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Published data describing the efficacy and safety of autologous stem-cell transplantation (autoSCT) in post-transplant lymphoproliferative disorders (PTLD) is limited to case reports. This is a retrospective analysis of 21 patients reported to the EBMT registry who received an autoSCT for PTLD post solid organ transplant (SOT). Median age at autoSCT was 47 (range: 22–71) years. The commonest SOTs were kidney (48%) and liver (24%). Commonest histologies included DLBCL-type PTLD (14/21) and plasmacytoma-like PTLD (3/21). Patients received a median of two lines of therapy (range: 1–4) pre-autoSCT. ECOG performance status pre-autoSCT was 0 in 14% and 1 in 86%. Remission status pre-autoSCT was CR 47% and PR 38%. BEAM conditioning was used in 57% and high-dose melphalan in 10%. The median follow-up post-autoSCT was 64 months for alive patients. 3-year PFS was 62% [95% confidence interval (CI) 44–87%] and 3-year OS was 61% [95% CI:43–86]. There were 12 deaths, including four related to autoSCT. 100-day non-relapse-mortality (NRM) was 14% and 1-year NRM was 24%. This study suggests that autoSCT, although feasible and with potential therapeutic activity, is associated with a high NRM, primarily driven by infectious toxicity. A multi-disciplinary approach, expert microbiological input and stringent patient selection are required to optimise outcomes.

The approval of Bruton tyrosine kinase (BTK) inhibitors in patients with previously untreated chronic lymphocytic leukaemia (CLL) was based on trials which compared ibrutinib with alkylating agents in patients considered unfit for fludarabine, cyclophosphamide, and rituximab, the most effective chemoimmunotherapy in CLL. We aimed to assess whether ibrutinib and rituximab is superior to fludarabine, cyclophosphamide, and rituximab in terms of progression-free survival. This study is an interim analysis of FLAIR, which is an open-label, randomised, controlled, phase 3 trial in patients with previously untreated CLL done at 101 UK National Health Service hospitals. Eligible patients were between 18 and 75 years of age with a WHO performance status of 2 or less and disease status requiring treatment according to International Workshop on CLL criteria. Patients with greater than 20% of their CLL cells having the chromosome 17p deletion were excluded. Patients were randomly assigned (1:1) by means of minimisation (Binet stage, age, sex, and centre) with a random element in a web-based system to ibrutinib and rituximab (ibrutinib administered orally at 420 mg/day for up to 6 years; rituximab administered intravenously at 375 mg/m2 on day 1 of cycle 1 and at 500 mg/m2 on day 1 of cycles 2–6 of a 28-day cycle) or fludarabine, cyclophosphamide, and rituximab (fludarabine 24 mg/m2 per day orally on day 1–5, cyclophosphamide 150 mg/m2 per day orally on days 1–5; rituximab as above for up to 6 cycles). The primary endpoint was progression-free survival, analysed by intention to treat. Safety analysis was per protocol. This study is registered with ISRCTN, ISRCTN01844152, and EudraCT, 2013-001944-76, and recruiting is complete. Between Sept 19, 2014, and July 19, 2018, of 1924 patients assessed for eligibility, 771 were randomly assigned with median age 62 years (IQR 56–67), 565 (73%) were male, 206 (27%) were female and 507 (66%) had a WHO performance status of 0. 385 patients were assigned to fludarabine, cyclophosphamide, and rituximab and 386 patients to ibrutinib and rituximab. After a median follow-up of 53 months (IQR 41–61) and at prespecified interim analysis, median progression-free survival was not reached (NR) with ibrutinib and rituximab and was 67 months (95% CI 63–NR) with fludarabine, cyclophosphamide, and rituximab (hazard ratio 0·44 [95% CI 0·32–0·60]; p<0·0001). The most common grade 3 or 4 adverse event was leukopenia (203 [54%] patients in the fludarabine, cyclophosphamide, and rituximab group and 55 [14%] patients in the ibrutinib and rituximab group. Serious adverse events were reported in 205 (53%) of 384 patients receiving ibrutinib and rituximab compared with 203 (54%) of 378 patients receiving fludarabine, cyclophosphamide, and rituximab. Two deaths in the fludarabine, cyclophosphamide, and rituximab group and three deaths in the ibrutinib and rituximab group were deemed to be probably related to treatment. There were eight sudden unexplained or cardiac deaths in the ibrutinib and rituximab group and two in the fludarabine, cyclophosphamide, and rituximab group. Front line treatment with ibrutinib and rituximab significantly improved progression-free survival compared with fludarabine, cyclophosphamide, and rituximab but did not improve overall survival. A small number of sudden unexplained or cardiac deaths in the ibrutinib and rituximab group were observed largely among patients with existing hypertension or history of cardiac disorder. Cancer Research UK and Janssen.

Introduction Cavernous sinus syndrome is rare, characterised by ophthalmoplegia, orbital congestion plus proptosis, trigeminal sensory loss, and sympathetic disturbance (Horner's syndrome).1 In this case, an elderly man presented with painful left 6th and 3rd nerve palsies. Investigations revealed an aggressive lymphoma to be the cause. Although tumour is the most common cause of cavernous sinus syndrome 2, it is unusual for systemic lymphoma to present in this way without other systemic symptoms. Case description An 82 year old man presented with subacute progressive left painful ophthalmoplegia and ptosis which clinically was consistent with 3rd and 6th cranial nerve palsies. He was otherwise well. His presentation blood tests included a normal full blood count, renal and liver function, erythrocyte sedimentation rate and serum calcium level. CT head with contrast including angiographic and venographic sequences was reported normal. His symptoms were attributed to microvascular cause. He represented as his symptoms evolved, and MRI head revealed an enhancing left cavernous sinus mass. In retrospect, this abnormality was evident on his CT head scan performed two weeks previously. His serum LDH was now raised and his CT body scan showed diffuse lymphadenopathy. Biopsy of an axillary lymph node confirmed small lymphocytic lymphoma. However, it was felt that this was insufficiently aggressive to account for his intracranial lesion, and thus he underwent biopsy of the cavernous sinus mass. Histology confirmed the clinical suspicion of Richter's syndrome: a rare transformation of low–grade to high–grade non–Hodgkin lymphoma. He was treated with dexamethasone and radiotherapy. Discussion Our case proved to be due to a rare cause, but it illustrates the importance of reviewing “normal” imaging when there is a strong clinical suspicion of a structural abnormality. Cavernous syndrome can be the presentation of haematological malignancy or other metastatic disease. Figure 1 (Left): CT head with contrast Figure 2 (Right): MRI head with gadolinium.

Following the emergence in 2009 of the new pandemic H1N1 influenza virus, which contained gene segments from pig, bird and human influenza viruses, it was apparent that a better scientific understanding is required of influenza viruses to protect public and animal health. The latest scientific data on biological properties of the virus, transmissibility, host susceptibility and epidemiology has been evaluated in order to identify factors that could be monitored in animals and that would suggest a risk of emergence of a new pandemic influenza strains. Virological studies and animal models have highlighted the importance of individual virus proteins but virulence and transmissibility are polygenic effects and no single genetic marker can be reliably associated with increased pathogenicity or transmissibility. It was concluded that current monitoring of the influenza gene pool in humans has been able to provide an alert for the emergence of new human influenza strains of public health significance. In contrast, there is an incomplete view of the influenza virus strains circulating among pigs and birds at the global level. Interpretation of the origins and pandemic potential of influenza viruses do require knowledge of the influenza gene pools in both pigs and birds, as well as other animal species. It is recommended that there should be long term support for a passive monitoring network in pigs and birds in order to promote greater understanding of the evolution of influenza viruses at the global level. Maximum benefit can only be obtained by applying an integrated approach involving the medical and veterinary networks including development of harmonised tools and approaches, exchange of virus strains and sequence data and enhancing the coordination and dissemination of the findings from the human, swine and avian networks.