Abstract:
PURPOSE:To determine the safety, dose-limiting toxicity and maximum tolerated dose (MTD) of the novel hydroxamate histone deacetylase inhibitor belinostat (PXD101) in patients with advanced hematological neoplasms. PATIENTS AND METHODS:Sequential dose-escalating cohorts of three to six patients with hematological malignancies received belinostat administered as a 30-min i.v. infusion on days 1-5 of a 21-d cycle. Experience from a parallel dose-finding study in patients with solid tumors influenced the selection of the final dose. RESULTS:Sixteen patients received belinostat at one of three dose levels: 600 mg/m(2)/d (three patients), 900 mg/m(2)/d (three patients) and 1000 mg/m(2)/d (10 patients), the dose determined to be the MTD in a phase I solid tumor study [Steele et al. (2008) Clin Cancer Res, 14, 804-10]. The most common treatment-related adverse events (all grades) were nausea (50%), vomiting (31%), fatigue (31%) and flushing (31%). No grade 3 or 4 hematological toxicity compared with baseline occurred except one case of grade 3 lymphopenia. There were two related grade 4 adverse events of renal failure observed. Both events occurred in patients with multiple myeloma and had similar characteristics, i.e. an acute episode of decrease in renal function (pre-existing nephropathy in one patient), with a metabolic profile and decrease in tumor burden consistent with tumor lysis syndrome. No other related grade 4 events were noted. The only related grade 3 events noticed in more than one patient were fatigue and neurological symptoms (one patient had status epilepticus in association with uremia and one patient had paresthesia), all other related grade 3 events occurred in single patients. No cardiac events were noted. No complete or partial remissions were noted in these heavily pre-treated (median of four prior regimens) patients. However, five patients, including two patients with diffuse large-cell lymphoma [including one patient with transformed chronic myelocytic leukaemia (CLL)], two patients with CLL and one patient with multiple myeloma, achieved disease stabilization in of two to nine treatment cycles. CONCLUSIONS:Intravenous belinostat at 600, 900 and 1000 mg/m(2)/d is well tolerated by patients with hematological malignancies. The study was carried out in parallel to a similar dose-finding study in patients with solid tumors, in which the MTD was determined to be 1000 mg/m(2)/d days 1-5 in a 21-d cycle. This dose can also be recommended for phase II studies in patients with hematological neoplasms.
journal_name
Eur J Haematoljournal_title
European journal of haematologyauthors
Gimsing P,Hansen M,Knudsen LM,Knoblauch P,Christensen IJ,Ooi CE,Buhl-Jensen Pdoi
10.1111/j.1600-0609.2008.01102.xsubject
Has Abstractpub_date
2008-09-01 00:00:00pages
170-6issue
3eissn
0902-4441issn
1600-0609pii
EJH1102journal_volume
81pub_type
杂志文章,多中心研究abstract::Angiogenesis is critical for the clinical progression of haematopoietic malignancies and depends on angiogenic factors. Angiogenin is a powerful factor produced by neoplastic cells and host microenvironment. High levels of soluble angiogenin (sAng) correlate with a poor prognosis in patients affected by acute myeloid ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2004.00253.x
更新日期:2004-06-01 00:00:00
abstract::Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1600-0609.1992.tb00030.x
更新日期:1992-08-01 00:00:00
abstract::Most cytostatic drugs exert their effect on cells in active cell cycle. To improve the effect of cytostatic drugs we have tried, prior to treatment in vitro, to recruit tumor cells from G0 with growth factors. Leukemic cells from the bone marrows of 26 patients with AML and CML in blast crisis were incubated with G-CS...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1996.tb00285.x
更新日期:1996-01-01 00:00:00
abstract::Karyotype analysis of bone marrow samples was performed in 20 cases of essential thrombocythemia (ET) at the time of diagnosis. Three patients had karyotype abnormalities at the time of diagnosis; trisomy 8, deletion of Y, and del(9)(q?) in each. The patient who had trisomy 8 at the time of diagnosis underwent myeloid...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2002.01601.x
更新日期:2002-02-01 00:00:00
abstract::The clinicopathological features of human immunodeficiency virus (HIV)-associated lymphoma were investigated in a retrospective study of 85 adult patients in eastern Denmark diagnosed during the period 1990-1996. The possible pathogenetic role of Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) in these tumour...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2000.90126.x
更新日期:2000-06-01 00:00:00
abstract::Heparin binds to platelets and can cause platelet proaggregating and potentiating effects, possibly causing thrombocytopenia, particularly in patients in intensive care with hyperaggregable platelets. In this study we compared the platelet proaggregating and potentiating effects of unfractionated heparin (UH), 2 low m...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1997.tb01667.x
更新日期:1997-04-01 00:00:00
abstract::The molecular defects of the factor XIII A subunit gene were studied in a patient with factor XIII deficiency. Mutation analysis was performed on amplified DNA from each exon of this gene by single-strand conformation polymorphism (SSCP) and DNA sequencing techniques. A substitution of guanine by adenine at nucleotide...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2000.065004279.x
更新日期:2000-10-01 00:00:00
abstract::We evaluated the serum/plasma levels of cytokines [interleukin (IL)-6, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta2] and markers of coagulation, fibrinolysis, endothelial and platelet activation during the first 4 wk of treatment with the thalidomide analogue Actimid (CC-4047) in 1...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2004.00393.x
更新日期:2005-04-01 00:00:00
abstract::The thalassemia syndromes (α- and β-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or β-globin chain production results in impaired red blood cell synthesis, anemia, and more erythroid progenitors in the blood stream. While patients affected by these...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12464
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVES:This study aims to characterize the epidemiology of immunocompetent Primary central nervous system lymphoma (PCNSL) diagnosed 2000-2013 in Sweden. METHODS:Cases were identified in the population-based Swedish Lymphoma Register. Incidence per 100 000 person-years and 95% confidence intervals (CI) were calcul...
journal_title:European journal of haematology
pub_type: 历史文章,杂志文章
doi:10.1111/ejh.12980
更新日期:2018-01-01 00:00:00
abstract::This study was conducted in order to assess myocardial and liver iron concentrations (LICs) using serial magnetic resonance imaging (MRI) scans in patients with beta-thalassaemia major, over a 4-yr period, and consequently to compare the effectiveness of different chelation regimens. Fifty children and young adults wi...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.0902-4441.2006.t01-1-EJH3013.x
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVES:Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 ( FLT3) gene occur in 13-35% of patients with acute myeloid leukemia (AML). FLT3-ITD is associated with poor clinical outcome and is an indication for allogeneic stem cell transplantation (allo-SCT). METHODS:To investigate FLT3-ITD length...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2012.01785.x
更新日期:2012-07-01 00:00:00
abstract::This report describes a family with TUBB1-associated macrothrombocytopenia diagnosed based on abnormal platelet β1-tubulin distribution. A circumferential marginal microtubule band was undetectable, whereas microtubules were frayed and disorganized in every platelet from the affected individuals. Patients were heteroz...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12252
更新日期:2014-04-01 00:00:00
abstract:OBJECTIVE:Interferon-alpha (IFNalpha) was the first effective pharmacologic treatment of hairy cell leukemia (HCL). Since 1990 purine analogs replaced IFNalpha because of higher rates of complete remission and an invariable disease recurrence after cessation of IFNalpha. However, there are only limited data about long-...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2008.01190.x
更新日期:2009-03-01 00:00:00
abstract::In acute myeloid leukemia (AML) mouse models, the RUNX1-RUNX1T1 fusion protein has failed to produce leukemia by itself, but alternative splicing of exon 9a of the RUNX1-RUNX1T1 fusion transcript (FT) has recently been shown to enhance the leukemogenic potential. We have analyzed 138 diagnosis and follow-up samples fr...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2009.01371.x
更新日期:2010-02-01 00:00:00
abstract::Propagation of the vaso-occlusive process in sickle cell anaemia (SCA) is a complex process involving the adhesion of steady-state SCA patients red cells and reticulocytes to the vascular endothelium. The effect of hydroxyurea therapy (HUT) on the adhesive properties of sickle cells and the expression of adhesion mole...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2006.00788.x
更新日期:2007-02-01 00:00:00
abstract::Haemoglobin (Hb) Hope [beta136(H14)Gly-->Asp(GGT-->GAT)] is one of the unstable haemoglobin variants of the beta-globin chain, which is demonstrated in people of various ethnic backgrounds. Here we report a Thai female patient with clinical thalassaemia intermedia since childhood. This patient had experienced neither ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2007.00907.x
更新日期:2007-09-01 00:00:00
abstract::Mononuclear phagocytes play an important role in the regulation of hematopoiesis, not only by producing regulatory monokines such as prostaglandins, tumor necrosis factor and interleukin-1 (IL-1), but also by the production of colony-stimulating activity (CSA). Previously, we have demonstrated that granulocyte-macroph...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1988.tb00209.x
更新日期:1988-10-01 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::Recombinant human erythropoietin (rhEpo) is a mainstay in the treatment of anaemia, primarily in renal failure. Because the half-life of circulating rhEpo is relatively short (4-8 h), the drug is usually administered 2-3 times weekly. Recently, a novel erythropoiesis-stimulating protein (NESP) with a longer half-life ...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1034/j.1600-0609.2002.02813.x
更新日期:2002-11-01 00:00:00
abstract::Antigenic concentration of total kininogen, kinin liberated in vitro, and the antigenic concentration of high molecular weight (HMW) kininogen was measured in 58 different samples of cord blood plasma and in plasma samples from 67 healthy blood donors. Total kininogen and kinin concentration in cord blood plasma was m...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1991.tb01536.x
更新日期:1991-05-01 00:00:00
abstract:OBJECTIVE:Warfarin represents the most commonly prescribed oral anticoagulants, which functions as an antagonist of vitamin K, an essential factor of blood coagulation cascade. Warfarin has a narrow therapeutic index. An insufficient dose can cause failure of antithrombotic effect, and an overdose increases a risk of b...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12348
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:Although allogeneic hematopoietic cell transplantation (HCT) has a potential to cure patients with paroxysmal nocturnal hemoglobinuria (PNH), appropriate indication and conditioning regimen for HCT have not been established. PATIENTS AND METHODS:Between July 1999 and December 2001, five patients with PNH un...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1034/j.1600-0609.2003.00097.x
更新日期:2003-08-01 00:00:00
abstract:OBJECTIVE:For transplantation of cord blood (CB) cells, it is important to select a CB sample that can reconstitute not only myelo-erythropoiesis but also lymphopoiesis in recipients. However, until now the reconstitution ability of CB samples has been assessed by colony forming unit-culture (CFU-C) assay or by simply ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2007.00991.x
更新日期:2008-02-01 00:00:00
abstract::Plasma and cellular pharmacokinetics of m-AMSA were investigated in 5 patients with acute leukemia, using HPLC. The pharmacokinetic data served as a guideline for in vitro toxicity tests on clonogenic bone marrow cells. m-AMSA was administered as a 3-hour intravenous infusion of 100 mg/m2. Median plasma and nucleated ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1993.tb00083.x
更新日期:1993-03-01 00:00:00
abstract:OBJECTIVE:To correlate different polymorphisms of the beta-globin cluster with fetal hemoglobin (HbF) level in beta-thalassemia and E-beta thalassemia patients. METHODS:Fifteen thalassemia patients, seven with high HbF and not requiring transfusion, eight with lower HbF and requiring transfusion were studied for beta-...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2005.00416.x
更新日期:2005-07-01 00:00:00
abstract::Administration of both glycosylated and non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) induces an immediate transient granulocytopenia of 1-3 hours' duration. In order to explore this phenomenon, granulocytes were labelled with 111Indium and the effect on the kinetics of...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1600-0609.1992.tb01586.x
更新日期:1992-04-01 00:00:00
abstract::Between December, 1984, and May, 1986, 98 CSF samples were sent to a central laboratory by postal express. The samples could be kept in a medium for up to 24 hours after the lumbar puncture. The quality of the cells proved to be good. Excluded were 5 samples delayed in delivery and 13 samples contaminated with blood, ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1988.tb00832.x
更新日期:1988-03-01 00:00:00
abstract::Isolated myeloid sarcoma is a rare presentation of acute myeloid leukemia. There are limited data available concerning the prognostic relevance and the right treatment strategy for this clinical scenario. Here, we report a case of acute myeloid leukemia with extensive lesions and fractures in multiple bones in a 64-yr...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12254
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:To evaluate the activation of clotting systems in patients with sickle cell disease (SCD) by measuring the plasma D-dimer level and to determine the effect of low-dose warfarin on D-dimer level during vaso-occlusive crisis. METHODS:Plasma D-dimer level was measured in 65 blood samples of 37 adult patients wi...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.0902-4441.2003.00209.x
更新日期:2004-03-01 00:00:00