Cathy Burton

Central nervous system chemoprophylaxis in non-Hodgkin lymphoma: current practice in the UK

Central nervous system (CNS) involvement in non‐Hodgkin lymphoma (NHL) is a well‐recognised complication. There is no consensus regarding indications for prophylaxis or a standard CNS chemoprophylaxis regimen. Current UK practice was evaluated using a questionnaire. A total of 223 questionnaires were sent to clinicians who administered chemotherapy to patients with NHL; 158 (71%) evaluable questionnaires were returned. The overwhelming majority of respondents used prophylaxis in all cases of lymphoblastic lymphoma (97%) and Burkitt lymphoma (96%). Ninety‐six per cent of respondents required risk factors to be present before prophylaxis was initiated in cases of diffuse large B‐cell lymphoma. The commonest risk factor was site of involvement (paranasal sinus 88%, testicular 85%, orbital cavity 78%, bone marrow 65% and bone 28%). Other risk factors included stage IV, high International Prognostic Index score, >1 extranodal site and raised lactate dehydrogenase levels (34%, 21%, 16% and 10%). A total of 82% did not give prophylaxis in follicular lymphoma and 90% used intrathecal chemotherapy as their preferred method of prophylaxis. The most popular regimen was 12·5 mg methotrexate with each cycle of chemotherapy for six courses. Thirty‐nine per cent used systemic chemotherapy for CNS prophylaxis either alone (4%) or as an adjunct to intrathecal prophylaxis (35%). These variations in the indications and methods of prophylaxis indicate that this subject deserves further review.

Chlorambucil versus observation after anti-Helicobacter therapy in gastric MALT lymphomas: results of the international randomised LY03 trial

Gastric mucosa‐associated lymphoid tissue (MALT) lymphomas are uncommon tumours characterised by a tendency to remain localised for long periods. The aetiological association between MALT lymphomas and Helicobacter pylori is well established. The role of additional chemotherapy after H. pylori eradication in localised MALT lymphomas is unclear. The LY03 trial was designed to establish whether chlorambucil after treatment for H. pylori would help prevent recurrence. Patients were treated with antibiotics for H. pylori infection. Those with successful eradication of H. pylori and no evidence of progression of lymphoma were eligible for randomisation to chlorambucil or observation. Two hundred and thirty‐one patients were registered. Ninety‐seven percent patients had H. pylori eradicated after antibiotics and 59% achieved macroscopically normal gastric mucosa. One hundred and ten patients were randomised. With a median follow‐up of 58 months, six patients were dead and 17 had recurrent/progressive disease. The recurrence/progression rates at 5 years were 11% for chlorambucil, and 21% for observation with a difference of 10%, 95% confidence interval (CI) = −9% to 29%, P = 0·15. No difference was detected in recurrence/progression‐free survival [Hazard Ratio (HR) = 0·96, 95% CI = 0·41–2·2, P = 0·91] or overall survival (HR = 1·93, 95% CI = 0·39–9·58, P = 0·42). This is the first randomised trial to show there is no good evidence to support that additional single agent chemotherapy to anti‐H. pylori treatment contributes to prevent recurrence in localised gastric MALT lymphomas.

A phase III trial comparing CHOP to PMitCEBO with or without G-CSF in patients aged 60 plus with aggressive non-Hodgkin's lymphoma.

The management of older patients with aggressive non-Hodgkins lymphoma presents a challenge to the physician. Age is a poor prognostic indicator, due to reduced ability to tolerate and maintain dose-intensive chemotherapy. Generally, older patients demonstrate a lower response rate, reduced survival and increased toxicity, although the majority of large randomised trials exclude older patients. This randomised trial was conducted in patients 60 years or over to compare CHOP (cyclophosphamide 750 mg m−2, doxorubicin 50 mg m−2, vincristine 1.4 mg m−2, prednisolone 100 mg) with PMitCEBO (mitoxantrone 7 mg m−2, cyclophosphamide 300 mg m−2, etoposide 150 mg m−2, vincristine 1.4 mg m−2, bleomycin 10 mg m−2 and prednisolone 50 mg). Due to the myelosuppressive nature of these regimens, patients were also randomised to the addition of G-CSF. The formal results of this trial with long-term follow-up are now reported. Data were analysed to assess efficacy and toxicity. Overall response rate was 84% in the CHOP arm and 83% in the PMitCEBO arm, with overall response rates of 83% for the use of G-CSF and 84% for no G-CSF. At median 44 months follow-up, there was no significant difference in failure-free, progression-free or overall survival between the CHOP and PMitCEBO arms. At 3 years, the actuarial failure-free survival was 44% in CHOP recipients and 42% in PMitCEBO recipients and the 3-year actuarial overall survival was 46% and 45% respectively. There was no significant difference in the failure-free, progression-free or overall survival with the addition of G-CSF.

Hodgkin's lymphoma and infection: findings from a UK case–control study

Between 1998 and 2003, 214 people with Hodgkins lymphoma and 214 controls randomly selected from population registers in the north of England (after matching for age and sex) were recruited and their primary care medical records examined for details of clinical diagnoses due to infectious and non-infectious conditions in the preceding 15 years. In the year before diagnosis of Hodgkins lymphoma, almost all cases (99%) visited their general practitioner (GP) at least once. In comparison with controls, the excess was evident both for visits with an infection (odds ratio (OR)=2.1; 95% confidence interval (CI) 1.4–3.2) and for visits with non-infectious problems (OR=17.2; 95% CI 6.7–43.9). During the rest of the 15-year period prior to diagnosis, the proportion of people visiting their GP with a non-infectious condition did not differ between cases and controls. In contrast, compared to controls, there was an excess of cases visiting the GP with an infection, a finding that was evident for at least a decade prior to diagnosis and increased linearly with time (P=0.02). This excess was not due to a specific infection(s) and may reflect underlying immune abnormality. Alternatively, infection may cause B-cell proliferation from which a malignant clone may evolve.

Impact of age and socioeconomic status on treatment and survival from aggressive lymphoma: a UK population-based study of diffuse large B-cell lymphoma

Highlights • Age and performance status were predicative of treatment and survival.• Sixty percent of patients ≥75 yrs were treated with curative intent.• Performance status was more discriminatory of treatment and survival than age.• Socio-economic factors were not predictive of survival.• Clinical characteristics aide interpretation of socio-demographic treatment/outcome trends.

Emergency admission and survival from aggressive non-Hodgkin lymphoma : A report from the UK's population-based Haematological Malignancy Research Network

Background Non-Hodgkin lymphoma (NHL) is often diagnosed after emergency presentation, a route associated with poor survival and an indicator of diagnostic delay. Accounting for around half of all NHLs, diffuse large B-cell lymphoma (DLBCL) is of particular interest since although it is potentially curable with standardised chemotherapy it can be challenging to identify at an early stage in the primary care setting. Patients and methods Set within a socio-demographically representative United Kingdom population of around 4 million people, data are from an established patient cohort. This report includes all patients (≥18 years) diagnosed with DLBCL 2004–2011 (n = 1660). Emergency admissions were identified via linkage to Hospital Episode Statistics using standard methods, and survival was examined using proportional hazards regression. Results Two out of every five patients were diagnosed following an emergency admission, and this was associated with advanced disease and poor survival (p < 0.001). Among the 80% of patients treated with curative chemotherapy, survival discrepancies emerged at the point of diagnosis; the adjusted hazard ratio (emergency versus non-emergency) at one month being 4.0 (95% confidence interval 1.9–8.2). No lasting impact was evident in patients who survived for 12 months or more. Conclusion Emergency presentation impacts negatively on DLBCL survival; patients presenting via this route have significantly poorer outcomes than patients with similar clinical characteristics who present via other routes.

Results of a multicentre UK‐wide retrospective study evaluating the efficacy of brentuximab vedotin in relapsed, refractory classical Hodgkin lymphoma in the transplant naive setting

Relapsed or refractory classical Hodgkin lymphoma (cHL) is associated with a poor outcome when standard chemotherapy fails. Brentuximab vedotin (BV) is an anti‐CD30 monoclonal antibody‐drug conjugate licensed for use at relapse after autologous stem cell transplant (ASCT) or following two prior therapies in those unsuitable for ASCT. There are limited data assessing the ability of BV to enable curative SCT. We performed a UK‐wide retrospective study of 99 SCT‐naïve relapsed/refractory cHL. All had received 2 prior lines and were deemed fit for transplant but had an insufficient remission to proceed. The median age was 32 years. Most had nodular sclerosis subtype, Eastern Cooperative Oncology Group performance status 0–1 and advanced stage disease. The median progression‐free survival (PFS) was 5·6 months and median overall survival (OS) was 37·2 months. The overall response rate was 56% (29% complete response; 27% partial response). 61% reached SCT: 34% immediately post‐BV and 27% following an inadequate BV response but were salvaged and underwent deferred SCT. Patients consolidated with SCT had a superior PFS and OS to those not receiving SCT (P < 0·001). BV is an effective, non‐toxic bridge to immediate SCT in 34% and deferred SCT in 27%. 39% never reached SCT with a PFS of 3·0 months, demonstrating the unmet need to improve outcomes in those unsuitable for SCT post‐BV.

Lack of effectiveness of routine clinic and blood test-based follow-up for diffuse large B cell lymphoma

ESP6500, ExAC) and the predicted severity called by 3 independent programs (PolyPhen, SIFT, MutationTaster) (D: damaging, P: probably damaging, (B) benign). Table SII. List of amplicons used for Ion Torrent sequencing. Amplicons were designed using genome build hg19. Table SIII. List of amplicons used for custom sequencing on the MiSeq platform. Amplicons were designed using genome build hg19.

Prognostic significance and correlation to gene expression profile of EZH2 mutations in diffuse large B‐cell lymphoma (DLBL) in 2 large prospective studies

EZH2, a histone methyl transferase subunit of Polycomb repressor complex 2, is frequently mutated in DLBL. Inhibitors of EZH2 have demonstrated promising responses in early clinical trials. We examined the frequency of EZH2 mutation in 2 large prospective series of DLBL and correlated this to clinical outcomes in relation to other biological features.

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