Abstract:
:Ibrutinib is associated with response rate of 90% and median progression-free survival (PFS) in excess of 5 years in Waldenström macroglobulinaemia (WM) patients. CXCR4 mutations are detected in 30-40% of patients with WM and associate with lower rates of response and shorter PFS to ibrutinib therapy. Both frameshift (CXCR4FS ) and nonsense (CXCR4NS ) CXCR4 mutations have been described. The impact of these mutations on outcomes to ibrutinib have not been evaluated in WM patients. We studied consecutive patients with a diagnosis of WM, on ibrutinib therapy, for the presence of CXCR4FS and CXCR4NS mutations and evaluated the differences in response and PFS between groups. Of 180 patients, 68 patients (38%) had CXCR4 mutations; 49 (27%) had CXCR4NS and 19 (11%) had CXCR4FS mutations. In multivariate models, patients with CXCR4NS had lower odds of major response (Odds ratio 0·25, 95% confidence interval [CI] 0·12-0·53; P < 0·001) and worse PFS (Hazard ratio 4·02, 95% CI 1·95-8·26; P < 0·001) than patients without CXCR4 mutations. CXCR4FS was not associated with worse major response or PFS rates than patients without CXCR4 mutations. Our results suggest different response and PFS rates to ibrutinib for WM patients with CXCR4NS and CXCR4FS , and advocate in favour of CXCR4 mutational testing as well as CXCR4-directed therapy.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Castillo JJ,Xu L,Gustine JN,Keezer A,Meid K,Dubeau TE,Liu X,Demos MG,Kofides A,Tsakmaklis N,Chen JG,Munshi M,Guerrera ML,Chan GG,Patterson CJ,Yang G,Hunter ZR,Treon SPdoi
10.1111/bjh.16088subject
Has Abstractpub_date
2019-11-01 00:00:00pages
356-363issue
3eissn
0007-1048issn
1365-2141journal_volume
187pub_type
杂志文章abstract::Twenty-seven stable subclones of seven independent cellular hybrids producing murine monoclonal antibodies to human von Willebrand factor (vWF) have been established. The specificity of the hybridoma antibodies for vWF has been substantiated by a variety of methods including binding to highly purified vWF, absence of ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1984.tb02937.x
更新日期:1984-08-01 00:00:00
abstract::Fanconi anaemia (FA) is an autosomal recessive and X-linked disease characterized by severe genetic instability and increased incidence of cancer. One explanation for this instability may be the cellular hypersensitivity to oxidative stress leading to chromosomal breaks. This study explored the possible oxidative dama...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2008.07137.x
更新日期:2008-07-01 00:00:00
abstract::Survival outcome of patients with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) who experience disease progression/relapse remains very poor. A total of 321 patients, newly diagnosed with PTCL-NOS (n = 180) or AITL (n = 141) between 1999 and 2015, were anal...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14477
更新日期:2017-03-01 00:00:00
abstract::Clinical management of chronic lymphocytic leukaemia (CLL) in patients aged ≥80 years is based on limited evidence due to the lack of published information. Therefore, we analysed CLL patients aged ≥80 years using data from seven phase III clinical trials of the German CLL Study Group. Among 3552 participants, 152 wer...
journal_title:British journal of haematology
pub_type: 杂志文章,meta分析
doi:10.1111/bjh.15604
更新日期:2018-12-01 00:00:00
abstract::The EPB3 gene encodes band 3 (anion exchanger 1) of the red cell membrane. A subset of hereditary spherocytosis (HS) is associated with EPB3 gene mutations and band 3 deficiency. We report a large Italian family in which 10 of the 27 members investigated displayed an autosomal dominant HS. SDS-PAGE revealed a reductio...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.1983013.x
更新日期:1997-08-01 00:00:00
abstract::When stimulated in vitro, human platelets release matrix metalloproteinase-2 (MMP-2) that, in turn, potentiates platelet activation. The present study investigated if MMP-2 is released from activated platelets in vivo in humans and whether aspirin inhibits this release. MMP-2 levels were measured by zymography, immuno...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06632.x
更新日期:2007-07-01 00:00:00
abstract::Prior studies indicate that neutrophil extracellular traps (NETs) are associated with arterial thromboembolism (ATE) and mortality. We investigated the association between NET formation biomarkers (citrullinated histone H3 [H3Cit], cell-free DNA [cfDNA], and nucleosomes) and the risk of ATE and all-cause mortality in ...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/bjh.15906
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abstract::The significance of paroxysmal nocturnal haemoglobinuria (PNH(pos) ) cells and leucocyte subset telomere lengths in paediatric aplastic anaemia (AA) is unknown. Among 22 children receiving immunosuppressive therapy (IST) for AA, 73% (16/22) were PNH(pos) , of whom 94% achieved at least a partial response (PR) to IST; ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12656
更新日期:2014-03-01 00:00:00
abstract::The influence of erythrocyte shape changes on the sedimentation rate was studied in vitro and in vivo. In vitro the highest sedimentation rate was observed with a slight degree of stomatocytosis (morphological index-0.3; i.e. one red cell out of three being a stomatocyte I). With increasing degrees of stomatocytosis t...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb00296.x
更新日期:1989-12-01 00:00:00
abstract::Accumulating evidence indicates that a graft-vs.-myeloma effect (GVM) and its associated clinical remission of the disease can be induced by donor lymphocyte infusion in myeloma patients who have relapsed after allogeneic bone marrow transplantation. Although it is believed that GVM is induced by allospecific T cells,...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02531.x
更新日期:2001-02-01 00:00:00
abstract::Salivary gland mucosa-associated lymphoid tissue (MALT) lymphomas (SGML) are rare, as are data concerning their behaviour. We analysed clinical features at presentation, particularly the association with Sjoegren syndrome (SS) and hepatitis C virus (HCV) infection, and outcome in 33 cases of SGML diagnosed between Mar...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.04993.x
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abstract::T cells modified with anti-CD19 chimeric antigen receptor (CAR) containing either CD28 or 4-1BB (also termed TNFRSF9, CD137) costimulatory signalling have shown great potential in the treatment of acute lymphoblastic leukaemia (ALL). However, the difference between CD28 and 4-1BB costimulatory signalling in CAR-T trea...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.15195
更新日期:2018-05-01 00:00:00
abstract::Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL) is one of the more common forms of B cell malignancy. Although the condition has a variable clinical course, the trend is towards eventual relapse and the disease is considered incurable. Whilst the majority of the circulating CD5-positive neoplastic B cel...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.12344
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abstract::Human intravenous immunoglobulin (IVIg) and anti-D immunoglobulin preparations are used in the treatment of immune thrombocytopenic purpura (ITP). One mechanism proposed to explain their therapeutic effects in ITP patients is the induction of expression of anti-inflammatory cytokines, such as interleukin (IL)-10 or IL...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06495.x
更新日期:2007-03-01 00:00:00
abstract::Clonal T cells that cause pure red cell aplasia were demonstrated in a patient with chronic B-cell lymphocytic leukaemia. The T-cell fraction was enriched by the immunomagnetic method and shown to have T-cell receptor-beta gene rearrangement. Cryopreserved T cells, obtained during the period of anaemia, suppressed aut...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00711.x
更新日期:1998-05-01 00:00:00
abstract::Autologous or allogeneic peripheral blood T cells can stimulate the human megakaryocyte progenitor cell (CFU-Meg)-derived colony formation in a dose-dependent fashion in agar cultures of nonadherent (NA), T cell-depleted (NT) bone marrow (BM) cells. Low concentrations of monocytes and T cells can collaborate in the st...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1990.tb07830.x
更新日期:1990-09-01 00:00:00
abstract::The following diagnostic criteria are proposed to classify four clinical subtypes of HTLV-1 associated adult T-cell leukaemia-lymphoma (ATL): (1) Smouldering type, 5% or more abnormal lymphocytes of T-cell nature in PB, normal lymphocyte level (less than 4 x 10(9)/l), no hypercalcaemia (corrected calcium level less th...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb08051.x
更新日期:1991-11-01 00:00:00
abstract::The dependence of survival time on a set of prognostic factors was explored by means of Cox's regression model in 137 cases of myelofibrosis with myeloid metaplasia (MMM). The following parameters recorded at diagnosis proved to be important independent indicators of a poor prognosis: a higher value for age, a lower v...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02507.x
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abstract::Murine monoclonal antibodies (MoAbs) were produced against the blood group KEL1 glycoprotein (93 kD component) immunopurified from human erythrocytes. One monoclonal antibody, 5A11 (IgGa, kappa), detects by immunoblotting a 93 and 184 kD component from KEL: 1,-2 or KEL: -1,2 red cell membrane preparations, separated b...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb04539.x
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abstract::Non-haemolytic transfusion reactions are the most common type of transfusion reaction and include transfusion-related acute lung injury, transfusion-associated circulatory overload, allergic reactions, febrile reactions, post-transfusion purpura and graft-versus- host disease. Although life-threatening anaphylaxis occ...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
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abstract::This study was designed to determine the incidence of relapse and factors predictive for relapse in 719 patients with severe aplastic anaemia (SAA) after immunosuppressive treatment (IS). Patients developing myelodysplasia or acute leukaemia after IS, and patients receiving a transplant, were excluded from this analys...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb03181.x
更新日期:1993-10-01 00:00:00
abstract::In type 1 Gaucher disease a bleeding tendency occurs which is partly caused by thrombocytopenia due to massive splenomegaly. In addition, low levels of factors IX and XI have been described. The mechanism responsible for these clotting factor abnormalities is unknown. We performed a detailed study of parameters of coa...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.d01-2076.x
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abstract::The object of this study was to determine whether there were any differences between the 'typical' child with fever and neutropenia and their adult counterpart with regard to infection type and outcome, by analysis of 3080 patients, including 759 children < 18 years of age and 2321 adults. These represented patients r...
journal_title:British journal of haematology
pub_type: 杂志文章,meta分析
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更新日期:1997-12-01 00:00:00
abstract::In a patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL), a novel variant of the chimaeric BCR-ABL mRNA transcript was detected by reverse transcription polymerase chain reaction (RT-PCR). Sequencing revealed the novel transcript to be a chimaeric mRNA produced by fusion of the BCR exon 1...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02205.x
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abstract::Myeloperoxidase (MPO) catalyses the formation of hypochlorous acid and is involved in many (patho)physiological processes. The present study was designed to determine the effect of two MPO promoter polymorphisms (463G/A and 129G/A) on enzyme activity. In 243 healthy controls, genotypes were determined and MPO activity...
journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.13795
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abstract::The regulatory human immunodeficiency virus-1 (HIV-1) Tat protein shows pleiotropic effects on the survival and growth of both HIV-1-infected and uninfected CD4+ T lymphocytes. In this study, we have demonstrated that low concentrations (10 ng/ml) of extracellular Tat protein induce the expression of both c-fos mRNA a...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02576.x
更新日期:2001-03-01 00:00:00
abstract::Sixty years ago there was little interest in venous thromboembolism (VTE) in global medical circles, and the British were no different in this respect. And yet, from nowhere the clinical field has developed: now prevention and management of VTE accounts for a large part of many consultant haematologists' working life,...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.17152
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abstract::End-stage renal failure (ESRF) patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are immunocompromised and exhibit abnormal circulating polymorphonuclear leucocyte (PMN) function, including reduced phagocytosis and intracellular killing. Six uraemic patients on CAPD were each given 300 microg granul...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.01019.x
更新日期:1998-11-01 00:00:00
abstract::SAn ageing population and the continuing expansion of clinical indications for coumadin therapy have increased pressure on hospital anticoagulant clinics. One solution is patient self-testing (PST) of the international normalized ratio (INR) using capillary blood samples on point-of-care coagulation monitors at home. ...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2141.2004.05300.x
更新日期:2005-01-01 00:00:00