Abstract:
:Chronic lymphocytic leukemia is an incurable B-cell malignancy that is associated with tumor cell-mediated T-cell dysfunction. It therefore represents a challenging disease for T-cell immunotherapeutics. The CD19/CD3 bi-specific antibody construct blinatumomab (AMG103 or MT103) has been tested clinically in non-Hodgkin's lymphoma and acute lymphoblastic leukemia but has not been assessed in chronic lymphocytic leukemia. We investigated whether blinatumomab could overcome T-cell dysfunction in chronic lymphocytic leukemia in vitro. Blinatumomab was tested on peripheral blood mononuclear cells from 28 patients (treatment naïve and previously treated). T-cell activation and function, as well as cytotoxicity against leukemic tumor cells were measured. Blinatumomab induced T-cell activation, proliferation, cytokine secretion and granzyme B release in a manner similar to that occurring with stimulation with anti-CD3/anti-CD28 beads. However, only blinatumomab was able to induce tumor cell death and this was found to require blinatumomab-mediated conjugate formation between T cells and tumor cells. Cytotoxicity of tumor cells was observed at very low T-cell:tumor cell ratios. A three-dimensional model based on confocal microscopy suggested that up to 11 tumor cells could cluster round each T cell. Importantly, blinatumomab induced cytotoxicity against tumor cells in samples from both treatment-naïve and treated patients, and in the presence of co-culture pro-survival signals. The potent cytotoxic action of blinatumomab on tumor cells appears to involve conjugation of T cells with tumor cells at both the activation and effector stages. The efficacy of blinatumomab in vitro suggests that the bi-specific antibody approach may be a powerful immunotherapeutic strategy in chronic lymphocytic leukemia.
journal_name
Haematologicajournal_title
Haematologicaauthors
Wong R,Pepper C,Brennan P,Nagorsen D,Man S,Fegan Cdoi
10.3324/haematol.2012.082248subject
Has Abstractpub_date
2013-12-01 00:00:00pages
1930-8issue
12eissn
0390-6078issn
1592-8721pii
haematol.2012.082248journal_volume
98pub_type
杂志文章相关文献
HAEMATOLOGICA文献大全abstract::Activation of the phosphatidylinositol 3-kinase/mechanistic target of rapamycin pathway plays a role in the pathogenesis of non-Hodgkin lymphoma. This multicenter, open-label phase 2 study evaluated buparlisib (BKM120), a pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or refractory non-...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:10.3324/haematol.2017.169656
更新日期:2017-12-01 00:00:00
abstract:BACKGROUND:We previously described a t(2;11)(p21;q23) chromosomal translocation found in patients with myelodysplasia or acute myeloid leukemia that leads to over-expression of the microRNA miR-125b, and we showed that transplantation of mice with murine stem/progenitor cells overexpressing miR-125b is able to induce l...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2011.061515
更新日期:2012-11-01 00:00:00
abstract::Daily intravenous arsenic trioxide administered with all-trans retinoid acid, the standard-of-care for acute promyelocytic leukemia, is costly and challenging to administer. ORH-2014 is a novel, oral arsenic trioxide formulation, consisting of micron-size drug particles with rapid dissolution and high bioavailability....
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2019.229583
更新日期:2020-06-01 00:00:00
abstract::With the deaths of Janet Rowley and John Goldman in December 2013, the world lost two pioneers in the field of chronic myeloid leukemia. In 1973, Janet Rowley, unraveled the cytogenetic anatomy of the Philadelphia chromosome, which subsequently led to the identification of the BCR-ABL1 fusion gene and its principal pa...
journal_title:Haematologica
pub_type: 传,历史文章,杂志文章,评审
doi:10.3324/haematol.2015.139337
更新日期:2016-05-01 00:00:00
abstract::We quantified Wilm's tumor gene (WT1) using a real time quantitative polymerase chain reaction in 20 adult patients with acute lymphoblastic leukemia at presentation. A WT1 level greater than 906 (median value for the whole series) was a significant predictor of a poor disease-free and overall survival in uni- and mul...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Relapsing primary central nervous system lymphoma carries a poor prognosis when treated with conventional chemotherapy with a one-year overall survival of 25-40%. Encouraging results have been shown with intensive chemotherapy followed by autologous hematopoietic stem cell rescue. We report the results of a ...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:10.3324/haematol.2011.060434
更新日期:2012-11-01 00:00:00
abstract::In contrast to well-established hierarchical concepts of tumor stem cells, leukemia-initiating cells in B-cell precursor acute lymphoblastic leukemia have not yet been phenotypically identified. Different subpopulations, as defined by surface markers, have shown equal abilities to reconstitute leukemia upon transplant...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2017.167502
更新日期:2018-06-01 00:00:00
abstract::Monitoring minimal residual disease is an important way to identify patients with acute myeloid leukemia at high risk of relapse. In this study we investigated the prognostic potential of minimal residual disease monitoring by quantitative real-time polymerase chain reaction analysis of NPM1 mutations in patients trea...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:10.3324/haematol.2014.104133
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:With the development and refinement of guidance modalities for percutaneous biopsies, many investigators have reported studies supporting the role of guided core needle biopsy in the diagnosis of mediastinal lymphoma. The aims of this report are to evaluate the efficacy of findings at core need...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:This study was designed to evaluate the efficacy and toxicity of monthly alternating ABVD/MOPP compared to ABVD/OPP regimens in patients with advanced stage Hodgkin's disease (HD), as well as in early stage patients with systemic symptoms and/or bulky disease. DESIGN AND METHODS:218 patients w...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1998-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:In March 1987 AIEOP started the AIEOP-ALL-87 study, based on the previous AIEOP-ALL-82. The aim of this new study was to evaluate, for all risk groups: a) the efficacy of treatment intensification achieved by adding a fourth drug (daunomycin) in the induction phase and a 3-drug reinduction pha...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The detection of PML-RARalpha by real-time polymerase chain reaction (RQ-PCR) is becoming an important tool for monitoring minimal residual disease (MRD) in patients with acute promyelocytic leukemia (APL). However, its clinical value remains to be determined. Our aim was to analyze any associ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10734
更新日期:2007-03-01 00:00:00
abstract::The main purpose of this work is to give methodologic details and further verification regarding the predictive system recently elaborated for Hodgkin's disease (HD) patients, by which, under standard accuracy and conventional treatment, patient survival can be directly estimated (within a given confidence interval) w...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::BCL11A was the focus of recent studies on its inhibiting effect when bound onto the β-globin cluster in the mechanism of hemoglobin switching and HbF downregulation. We examined a cohort of 10 patients displaying different HbF levels and short deletions within the γβ-δ intergenic region to find a possible correlation ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2012.061994
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:We analyzed the factors that affected the number and quality of peripheral blood stem cells (PBSC) collected for transplant in order to establish a minimum threshold for rapid hematopoietic recovery. DESIGN AND METHODS:From January 1995 to November 1996, a consecutive series of 67 patients, wi...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::The regulation of platelets by oxidants is critical for vascular health and may explain thrombotic complications in diseases such as diabetes and dementia, but remains poorly understood. Here, we describe a novel technique combining electron paramagnetic resonance spectroscopy and turbidimetry, which has been utilized...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.208819
更新日期:2019-09-01 00:00:00
abstract::We conducted a phase I/II multicenter trial using 6 cycles of brentuximab vedotin (BV) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for treatment of patients with CD30-positive (+) B-cell lymphomas. Thirty-one patients were evaluable for toxicity and 29 for efficacy including 22...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2019.238675
更新日期:2020-05-15 00:00:00
abstract::In childhood B-cell precursor acute lymphoblastic leukemia, cytogenetics is important in diagnosis and as an indicator of response to therapy, thus playing a key role in risk stratification of patients for treatment. Little is known of the relationship between different cytogenetic subtypes in B-cell precursor acute l...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,多中心研究
doi:10.3324/haematol.2013.085175
更新日期:2013-07-01 00:00:00
abstract::We studied the impact of comorbidities on survival and evaluated the prognostic utility of comorbidity scores in MDS patients, who received best supportive care and were assessable according to the Charlson Comorbidity Index (CCI) and the Hematopoietic Stem Cell Transplantation Comorbidity Index (HCTCI): 171 patients ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2008.002063
更新日期:2009-05-01 00:00:00
abstract::B-cell chronic lymphocytic leukemia-related genomic changes were analyzed by karyotyping, fluorescence in situ hybridization, and V(H) gene sequencing in a prospective clinical evaluation. The V(H) mutational status correlated with high-risk cytogenetic aberrations while no such relation could be demonstrated for spec...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND:Transcription factors play essential roles in both normal and malignant hematopoiesis. This is the case for the growth factor independent 1b (GFI1B) transcription factor, which is required for erythroid and megakaryocytic differentiation and over-expressed in leukemic patients and cell lines. DESIGN AND MET...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2009.012351
更新日期:2010-01-01 00:00:00
abstract::Here we critically evaluate the role of elevated hematocrit as the principal determinant of thrombotic risk in polycythemia and erythrocytosis, defined by an expansion of red cell mass. Since red cell volume determination is no longer readily available, in clinical practice, polycythemia and erythrocytosis are defined...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:10.3324/haematol.2018.210732
更新日期:2019-04-01 00:00:00
abstract::Macaques are emerging as a critical animal model in transfusion medicine, because of their evolutionary similarity to humans and perceived utility in discovery and translational science. However, little is known about the metabolism of Rhesus macaque red blood cells (RBC) and how this compares to human RBC metabolism ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2019.229930
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The differential diagnosis between multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) may be uncertain in some cases; this problem is reflected by discrepancies between different classification systems with an accordance in only 2/3 of cases. We studied whether...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2001-08-01 00:00:00
abstract::Seven cord blood (CB) units were tested for their capacity to repopulate irradiated NOD/SCID mice after one or two successive cryopreservation procedures. In primary transplants with frozen or refrozen CB cells we observed equivalent human colonies and percentages of human CD45+ cells, with multilineage engraftment. I...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2006-03-01 00:00:00
abstract:BACKGROUND:Chronic lymphocytic leukemia is a neoplastic disorder that arises largely as a result of defective apoptosis leading to chemoresistance. Stromal cell-derived factor-1 and its receptor, CXCR4, have been shown to play an important role in chronic lymphocytic leukemia cell trafficking and survival. DESIGN AND ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2009.013847
更新日期:2010-07-01 00:00:00
abstract::Juvenile hemochromatosis is a severe form of hereditary iron overload. It can be caused by mutations in either hepcidin or hemojuvelin genes. In this study we identified the molecular basis of juvenile hemochromatosis in three Australian families and assessed the role of potential modifying genes in individuals carryi...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2005-02-01 00:00:00
abstract:OBJECTIVES:Perceiving the need for rigorous recommendations to facilitate decisions concerning the management of patients with multiple myeloma (MM), the Italian Society of Hematology (SIE) and the two affiliate societies (SIES and GITMO) commissioned a project to develop guidelines for the therapy of MM using evidence...
journal_title:Haematologica
pub_type: 杂志文章,实务指引,评审
doi:
更新日期:2004-06-01 00:00:00
abstract::Iron recycling by macrophages is essential for erythropoiesis, but may also be relevant for iron redistribution to neighboring cells at the local tissue level. Using mice with iron retention in macrophages due to targeted inactivation of the iron exporter ferroportin, we investigated the role of macrophage iron releas...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.197517
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The rate of post-operative asymptomatic deep-vein thrombosis in Asian patients remains uncertain. The aim of this study was to estimate the rate of venous thromboembolism, including asymptomatic deep-vein thrombosis, undergoing hip or knee surgery and not receiving pharmacological thromboproph...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.10819
更新日期:2007-09-01 00:00:00