Abstract:
OBJECTIVES:To investigate whether the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) combined with the selective MDM2 antagonist idasanutlin (RG7388) offers superior efficacy to monotherapy in treating B-lymphoid malignancies in preclinical models. METHODS:The combined effect of obinutuzumab or rituximab plus idasanutlin on direct cell death/apoptosis induction and antibody-dependent cellular cytotoxicity (ADCC) was evaluated using p53 wild-type Z-138 and DoHH-2 lymphoma cells. Furthermore, whole blood B-cell depletion was analysed, and tumour growth inhibition was evaluated in subcutaneous xenograft models. RESULTS:Idasanutlin induced concentration-dependent death of Z-138 and DoHH-2 cells. At concentrations >10-100 nm, idasanutlin enhanced obinutuzumab-induced death of DoHH-2 and Z-138 cells without negatively impacting obinutuzumab-mediated ADCC, natural killer cell activation or whole blood B-cell depletion. In the Z-138 xenograft model, a suboptimal dose of obinutuzumab with idasanutlin yielded substantial tumour growth inhibition and prolonged survival in a time-to-event analysis. In the DoHH-2 model, idasanutlin plus obinutuzumab showed superior tumour growth inhibition to idasanutlin plus rituximab. CONCLUSIONS:Obinutuzumab plus idasanutlin enhanced cell death of p53 wild-type tumour cells vs. rituximab plus idasanutlin without affecting obinutuzumab-mediated ADCC or B-cell depletion and showed robust antitumour efficacy in xenograft models, strongly supporting the investigation of this combination in clinical trials.
journal_name
Eur J Haematoljournal_title
European journal of haematologyauthors
Herting F,Herter S,Friess T,Muth G,Bacac M,Sulcova J,Umana P,Dangl M,Klein Cdoi
10.1111/ejh.12756subject
Has Abstractpub_date
2016-11-01 00:00:00pages
461-470issue
5eissn
0902-4441issn
1600-0609journal_volume
97pub_type
杂志文章abstract::A murine cultured cell line (MKM-O) was established from a tumor of a BALB/C (nu/nu) mouse that had been subcutaneously inoculated with human hepatoma tissue fragments in the same location. The MKM-O cell line was proven to be of endothelial origin by morphological examinations and positive staining with fluorescein-l...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1987.tb00743.x
更新日期:1987-08-01 00:00:00
abstract::Alkaline phosphatase (ALP) activity of 70 cases of non-Hodgkin's lymphomas of the B-cell type was studied. ALP activity was found in malignant lymphoma (ML), follicular, small cleaved cell (1/5 cases); ML, diffuse, small cleaved cell (3/13 cases); and mantle zone lymphoma (intermediate lymphocytic lymphoma) (2/2 cases...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1988.tb01185.x
更新日期:1988-09-01 00:00:00
abstract::Sickle cell disease (SCD) is an inherited disorder secondary to a point mutation at the sixth position of the beta chain of human hemoglobin resulting in the replacement of valine for glutamic acid. This recessive genetic abnormality precipitates the polymerization of the deoxygenated form of hemoglobin S inducing a m...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/ejh.12447
更新日期:2015-05-01 00:00:00
abstract::An unusual case having IgM monoclonal gammopathy with clinical and pathologic features of multiple myeloma (MM) in association with neutrophilia and nephrotic syndrome is reported. The patient showed lytic bone lesions, decreased IgG and IgA levels, Bence-Jones proteinuria, nephrotic proteinuria with edema, and histol...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2007.00869.x
更新日期:2007-07-01 00:00:00
abstract::Several studies have reported data on factors influencing mobilization of peripheral blood stem cells (PBSC) in non-myeloid malignancies. On the contrary, data from patients with acute myeloid leukemia (AML) are very limited, in particular, as the impact of an antecedent diagnosis of refractory anemia with excess blas...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2006.00777.x
更新日期:2007-01-01 00:00:00
abstract::It has been reported that in vitro prednisolone (PDN) resistance provides a prognostic value in childhood acute lymphoblastic leukaemia (ALL). This study aimed at investigating the biological and clinical significance of in vitro PDN resistance in adult ALL. Blast cells from 30 patients were exposed to PDN (0.1 microM...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1996.tb01351.x
更新日期:1996-08-01 00:00:00
abstract:INTRODUCTION/OBJECTIVES:Acute myeloid leukemia (AML) accounts for 90% of all cases of acute leukemia in adults. In Brazil, the mortality from myeloid leukemia is 1.74/100 000 men and 1.37/100 000 women. Our aim was to review and update guidelines of the Brazilian Society of Bone Marrow Transplantation on indications of...
journal_title:European journal of haematology
pub_type: 杂志文章,实务指引
doi:10.1111/ejh.12808
更新日期:2017-02-01 00:00:00
abstract::Relapse represents the most significant cause of failure of allogeneic hematopoietic stem cell transplantation (HSCT) for FLT3-ITD-positive acute myeloid leukemia (AML), and available therapies are largely unsatisfactory. In this study, we retrospectively collected data on the off-label use of the tyrosine kinase inhi...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12647
更新日期:2016-06-01 00:00:00
abstract:PURPOSE:To estimate the clinical significance of low serum concentrations of mannose-binding lectin (MBL) in patients with acute myeloid leukaemia (AML) during initial cancer chemotherapy. PATIENTS AND METHODS:80 consecutive, newly diagnosed, and unselected AML patients (age 18-77 yr) undergoing remission induction ch...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2003.00012.x
更新日期:2003-02-01 00:00:00
abstract:OBJECTIVES:Cord blood (CB) transplantation has advantages in terms of incidence and severity of acute graft-versus-host disease (GVHD), while it has disadvantages in terms of infection. Our aim is to elucidate the molecular mechanism underlying the immune response of CB-derived cells during acute GVHD and infection fol...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1600-0609.2011.01707.x
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVE:The objective of this study was to evaluate the kinetics of molecular response in chronic myeloid leukemia (CML) patients treated with imatinib and to compare between the fluorescent in situ hybridization (FISH), multiplex and real-time quantitative RT-PCR (RQ-PCR) methods with this respect. METHODS:Molecula...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2004.00287.x
更新日期:2004-10-01 00:00:00
abstract:OBJECTIVES:In children with sickle cell disease (SCD), chronic transfusion to maintain haemoglobin S (HbS) below 30% markedly decreases both the risk of a first stroke when transcranial Doppler (TCD) ultrasonography shows abnormal cerebral blood flow velocities and the risk of recurrent stroke. Maintaining HbS below 30...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2009.01379.x
更新日期:2010-03-01 00:00:00
abstract::An automated reticulocyte counter using flowcytometric analysis, the R-3000 (Sysmex Inc. Kobe, Japan), has recently been modified to determine reticulated platelets (RPs) and large platelets (LPs). We measured frequencies of RPs, LPs in total platelet count and serum thrombopoietin concentration comprehensively in non...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1999.tb01131.x
更新日期:1999-11-01 00:00:00
abstract:BACKGROUND:The occurrence of a thrombotic event in congenital bleeding disorders has drawn considerable attention in recent years. Both patients with hemophilia and patients with von Willebrand disease and even those with rare coagulation disorders have been shown to present occasional thrombotic events. Little is know...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12129
更新日期:2013-08-01 00:00:00
abstract:AIMS:Platelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non-valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF o...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12879
更新日期:2017-06-01 00:00:00
abstract::Bcl-2 expression, the number of apoptotic cells and the growth and differentiation of early bone marrow progenitor cells were studied in patients with confirmed diagnosis of acute myeloid leukaemia (AML). Bone marrow cells from normal individuals were used as controls. We observed an increased percentage of bcl-2-mono...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1999.tb01112.x
更新日期:1999-01-01 00:00:00
abstract::Acute tumour lysis syndrome (ATLS) is a well recognised complication of treatment of a variety of malignant disorders. It commonly occurs in patients with non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukaemia (ALL) with the administration of combined cytotoxic chemotherapy. It is rarely reported after single-...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1034/j.1600-0609.2001.066006404.x
更新日期:2001-06-01 00:00:00
abstract:INTRODUCTION:Chimeric antigen receptor (CAR) T cells targeting B cell maturation antigen (BCMA) have shown impressive results in clinical studies for relapsed/refractory multiple myeloma (RRMM). We performed a systematic literature review to summarize the current body of evidence on the role of anti-BCMA CAR T cells fo...
journal_title:European journal of haematology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/ejh.13380
更新日期:2020-04-01 00:00:00
abstract:OBJECTIVES:Hepcidin, a peptide hormone released by hepatocytes into circulation is the main regulator of dietary iron absorption and cellular iron release. Although commercial tests are available, assay harmonization for hepcidin has not been yet reached, making reference intervals and consequent clinical decisions sti...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12081
更新日期:2013-04-01 00:00:00
abstract::Haemophilia remains a complex disorder to diagnose and manage, requiring close cooperation between multidisciplinary healthcare professionals. There are still many unmet challenges in haemophilia care. The first Team Haemophilia Education (THE) meeting, held on 7-8 May 2015 in Amsterdam, The Netherlands, aimed to prom...
journal_title:European journal of haematology
pub_type:
doi:10.1111/ejh.12760
更新日期:2016-07-01 00:00:00
abstract:OBJECTIVES:Secondary antibody deficiency (SAD), associated with severe, recurrent or persistent infections, is common in patients with haematological malignancies (HM), but unifying guidance on immunoglobulin replacement therapy (IgRT) in these patients is lacking. We aimed to develop consensus statements for the use o...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/ejh.13580
更新日期:2021-01-16 00:00:00
abstract::The management of anticoagulant therapy (OAT) in patients with factor VII (FVII) deficiency is a very challenging clinical issue, as warfarin further reduces FVII levels, thus potentially increasing bleeding risk. On the other hand, the International Normalized Ratio test is misleading in such patients, as they do not...
journal_title:European journal of haematology
pub_type: 杂志文章,meta分析
doi:10.1111/ejh.13246
更新日期:2019-07-01 00:00:00
abstract::The use of rituximab is increasing and regular administration over 2 to 3 h requires considerable healthcare resources and is inconvenient for patients. There is interest in reducing rituximab administration times and although infusion of rituximab over 90 min is safe, there is limited data on the safety of 60 min inf...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2009.01215.x
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:Levels of the angiogenic cytokines placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in sickle-cell disease and iron overload, but they have not been evaluated in non-transfusion-dependent thalassemia (NTDT...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.13061
更新日期:2018-06-01 00:00:00
abstract::Monoclonal antibodies 8A and 62B1, recognizing plasma cell-associated antigens, were covalently linked to saporin 6, a ribosome-inactivating protein similar to the A-chain of ricin. Both immunotoxins were tested on target human cell lines U266 and Raji, on non-target K562 cell line and on myeloid CFU-GM progenitors. T...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1989.tb00105.x
更新日期:1989-03-01 00:00:00
abstract::We retrospectively compared the antileukemic effects of chemotherapy alone and chemotherapy followed by modified donor lymphocyte infusion (DLI) in 82 patients with relapsed acute leukemia after haploidentical hematopoietic stem cell transplantation (HSCT) without in vitro T-cell depletion. We also investigated progno...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12168
更新日期:2013-10-01 00:00:00
abstract::The hematopoietic capacity of bone marrow treated with 4-hydroperoxycyclophosphamide (4-HC) was studied using long-term suspension cultures. It was shown that, in the presence of a previously established marrow adherent cell layer (ACL), the 4-HC treated bone marrow, deprived of GM-CFC, generates GM-CFC in long-term s...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1987.tb00740.x
更新日期:1987-08-01 00:00:00
abstract::Physiological mechanisms that regulate formation of neutrophil granulocytes, macrophages and their precursor cells were studied with the diffusion chamber (DC) technique. DC inoculated with mouse bone marrow cells were implanted intraperitoneally into host mice. When these in vivo cultures had been established and the...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1989.tb00245.x
更新日期:1989-01-01 00:00:00
abstract::In 18 beta-thalassaemia families from the Ferrara area the incidence of an inherited low flavin mononucleotide (FMN)-dependent pyridoxine phosphate (PNP) oxidase activity, a sensitive indicator of red-cell FMN deficiency, is higher in related members in these families than in the unrelated spouses and controls subject...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1989.tb01225.x
更新日期:1989-04-01 00:00:00
abstract:OBJECTIVES:To assess the molecular basis of phenotypic heterogeneity in north Indian patients with thalassemia major (TM). METHODS:To determine the clinical severity, 130 patients of TM were studied for the age of first presentation and frequency of blood transfusion. The type of beta mutations, Xmn-1(G)gamma polymorp...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2010.01422.x
更新日期:2010-06-01 00:00:00