities and healthcare activity

Health impact of monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL) : findings from a UK population-based cohort

Objective To examine mortality and morbidity patterns before and after premalignancy diagnosis in individuals with monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL) and compare their secondary healthcare activity to that of the general population.Design Population-based patient cohort, within which each patient is matched at diagnosis to 10 age-matched and sex-matched individuals from the general population. Both cohorts are linked to nationwide information on deaths, cancer registrations and Hospital Episode Statistics.Setting The UK’s Haematological Malignancy Research Network, which has a catchment population of around 4 million served by 14 hospitals and a central diagnostic laboratory.Participants All patients newly diagnosed during 2009–2015 with MGUS (n=2193) or MBL (n=561) and their age and sex-matched comparators (n=27 538).Main outcome measures Mortality and hospital inpatient and outpatient activity in the 5 years before and 3 years after diagnosis.Results Individuals with MGUS experienced excess morbidity in the 5 years before diagnosis and excess mortality and morbidity in the 3 years after diagnosis. Increased rate ratios (RRs) were evident for nearly all clinical specialties, the largest, both before and after diagnosis, being for nephrology (before RR=4.29, 95% CI 3.90 to 4.71; after RR=13.8, 95% CI 12.8 to 15.0) and rheumatology (before RR=3.40, 95% CI 3.18 to 3.63; after RR=5.44, 95% CI 5.08 to 5.83). Strong effects were also evident for endocrinology, neurology, dermatology and respiratory medicine. Conversely, only marginal increases in mortality and morbidity were evident for MBL.Conclusions MGUS and MBL are generally considered to be relatively benign, since most individuals with monoclonal immunoglobulins never develop a B-cell malignancy or any other monoclonal protein-related organ/tissue-related disorder. Nonetheless, our findings offer strong support for the view that in some individuals, monoclonal gammopathy has the potential to cause systemic disease resulting in wide-ranging organ/tissue damage and excess mortality

Labile plasma iron levels predict survival in patients with lower-risk Myelodysplastic syndromes

Red blood cell transfusions remain one of the cornerstones in supportive care of lower-risk patients with myelodysplastic syndromes. We hypothesized that patients develop oxidant mediated tissue injury through the formation of toxic iron species, caused either by red blood cell transfusions or by ineffective erythropoiesis. We analyzed serum samples from 100 lower-risk patients with myelodysplastic syndromes at six-month intervals for transferrin saturation, hepcidin-25, growth differentiation factor 15, soluble transferrin receptor, non-transferrin bound iron and labile plasma iron in order to evaluate temporal changes in iron metabolism and presence of potentially toxic iron species and their impact on survival. Hepcidin levels were low in 34 patients with ringed sideroblasts compared to 66 patients without. Increases of hepcidin and non-transferrin bound iron levels were visible early in follow-up of all transfusion dependent patient groups. Hepcidin levels significantly decreased over time in transfusion independent patients with ringed sideroblasts. Increased soluble transferrin receptor levels in transfusion-independent patients with ringed sideroblasts confirmed the presence of ineffective erythropoiesis and suppression of hepcidin production in these patients. Detectable labile plasma iron levels in combination with high transferrin saturation levels occurred almost exclusively in patients with ringed sideroblasts and all transfusion dependent patient groups. Detectable labile plasma iron levels in transfusion dependent patients without ringed sideroblasts were associated with decreased survival. IN CONCLUSION: toxic iron species occurred in all transfusion dependent patients and in transfusion independent patients with ringed sideroblasts. Labile plasma iron appeared to be a clinically relevant measure for potential iron toxicity and a prognostic factor for survival in transfusion dependent patients. This trial was registered at www.clinicaltrials.gov as #NCT00600860

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Frontline management of nodular lymphocyte predominant Hodgkin lymphoma - a retrospective UK multicentre study

No abstract available

Erythropoietin stimulation agents significantly improves outcome in lower risk MDS

The EUMDS Registry started in 2008 as a prospective, non-interventional longitudinal study, enrolling newly diagnosed patients with IPSS low or intermediate-1 MDS from 16 European countries and Israel