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. Bernoulli mixture-model clustering was applied and the resulting subtypes analyzed in relation to their clinical characteristics and outcomes. Five molecular subtypes were resolved, termed MYD88, BCL2, SOCS1/SGK1, TET2/SGK1, and NOTCH2, along with an unclassified group. The subtypes characterized by genetic alterations of BCL2, NOTCH2, and MYD88 recapitulated recent studies showing good, intermediate, and poor prognosis, respectively. The SOCS1/SGK1 subtype showed biological overlap with primary mediastinal B-cell lymphoma and conferred excellent prognosis. Although not identified as a distinct cluster, NOTCH1 mutation was associated with poor prognosis. The impact of TP53 mutation varied with genomic subtypes, conferring no effect in the NOTCH2 subtype and poor prognosis in the MYD88 subtype. Our findings confirm the existence of molecular subtypes of DLBCL, providing evidence that genomic tests have prognostic significance in non-selected DLBCL patients. The identification of both good and poor risk subtypes in patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) clearly show the clinical value of the approach, confirming the need for a consensus classification.

First Dose of BNT162b2 mRNA Vaccine in a Healthcare Worker Cohort Is Associated With Reduced Symptomatic and Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

Over the first 2 months of 2021, vaccination coverage of staff at Hull Teaching Hospitals with BNT162b2 increased from 8.3% to 82.5% and was associated with a significant reduction in symptomatic and asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. The proportion of positive lateral flow tests from asymptomatic screening was maintained over this period.

Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real-world analysis of outcomes in 211 patients.

Ibrutinib is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and clinical trial data supports use at second line compared to later relapse. We aimed to investigate outcomes and tolerability for ibrutinib when given second line in a real-world setting. Our multicentre retrospective analysis included 211 R/R MCL patients, median age 73 years, receiving ibrutinib second-line within the United Kingdom's National Health Service. Overall response to ibrutinib was 69% (complete response 27%). The median progression-free survival (PFS) was 17·8 months (95% CI 13·1-22·2) and median overall survival (OS) 23·9 months (95% CI 15·0-32·8). Drug-related adverse event led to dose reduction in 10% of patients and discontinuation in 5%. In patients with progressive disease, accounting for 100 of 152 patients stopping ibrutinib, 43% received further systemic therapy. Post-ibrutinib rituximab, bendamustine and cytarabine (R-BAC) showed a trend toward improved survival compared to alternative systemic treatments (post-ibrutinib median OS 14·0 months, 95% CI 8·1-19·8, vs. 3·6 months, 95% CI 2·6-4·5, P = 0·06). Our study confirms the clinical benefit and good tolerability of ibrutinib at first relapse in a real-world population. Patients progressing on ibrutinib had limited survival but outcomes with R-BAC in select patients were promising.

Risk of mature B-cell neoplasms and precursor conditions after joint replacement: A report from the Haematological Malignancy Research Network.

Associations between previous joint replacement and B-cell lymphoid malignancies have been reported, but despite numerous reports, associations with the disease subtypes have received little attention. Using a UK-based register of haematological malignancies and a matched general population-based cohort, joint replacements from linked hospital inpatient records were examined. Cases diagnosed 2009-2015 who were aged 50 years or more were included; 8,013 mature B-cell neoplasms comprising myeloma (n = 1,763), diffuse large B-cell lymphoma (DLBCL, n = 1,676), chronic lymphocytic leukaemia (CLL, n = 1,594), marginal zone lymphoma (MZL, n = 957), follicular lymphoma (FL, n = 725) and classical Hodgkin lymphoma (CHL, n = 255), together with monoclonal gammopathy of uncertain significance (MGUS, n = 2,138) and monoclonal B-cell lymphocytosis (MBL, n = 632). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated relative to 10 age- and sex-matched controls using conditional logistic regression. Having had a joint replacement before diagnosis was associated with myeloma (OR = 1.3, 95% CI 1.1-1.5, p = 0.008) and MGUS (OR = 1.3, 95% CI 1.1-1.5, p < 0.001). Excluding replacements in the year before diagnosis, the MGUS risk remained, elevated where two or more joints were replaced (OR = 1.5, 95% CI 1.2-2.0, p = 0.001), with hip (OR = 1.2, 95% CI 1.0-1.5, p = 0.06) or knee replacements (OR = 1.5, 95% CI 1.2-1.8, p < 0.001). Associations with CHL and two or more replacements (OR = 2.7, 95% CI 1.3-5.6, p = 0.005) or hip replacements (OR = 1.9, 95% CI 1.0-3.4, p = 0.04); and between DLBCL and knee replacements (OR = 1.3, 95% CI 1.0-1.6, p = 0.04) were also observed. Our study reports for the first time a relationship between joint replacements and MGUS; while absolute risks of disease are low and not of major public health concern, these findings warrant further investigation.

The UK NCRI study of chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced stage follicular lymphoma: molecular response strongly predicts prolonged overall survival.

We present a long-term follow-up of the UK chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced, symptomatic follicular lymphoma (FL). This trial was the first to prospectively assess molecular response and the impact on outcomes for 400 patients. The median progression-free survival (PFS) and overall survival (OS) for CMD were 3·6 and 14·6 years vs. 3·0 and 15·7 years for FMD, respectively. Estimates for Restricted Mean Survival Time (RMST) suggested no difference in PFS or OS. For the whole cohort there was a highly significant difference in survival by POD24, with a median OS from a risk-defining event of 3·9 years compared to 13·7 years for all others (RMST P < 0·001). Molecular remission was achieved in 25/46 patients (54·3%) in the CMD arm and 20/41 (48·8%) in the FMD arm (P = 0·6). Molecular negativity resulted in median PFS of 5·6 years vs. 2·3 years for molecularly positive (log-rank P < 0·001) and median OS not reached versus 12·5 years (log-rank P < 0·01). No cases of progression occurred in minimal residual disease (MRD) negative patients after six years of follow-up. Although there was no difference in outcomes between arms, this is the first prospective study to report MRD negativity resulting in significantly improved OS.

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. 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.

Impact of novel therapies for mantle cell lymphoma in the real world setting: a report from the UK's Haematological Malignancy Research Network (HMRN).

The treatment landscape for mantle cell lymphoma (MCL) has changed dramatically in recent years, with findings from clinical trials reporting improvements in survival. Data on the general patient population are, however, sparse; and it is unclear whether the effects observed in clinical trials have translated into the real-world setting. To investigate this, we examined first-line and relapsed/refractory (RR) disease management in 335 MCL patients diagnosed between 2004 and 2015 in an established population-based patient cohort, along with data on demographic, diagnostic and prognostic factors. Marked treatment and survival changes were observed; first-line rituximab immunotherapy, for example, increased from 32% to 86% over the 11-year period, and median survival increased from 2·0 years among those first treated in 2004-2011 to 3·5 years among those treated in 2012-2015. Outcomes for RR disease also improved, from 8 months in 2004-2011 to 16·8 months in 2012-2015, coinciding with the introduction of agents, such as bendamustine and ibrutinib. Encouragingly, improvements were seen across all ages; 1-year overall survival among patients over 70 years treated for RR disease almost doubled. Our analyses underscore the importance of monitoring the impact of treatment changes in the real-world setting.

A Generic Model for Follicular Lymphoma: Predicting Cost, Life Expectancy, and Quality-Adjusted-Life-Year Using UK Population-Based Observational Data.

OBJECTIVES: To use real-world data to develop a flexible generic decision model to predict cost, life expectancy, and quality-adjusted life-years (QALYs) for follicular lymphoma (FL) in the general patient population. METHODS: All patients newly diagnosed with FL in the UK's population-based Haematological Malignancy Research Network (www.hmrn.org) between 2004 and 2011 were followed until 2015 (N = 740). Treatment pathways, QALYs, and costs were incorporated into a discrete event simulation to reflect patient heterogeneity, including age and disease management. Two scenario analyses, based on the latest National Institute for Health and Clinical Excellence (NICE) guidelines (rituximab induction therapy for newly diagnosed asymptomatic patients and rituximab maintenance therapy for patients between treatments), were conducted and their economic impacts were compared to current practice. RESULTS: Incidence-based analysis revealed expected average lifetime costs ranging from £6,165 [US$7,709] to £63,864 [US$79,862] per patient, and average life expectancy from 75 days to 17.56 years. Prevalence-based analysis estimated average annual treatment costs of £60-65 million [US$75-80 million], accounting for approximately 10% of the United Kingdom's annual National Health Service budget for hematological cancers as a whole. Assuming that treatment effects reported in trials are applicable to all patient groups, scenario analyses for two recent NICE guidelines demonstrated potential annual cost savings for the United Kingdom that ranged with uptake frequency from £0.6 million to £11 million [US$0.75-2.75 million]. CONCLUSIONS: Costs, survival, and QALYs associated with FL vary markedly with patient characteristics and disease management. Allowing the production of more realistic outcomes across the patient population as a whole, our model addresses this heterogeneity and is a useful tool with which to evaluate new technologies/treatments to support healthcare decision makers.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Multiple myeloma: routes to diagnosis, clinical characteristics and survival - findings from a UK population-based study.

Prompt cancer diagnosis may align UK survival with European averages. We examined the impact of route to diagnosis on survival for multiple myeloma patients diagnosed 2012-2013 using data from our population-based patient cohort that links to national death notifications and collects details on treatment and response (n = 441). Emergency presentation was associated with advanced disease and poorer outcomes, and was the commonest route to diagnosis (28·1%) followed by General Practitioner urgent (19·0%) and two-week wait (17·2%) referrals. CRAB (elevated Calcium, Renal failure, Anaemia, Bone lesions) distribution varied by route (P < 0·001), with patients with emergency presentations most likely to have ≥2 features and significantly worse survival (log-rank test χ2  = 13·8, P = 0·0002).

Long-term medical costs and life expectancy of acute myeloid leukemia: a probabilistic decision model.

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.

Lymphoid blood cancers, incidence and survival 2005-2023: A report from the UK's Haematological Malignancy Research Network.

BACKGROUND: Population-based information on cancer incidence and outcome are required to inform clinical practice and research; but contemporary data are lacking for many lymphoid cancer subtypes. METHODS: Set within a socio-demographically representative UK population of ∼4 million, data are from an established UK patient cohort (N = 22,414 diagnoses). Information on incidence (crude and age-standardised) and survival (overall and net) is presented for > 40 subtypes. RESULTS: The median diagnostic age was 69.9 years (interquartile range 59.1-78.3), but unlike many other cancers, lymphoid malignancies can be diagnosed at any age; different subtypes dominating at different ages. Males were more likely to be diagnosed than females (age-standardised sex rate ratio: 1.55 (95% Confidence Interval: 1.50,1.59)), and most subtypes had a male predominance, some more than three-fold (e.g. Burkitt lymphoma 3.26 (2.42, 4.40)). Five-year net survival estimates varied hugely, ranging from 97.4% (95% CI: 56.5, 99.9) in patients with hairy cell leukaemia to 31.6% (95% CI: 2.5, 69.8) in those with T-cell prolymphocytic leukaemia. No significant sex difference in survival were observed for the majority of diagnoses; one exception being classical Hodgkin lymphoma, where males had a higher mortality (Excess Mortality Ratio: 1.44 (95% CI: 1.11, 1.87)). An improvement in survival over time was observed for some, but not all, of the major diagnostic groups. CONCLUSIONS: Marked incidence and survival variations by subtype, sex and age confirm the heterogeneity of lymphoid neoplasms and highlight the importance of accurately characterising disease entities. Despite recent improvements, routine cancer registration of lymphoid neoplasms remains challenging and new issues continue to emerge; including the lack of an international consensus on classification and the recording of progressions and transformations. Furthermore, the increasing need for additional molecular and genomic information required for accurate classification is likely to impact negatively on the quality of cancer registration data, especially in low income countries.

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. 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). RESULTS: 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. CONCLUSIONS: 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.

Experiences and preferences for psychosocial support: a qualitative study exploring the views of patients with chronic haematological cancers.

OBJECTIVES: Patients with chronic haematological cancers are often treated on a relapsing-remitting pathway, which may extend for many years. Such diagnoses are associated with uncertainties that often cause anxiety and distress, meaning patients (and families) are susceptible to potentially prolonged emotional difficulties, across the cancer journey. Experiences and preferences regarding psychosocial needs and support over time are relatively unexplored, which this study aimed to address. SETTING AND DESIGN: Set within the UK's Haematological Malignancy Research Network (an ongoing population-based cohort that generates evidence to underpin improved clinical practice) a qualitative, exploratory study was conducted, using semistructured interviews. Reflexive thematic analysis was used to assess the interview data via an exploratory, inductive approach, underpinned by the research questions. PARTICIPANTS: Thirty-five patients were included with chronic lymphocytic leukaemia, follicular lymphoma, marginal zone lymphoma or myeloma; 10 of whom were interviewed alongside a relative. RESULTS: Five themes were identified from the data: (1) accessing support, (2) individual coping behaviour affecting support preferences, (3) divergent and fluctuating thoughts on patient support forums, (4) the role, influence and needs of family and friends and (5) other sources of support and outstanding needs. Findings suggest that patients' individual attitudes towards support varied over time. This also influenced whether support was perceived to be available, and if it was then used. CONCLUSION: This study highlighted the variation in preferences towards psychosocial support among patients with chronic haematological cancers. As patients can live for many years with significant emotional difficulties, they may benefit from frequent monitoring of their psychosocial well-being, as well as signposting to holistic support, if this is needed.

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'. METHODS: In-depth interviews with 35 patients (10 accompanied by relatives) with chronic lymphocytic leukaemia, follicular lymphoma, marginal zone lymphoma or myeloma. Data were analysed using descriptive qualitative techniques. RESULTS: Patient views of Watch and Wait ranged along a continuum, from immediate acceptance, to concern about treatment deferral. Significant ongoing anxiety and distress were described by some, due to the uncertain pathways associated with Watch and Wait. Infrequent contact with clinical staff was said to exacerbate this, as there was limited opportunity to ask questions and seek reassurance. Patients indicated that the impact of their malignancy could be underestimated by clinicians; possibly due to them comparing chronic and acute subtypes. Most patients lacked knowledge of blood cancers. Support from clinicians was considered greater among treated patients, possibly due to increased contact, and many drew on relatives for aid. Most patients were satisfied with their time-allocation with haematology staff, although experiences could be improved by greater access to clinical nurse specialists, counselling services, and community-based facilities. CONCLUSION: Experiences varied. Anxiety about unpredictable futures could be more distressing than any physical symptoms and have a greater impact on quality of life. Ongoing assessment could facilitate identification of difficulties, and is particularly important among individuals without supportive networks.

Chronic myeloid leukaemia: A qualitative interview study exploring disease impact from patient and practitioner perspectives.

PURPOSE: Improvements in chronic myeloid leukaemia treatment mean it is now relevant to examine the experiences of living with this cancer over a lifetime. This qualitative study aimed to investigate the impact of chronic myeloid leukaemia, from patient and healthcare practitioner perspectives. METHODS: The research was set within the UK's Haematological Malignancy Research Network; a population-based cohort of patients newly diagnosed with blood cancer, treated at one of fourteen hospitals. Purposive sampling led to interviews with seventeen patients and thirteen health care practitioners. Data were analysed using thematic analysis. RESULTS: Two analytical themes, "Significant impact of disease and treatment" and "Mediators of the impact of disease and treatment", and six sub-themes, were derived from patient interviews and supported with data from practitioners. Chronic myeloid leukaemia was described by patients as having significant widespread impact, which could be mediated by their knowledge, social support, and the quality of healthcare systems. Practitioners reflected patient accounts, but could underestimate the impact of this cancer. They generally viewed chronic myeloid leukaemia as less complex, severe and impactful than acute blood cancers; a message that reassured patients at diagnosis, but could later unintentionally contribute to difficulties discussing side effects and struggles to cope. CONCLUSION: Chronic myeloid leukaemia may significantly impact individuals, particularly as it is experienced over the lifetime. Greater understanding and discussion of the breadth and extent to which patients are affected, including potential mediators, could enhance clinical care.

Whole genome expression profiling based on paraffin embedded tissue can be used to classify diffuse large B-cell lymphoma and predict clinical outcome.

This study tested the validity of whole-genome expression profiling (GEP) using RNA from formalin-fixed, paraffin-embedded (FFPE) tissue to sub-classify Diffuse Large B-cell Lymphoma (DLBCL), in a population based cohort of 172 patients. GEP was performed using Illumina Whole Genome cDNA-mediated Annealing, Selection, extension & Ligation, and tumours were classified into germinal centre (GCB), activated B-cell (ABC) and Type-III subtypes. The method was highly reproducible and reliably classified cell lines of known phenotype. GCB and ABC subtypes were each characterized by unique gene expression signatures consistent with previously published data. A significant relationship between subtype and survival was observed, with ABC having the worst clinical outcome and in a multivariate survival model only age and GEP class remained significant. This effect was not seen when tumours were classified by immunohistochemistry. There was a significant association between age and subtype (mean ages ABC - 72·8 years, GC - 68·4 years, Type-III - 64·5 years). Older patients with ABC subtype were also over-represented in patients who died soon after diagnosis. The relationship between prognosis and subtype improved when only patients assigned to the three categories with the highest level of confidence were analysed. This study demonstrates that GEP-based classification of DLBCL can be applied to RNA extracted from routine FFPE samples and has potential for use in stratified medicine trials and clinical practice.