British journal of haematology
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Multicenter Study Observational Study
Prospective observational cohort study of the association between thromboelastometry, coagulation and platelet parameters and bleeding in patients with haematological malignancies- the ATHENA study.
Previous studies have shown that total platelet count (TPC) inadequately predicts bleeding in thrombocytopenic patients with haematological malignancies. This prospective cohort study evaluated whether rotational thromboelastometry (ROTEM), coagulation or other platelet parameters were more strongly associated with bleeding than TPC. Adults treated at two UK haematology centres for haematological malignancy were enrolled if they had thrombocytopenia (TPC ≤ 50 × 10(9) /l) at beginning of, or during treatment (International Standard Randomized Controlled Trial Number 81226121). ⋯ Only AIPN was associated with bleeding after adjustment of test results for TPC (Odds Ratio 0·52, 95% confidence interval 0·28-0·97; P = 0·038). In a predictive model, AIPN was superior to TPC for predicting bleeding. This study indicates that AIPN may be more clinically useful than TPC at predicting bleeding.
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Despite advancements in the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. ⋯ Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa-associated lymphatic tissue (MZL/MALT) was 33·3% and 42·9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation.
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Myelofibrosis (MF) is a Philadelphia chromosome-negative stem cell myeloproliferative neoplasm (MPN) associated with cytopenias, splenomegaly, constitutional symptoms, and poor prognosis. MF patients commonly express JAK2 V617F mutation and activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling. Agents targeting the JAK/STAT pathway have demonstrated efficacy in patients with MF. ⋯ One patient (3%) achieved an IWG-MRT response. Common adverse events were thrombocytopenia (71.4%) and diarrhoea (80.0%). Although molecular correlative analyses suggested that panobinostat inhibits key intracellular targets, limited clinical activity was observed because of poor tolerance.
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Raised tricuspid regurgitant velocity (TRV) occurs in approximately 30% of adults with sickle cell disease (SCD), and has been shown to be an independent risk factor for death. TRV was assessed in 164 SCD patients who were subsequently followed up for survival. Raised pulmonary pressures were defined as a TRV jet ≥2.5 m/s on echocardiography. ⋯ TRV was not an independent risk factor for death. We have confirmed the association between raised TRV and mortality in a UK SCD population whose disease severity appears to be less than that reported in previous studies. Further prospective studies are needed to more clearly characterize which patient factors modify survival in SCD patients with raised TRV.
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Multicenter Study
A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma.
Interleukin-6 (IL6) plays a central role in multiple myeloma pathogenesis and confers resistance to corticosteroid-induced apoptosis. We therefore evaluated the efficacy and safety of siltuximab, an anti-IL6 monoclonal antibody, alone and in combination with dexamethasone, for patients with relapsed or refractory multiple myeloma who had ≥ 2 prior lines of therapy, one of which had to be bortezomib-based. Fourteen initial patients received siltuximab alone, 10 of whom had dexamethasone added for suboptimal response; 39 subsequent patients were treated with concurrent siltuximab and dexamethasone. ⋯ Haematological toxicity was common but manageable. Infections occurred in 57% of combination-treated patients, including ≥ grade 3 infections in 18%. Further study of siltuximab in modern corticosteroid-containing myeloma regimens is warranted, with special attention to infection-related toxicity.