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Registry for Radiation Workers, and combined cohort ofnuclear workers in United States future analysis of the registry, which will incorporate all registered cohorts and updated dose histories (in-National cluding internal doses) and have a longer follow up, Atomic homb survivors"0 Registry for Radiation American will provide a firmer basis for deriving risk estimates Whole cohort Doses <_500 mSv Workers workers* from low dose and low dose rate exposures. Cohort size 75 991 95 217 35 933 Person years 2 185 000 1 218 000 705 000 From its inception the registry has been guided by an Collective dose (man Sv) 18 000 3 198 1 140 a Range of doses 0-4 or more 0-0-5 0-0-5 or more 0-0-5 or more avisory committee of eminent epidemiologists. We are Excess relative risk per Sv grateful to themi for their guidance over many years, to Sir

SummaryBackgroundOutcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients.MethodsWe did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0–3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1–5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m2 on days 1, 8, and 15, cisplatin 100 mg/m2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1–5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18).FindingsBetween June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6–38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21–1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections.InterpretationThe number of patien...

Summary Data on older patients with primary central nervous system lymphoma (PCNSL) are scarce. Comorbidities and performance status frequently compromise outcomes in this group. Medical records for consecutive patients ≥65 years (n = 244) with PCNSL diagnosed 2012–2017 from 14 UK centres were retrospectively reviewed. Of these 192 patients received methotrexate (MTX)‐based treatment. Patients were categorised based on clinician's treatment choice into ‘palliative’ (n = 52), ‘less intensive: MTX ± rituximab ± alkylators’ (n = 74) and ‘intensive: MTX/cytarabine combinations’ (n = 118) groups. Complete remission (CR) rate, two‐year progression‐free survival (PFS) and overall survival (OS) rates were 49%, 11% and 24% for the less intensive and 69%, 40% and 50% for the intensive groups. Treatment‐related mortality (TRM) was 6·8% for MTX‐treated patients. Median MTX cumulative dose was 8·8 g/m2 (range 1·5–21) over a median of three cycles. Higher relative dose intensity of MTX (MTX‐RDI) was associated with improved PFS and OS in both groups adjusting for age, Eastern cooperative oncology group (ECOG) score and baseline parameters. Two‐year PFS and OS for patients receiving four or more induction cycles followed by consolidation (n = 36) were 65% and 70% respectively. Older patients completing MTX‐based induction and consolidation had clinical outcomes similar to those in younger cohorts. These retrospective data suggest that maximising MTX‐RDI and delivering consolidation in a subgroup of older patients may improve clinical outcomes.

resolution. Nevertheless, the integrated analysis of these multiple layers of nucleic acid information is still at its beginning. In this context it is important to recognize, that information encoded in nucleic acids is in many aspects "fluent": genomic information transits from DNA via epigenomic regulation and expression patterns of RNA to its ultimate function. Moreover, during tumor evolution the information at all these levels transits from the germline state via driving changes to complex aberration patterns. Additionally, the information transits from mother to daughter cells which in turn receive further information from environmental factors. Thus, "a" lymphoma is indeed an ecosystem with multiple interacting levels of informational dysregulation which unlikely is comprehensively described by targeted re-sequencing on DNA level or transcriptional profiling alone.Thanks to the interdisciplinary cooperation of clinicians, pathologists, geneticists and bionformaticians within the interdisciplinary Germanwide MMML-network we have profiled meanwhile more than 250 germinal-center B-cell derived by sequencing and more than 800 B-cell lymphomas by array-based means for genomic, expression and methylation changes. This lecture will give examples on the strategies aiming at integrating these complementary levels of nucleic-acid-based OMICs data as well as novel insights into the biology of lymphomas provided by such integrative analyses.

Introduction: Relapsed/refractory (R/R) follicular lymphoma (FL) remains a difficult-to-treat condition, with limited treatment options. New, tolerable treatments with unique mechanisms of action are needed, especially for high-risk patients whose disease progresses within 24 months of diagnosis (POD24). The epigenetic regulator EZH2 catalyzes the histone 3 lysine 27 trimethylation (H3K27m3) gene suppressive mark, which is essential for BCL6-driven germinal center (GC) formation. Conversely, a reduction in EZH2 catalytic activity is required for centroblast differentiation and initiation of the GC exit program. Activating mutations (MT) in EZH2, present in ~20% of FL patients, and enhanced H3K27me3 prevent GC exit, resulting in GC hyperplasia and lymphomagenesis. Tazemetostat, an investigational, selective, oral EZH2 inhibitor, has demonstrated durable, single-agent, antitumor activity in R/R FL patients with MT or wild-type (WT) EZH2. Herein, we report newly emerging interim efficacy and safety data from the MT and WT cohorts and the POD24 subgroup. Methods: This open-label, multicenter, phase 2 study (NCT01897571) evaluated tazemetostat 800 mg administered orally twice daily in patients with MT or WT EZH2 R/R FL (Grade 1-3b). Key inclusion criteria included age ≥18 years, Eastern Cooperative Oncology Group performance status of 0-2, ≥2 prior treatment regimens, and measurable disease per 2007 IWG-NHL criteria. The primary endpoint was objective response rate (complete response + partial response). Secondary endpoints included progression-free survival and safety. The POD24 subgroup was composed of patients experiencing disease progression or relapse within 24 months of diagnosis or the start of frontline treatment with immunochemotherapy. Results: As of June 7, 2019, interim data were available for 99 patients (MT EZH2, n=45 [POD24, n=17; 38%]; WT EZH2, n=54 [POD24, n=30; 56%]). Of the 33 patients in the MT cohort with an objective response, 15 (45%) had a response at ≥6 months, 7 (21%) at ≥12 months, and 4 (12%) at ≥16 months. Of the 18 patients in the WT cohort with an objective response, 15 (83%) had a response at ≥6 months, 9 (50%) at ≥12 months, and 6 (33%) at ≥16 months. Data from the MT cohort continue to mature, with 11 (24%) patients enrolled in the past year and 17 (38%) patients still on treatment. Updated data from the fully enrolled MT cohort, and sub-group analyses from both WT and MT cohort, will be presented. Interim efficacy data from the response-evaluable population and POD24 subgroup of the MT and WT cohorts are presented in Table 1. These results demonstrate the potent, antitumor activity of tazemetostat regardless of the prognostic category of patients. Treatment-related Grade ≥3 adverse events (AEs) were reported in 17% of all patients and 15% of patients in the POD24 subgroup. The most frequently reported AEs were similar across the total population and the POD24 subgroup and included thrombocytopenia (3%), anemia (2%), asthenia (2%), vomiting (1%), and fatigue (1%). Five percent of all patients discontinued treatment, and 9% had dose reductions due to treatment-related AEs. No treatment-related Grade 5 AE and deaths were reported. Conclusion: Tazemetostat was generally well tolerated, with a low incidence of treatment-related AEs. Tazemetostat demonstrated clinically meaningful, durable, single-agent activity across a spectrum of patients with FL, including the POD24 subgroup, and pronounced responses in patients with EZH2 activating mutations. Disclosures Morschhauser: BMS: Honoraria; Roche/Genentech: Consultancy; Servier: Consultancy; Janssen: Honoraria; Celgene: Honoraria; Gilead: Consultancy. Tilly:servier: Honoraria; merck: Honoraria; roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Gilead: Honoraria; BMS: Honoraria; Karyopharm: Consultancy; Roche: Consultancy; Celgene: Consultancy, Research Funding; Astra-Zeneca: Consultancy. Phillips:Bayer: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Seattle Genetics: Consultancy; Gilead: Consultancy; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding. Ribrag:Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Research Funding; ArgenX: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; AZ: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel, accommodations, and expenses ; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses . Campbell:Janssen: Honoraria, Research Funding, Speakers Bureau. Jurczak:Servier: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Takeda: Research Funding; Bayer: Research Funding; Celgene: Research Funding; Roche: Research Funding; Morphosys: Research Funding; TG Therapeutics: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celtrion: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Gilead: Research Funding; AstraZeneca/Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding. McKay:Epizyme: Consultancy, Honoraria. Opat:Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria. Radford:GSK: Equity Ownership; ADC Therapeutics: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; AstraZeneca: Equity Ownership, Research Funding; Novartis: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Whalen:Epizyme: Employment, Equity Ownership. Rajarethinam:Epizyme: Employment, Equity Ownership. Navia:Epizyme: Employment, Equity Ownership. Adib:Epizyme: Employment, Equity Ownership. Salles:Amgen: Honoraria, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Epizyme: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events.

Royal Free London NHS Trust, London, UK Keywords: Hodgkin lymphoma, Hodgkin disease, lymphocyte predominant Hodgkin lymphoma.The guideline group was selected to be representative of UKbased medical experts. Ovid MEDLINE, Ovid EMBASE and DYNAMED were searched systematically for publications in English from 1980 to 2014 using the key words Hodgkin disease, Hodgkin lymphoma and lymphocyte predominant Hodgkin lymphoma. References from relevant publications were also searched. Editorials, studies with <8 cases, letters and conference abstracts were excluded. The writing group produced the draft guideline, which was reviewed by the British Committee for Standards in Haematology (BCSH) Haemato-oncology Task Force. Further comments were invited from a sounding board of the British Society for Haematology (BSH) and patient representatives identified through the Lymphoma Association.

Aims-To determine a concentration of ferritin below which the possibility of iron deficiency should be considered in elderly patients. Methods-Consecutive new referrals to a geriatric unit (n = 472) were studied prospectively. Full blood count, ferritin, serum vitamin B12 and red cell folate were measured for all patients. A blood film was assessed independently by three haematologists for features of iron deficiency. For those with ferritin of 12-45 nglml, bone marrow aspirates were performed and examined for the presence of stainable iron. When possible, a trial of oral iron was given to those with ferritin of < 45 nglml and response was determined by remeasurement of full blood count and ferritin after a minimum of three weeks of treatment. Results-Bone marrow examination was performed in 32 patients with ferritin of 12-45 nglml, of whom 27 (84%) had absent stainable iron, suggesting that most elderly patients with ferritin in this range have iron deficiency. Compared with those with ferritin of 100-299 ng/ml, in whom iron stores were presumed to be normal, patients with ferritin of nglml had a significantly lower mean haemoglobin and mean red blood cell volume. Furthermore, patients with ferritin up to 75 ng/ml had a significantly higher mean red cell distribution width, and were more likely to have an iron deficient blood film. Conclusion-Iron deficient erythropoiesis can occur in elderly patients with ferritin up to 75 nglml. This is much higher than the lower limit of the "normal" range usually quoted for younger subjects; this difference should be taken into account when ferritin concentrations are interpreted in elderly patients. ( Clin Pathol 1993;46:857-860)