Abstract:
: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. Patients received a median of four prior lines of therapy, 83% were relapsed and refractory, and 70% refractory to their last dexamethasone-containing regimen. Suppression of serum C-reactive protein levels, a surrogate marker of IL6 inhibition, was demonstrated. There were no responses to siltuximab but combination therapy yielded a partial (17%) + minimal (6%) response rate of 23%, with responses seen in dexamethasone-refractory disease. The median time to progression, progression-free survival and overall survival for combination therapy was 4.4, 3.7 and 20.4 months respectively. 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.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Voorhees PM,Manges RF,Sonneveld P,Jagannath S,Somlo G,Krishnan A,Lentzsch S,Frank RC,Zweegman S,Wijermans PW,Orlowski RZ,Kranenburg B,Hall B,Casneuf T,Qin X,van de Velde H,Xie H,Thomas SKdoi
10.1111/bjh.12266subject
Has Abstractpub_date
2013-05-01 00:00:00pages
357-66issue
3eissn
0007-1048issn
1365-2141journal_volume
161pub_type
杂志文章,多中心研究abstract::This study describes the effect of ferritin on lymphocyte function in vitro. Peripheral blood lymphocytes isolated from normal donors were incubated with purified human splenic ferritin, and the mitogenic effect of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and mixed lymphocyte reaction ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb01142.x
更新日期:1979-07-01 00:00:00
abstract::Primary non-engraftment or early rejection after transplantation of haematopoietic stem cells represent life-threatening complications of allogeneic stem cell transplantation. Management of early graft failure has been problematic, as the risk of fatal infectious complications increases with the time of pancytopenia a...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02359.x
更新日期:2000-11-01 00:00:00
abstract::The TH line was established by bringing tumour cells from a multiple myeloma patient into suspension culture and subsequently cloning them by limiting dilution. The cultured cells show marked heterogeneity; there are ultrastructural differences between small and large TH cells, particularly with respect to the rough e...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb04526.x
更新日期:1991-10-01 00:00:00
abstract::Besides circulating in normal plasma, von Willebrand factor (VWF) is also stored at relatively high concentration within the alpha-granules of platelets. This pool of platelet VWF exists distinct from plasma VWF, and is enriched in haemostatically-active high molecular weight multimers. Interestingly, the glycosylatio...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2009.08052.x
更新日期:2010-03-01 00:00:00
abstract::Leucocyte alkaline phosphatase (LAP) is a marker of post-mitotic granulocytes and its activity is reduced or absent in chronic myelogenous leukaemia (CML) granulocytes as a consequence of LAP messenger RNA (mRNA) deficiency. We provide evidence that along the granulocytic maturation in normal marrow, the acquisition o...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::Three certified reference materials for thromboplastins are available from the Community Bureau of Reference (BCR) of the European Commission for calibration of commercial thromboplastins used for control of oral anticoagulant therapy. The long-term stability of these reference materials has been monitored by two inde...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb04209.x
更新日期:1988-03-01 00:00:00
abstract::Cytogenetic abnormalities (CA), especially of chromosome 13, have been used to identify a subgroup of previously untreated multiple myeloma (MM) patients with very poor prognosis despite high-dose therapy (HDT). We examined the prognostic implications of CA in 1000 MM patients receiving melphalan-based tandem autotran...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04455.x
更新日期:2003-08-01 00:00:00
abstract::Diamond-Blackfan anaemia (DBA) is a constitutional pure red cell aplasia presenting in early childhood. In some patients, neutropenia and/or thrombocytopenia have also been observed during the course of the disease. We have followed 28 patients with steroid-refractory DBA for up to 13 years with serial peripheral bloo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.01796.x
更新日期:2000-01-01 00:00:00
abstract::A t(5;12)(q33;p13) translocation has been detected in two patients with myeloid disorder and eosinophilia. Six other patients with haematological disease with eosinophilia with similar translocation have been published previously. The existence of a new entity, a myeloproliferative disorder with eosinophilia and t(5;1...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.1994.tb05029.x
更新日期:1994-10-01 00:00:00
abstract::Laboratory screening for lupus anticoagulant (LA) has been shown to be suboptimal in several studies. Guidelines have recently been published by an expert group for the British Committee for Standards in Haematology, in an attempt to standardize and improve screening procedures. The value of using screening tests conf...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03821.x
更新日期:2002-11-01 00:00:00
abstract::Analysis of complementary RNA molecules of junctional regions of rearranged T-cell-receptor-gamma genes show a pattern of conformational polymorphisms which is specific for an individual lymphocytic clone. In a blinded study we analysed formalin-fixed, paraffin-embedded histological specimens from gastrointestinal lym...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb04732.x
更新日期:1994-02-01 00:00:00
abstract::The humanized CD52 monoclonal antibody Campath-1H was used as first-line therapy in nine patients with progressive chronic lymphocytic leukaemia (CLL). Intravenous (n = 5) or subcutaneous (n = 4) injections (up to 30 mg/inj.) were given three times a week for a maximum of 18 weeks. Three patients achieved a complete r...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2141.1996.450989.x
更新日期:1996-04-01 00:00:00
abstract::Glanzmann's thrombasthenia (GT) results from a qualitative or quantitative defect of GPIIb-IIIa complexes (integrin alphaIIbbeta3). the fibrinogen receptor on platelets. This integrin plays a critical role in platelet aggregation. In this report we describe the molecular abnormalities of a patient with clinical and la...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00852.x
更新日期:1998-09-01 00:00:00
abstract::The impact of age, ethnicity and socio-economic deprivation in the era of novel anti-myeloma agents is unclear. Using linked national data from New Zealand, we evaluated the incidence, prevalence and overall survival (OS) of individuals who were diagnosed with myeloma between 2004 and 2016. The crude incidence rate in...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.16238
更新日期:2020-03-01 00:00:00
abstract::Cooley's original description of beta-thalassaemia major included marked bone deformities as a characteristic feature. These were thought to be due to expansion of haemopoiesis attempting to compensate for the congenital anaemia. Regular blood transfusions from infancy prevents these skeletal problems. Nevertheless, s...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.01108.x
更新日期:1998-12-01 00:00:00
abstract::A retrospective analysis of CD20 expression following rituximab for B-cell non-Hodgkin's lymphoma demonstrated a significant change in immunophenotype in 6/25 (24%) patients with persistent bone marrow (BM) infiltration. In three out of six patients, the B cells were uniformly CD20-/CD79alpha+, consistent with frank l...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.03019.x
更新日期:2001-09-01 00:00:00
abstract::Five paediatric cases of haemophagocytic lymphohistiocytosis (HLH) which showed proliferation of granular atypical lymphocytoid cells in bone marrow are reported. All cases were girls aged 8 months to 4 years who had marked hepatosplenomegaly. Marker analysis on peripheral blood mononuclear cells revealed an increase ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.d01-2082.x
更新日期:1997-03-01 00:00:00
abstract::Phytosterolaemia (sitosterolaemia) is a recessively inherited metabolic condition in which the absorption of both cholesterol and plant-derived cholesterol-like molecules at the gut is unselective and unrestricted. In haematology, Mediterranean stomatocytosis or Mediterranean macrothrombocytopenia is a poorly understo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05599.x
更新日期:2005-07-01 00:00:00
abstract::The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats. Here we have investig...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00801.x
更新日期:1998-07-01 00:00:00
abstract::Despite the importance of adverse event (AE) reporting, AEs are under-reported on clinical trials. We hypothesized that electronic medical record (EMR) data can ascertain laboratory-based AEs more accurately than those ascertained manually. EMR data on 12 AEs for patients enrolled on two Children's Oncology Group (COG...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14538
更新日期:2017-04-01 00:00:00
abstract::210 patients, with a history of venous thrombosis, have undergone prothrombotic investigations. In nine cases a consistent deficiency of antithrombin was identified. In five there was a reduction in the plasma antigenic concentration of antithrombin and in a further four cases deficiency was due to the presence of a d...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb08584.x
更新日期:1991-03-01 00:00:00
abstract::Immuno-alkaline phosphatase staining (by the APAAP technique) has been used to identify promegakaryoblasts in cell smears from 10 cases of leukaemia (three acute leukaemia, seven blast transformations). In all cases promegakaryoblasts were labelled by at least two anti-platelet glycoprotein (gp) antibodies, the highes...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb06140.x
更新日期:1987-01-01 00:00:00
abstract::Six hundred and nineteen patients with de novo acute myeloid leukaemia, entered into the Medical Research Council's eighth trial of therapy have been studied. All patients were treated with the same remission induction regimen. Pretreatment variables comprising age, clinical status, haematological status and a detaile...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb02200.x
更新日期:1986-11-01 00:00:00
abstract::Three patients with probable congenital erythrocytosis were studied to determine the role of erythropoietin (ESF) in their disease. In addition, haemoglobin function was measured and ESF excretion determined in response to reduction in the haemoglobin concentration. In two cases ESF excretion was clearly elevated abov...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1980.tb01179.x
更新日期:1980-01-01 00:00:00
abstract::This retrospective analysis was conducted in 64 patients diagnosed with type I cryoglobulinaemia (CG) followed at two French centres. Median follow-up was 6·75 years. CG was IgG in 60% and IgM in 40% of all cases and was asymptomatic in 16 patients (25%). Cold-triggered ischaemic skin manifestations were observed in 3...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/bjh.13196
更新日期:2015-03-01 00:00:00
abstract::Using a reverse transcription-polymerase chain reaction (RT-PCR), we identified a patient with typical clinical features of chronic myelogenous leukaemia (CML) in the chronic phase who showed no amplification of the CML-type BCR/ABL transcript. RT-PCR with primers detecting the acute lymphoid leukaemia (ALL)-type tran...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.d01-2066.x
更新日期:1997-03-01 00:00:00
abstract::Cytogenetic deletions of the short arm of chromosome 12 are common recurring alterations found in a wide range of haematological neoplasias, including childhood acute lymphoblastic leukaemia (ALL), the most frequent paediatric malignancy. Such a loss of genetic material suggests the presence of a tumour suppressor gen...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.3663180.x
更新日期:1997-10-01 00:00:00
abstract::Umbilical cord blood is an alternative stem cell source for patients without matched family donors. In this study, we examined several parameters that have not been studied in detail -- radiation dose, cell dose, age of mice, and maternal and neonatal characteristics of the cord blood donor -- that affect engraftment ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02904.x
更新日期:2001-07-01 00:00:00
abstract::Median overall survival (OS) has improved for patients with newly diagnosed multiple myeloma (NDMM), but prognosis varies depending on baseline patient characteristics. Current models use data from selected clinical trial populations, which prevent application to patients in an unselected community setting that reflec...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.16139
更新日期:2019-12-01 00:00:00
abstract::The putative natural killer (NK) cell lymphomas/leukaemias are a group of recently characterized haematolymphoid malignancies sharing an immunophenotype of CD3/Leu4- CD3epsilon+ CD56+, and a genotype of germline T-cell receptor genes. They frequently present in extranodal sites and exhibit a highly aggressive clinical...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.3223139.x
更新日期:1997-09-01 00:00:00