Abstract:
:Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key AEs were lower in both arms following the planned reduction of bortezomib dosing frequency in TP2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP1, 56·7%; TP2, 6·0%), diarrhoea (grade 3/4: TP1, 24·1%; TP2, 7·1%), and fatigue (grade 3/4: TP1, 16·3%; TP2, 1·8%) were lower in TP2 compared with TP1. Dose intensity analysis of panobinostat and bortezomib by cycle in the panobinostat arm showed reductions of both agent doses during cycles 1-4 due to dose adjustments for AEs. Exposure-adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
San-Miguel JF,Hungria VTM,Yoon SS,Beksac M,Dimopoulos MA,Elghandour A,Jedrzejczak WW,Guenther A,Na Nakorn T,Siritanaratkul N,Schlossman RL,Hou J,Moreau P,Lonial S,Lee JH,Einsele H,Salwender H,Sopala M,Redhu S,Paul Sdoi
10.1111/bjh.14821subject
Has Abstractpub_date
2017-10-01 00:00:00pages
66-74issue
1eissn
0007-1048issn
1365-2141journal_volume
179pub_type
杂志文章,多中心研究,随机对照试验abstract::Feto-maternal incompatibility for the human platelet antigen HPA-1a is an important cause of severe fetal thrombocytopenia. The incidence is 1 in 1000-2000 pregnancies, which is more common than other conditions for which screening is presently carried out. Antenatal diagnosis and management are now available, but onl...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05152.x
更新日期:1995-06-01 00:00:00
abstract::The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, immunodeficiency and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01694.x
更新日期:1999-11-01 00:00:00
abstract::Thrombopoietin (TPO) is the key growth factor for platelet production and is elevated in states of platelet depletion. As thrombocytopenia is a common finding in malaria, we analysed TPO regulation before, during and after antimalarial treatment. Before treatment, TPO serum levels were significantly higher in patients...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02096.x
更新日期:2000-06-01 00:00:00
abstract::A double-blind, crossover, placebo-controlled study of the effect of vitamin E on platelet functions was performed on nine splenectomized and 16 non-splenectomized beta-thalassaemia/haemoglobin E (beta-thalassaemia/HbE) patients. The patients were supplemented with a daily dose of vitamin E (525 IU) for 3 months. The ...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2141.2003.04691.x
更新日期:2003-11-01 00:00:00
abstract::Myelofibrosis is characterized by splenomegaly and debilitating constitutional symptoms that negatively impact patients' quality of life. ROBUST, a UK, open-label, phase II study, evaluated the safety and efficacy of ruxolitinib in patients with myelofibrosis (N = 48), including intermediate-1 risk patients. The prima...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.13379
更新日期:2015-07-01 00:00:00
abstract::Monoclonal B-cell populations have been detected in the peripheral blood of apparently healthy individuals by flow cytometry. In 2005, the term monoclonal B-cell lymphocytosis (MBL) was proposed to describe these findings. MBL may be immunophenotypically similar to chronic lymphocytic leukaemia (CLL) and, like CLL, th...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06870.x
更新日期:2007-12-01 00:00:00
abstract::We evaluated the level of MCL1 gene expression using quantitative reverse transcription polymerase chain reaction in lymph nodes of patients with non-Hodgkin lymphoma (NHL). MCL1 expression in patients in complete remission (CR) was significantly lower than in patients with progressive disease (PD, P = 0.0043). The di...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03253.x
更新日期:2002-01-01 00:00:00
abstract::High-dose dexamethasone (HD-Dex) has been reported to benefit AL amyloidosis patients with varying response rates. Our preliminary experience with the usual HD-Dex schedule indicated that the induction phase was rather toxic in AL patients. We therefore adopted a milder schedule consisting of dexamethasone 40 mg on d ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02859.x
更新日期:2001-06-01 00:00:00
abstract::FOXP2 mutation causes a severe inherited speech and language defect, while the related transcription factors FOXP1, FOXP3 and FOXP4 are implicated in cancer. FOXP2 mRNA and protein expression were characterised in normal human tissues, haematological cell lines and multiple myeloma (MM) patients' samples. FOXP2 mRNA a...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2009.08070.x
更新日期:2010-04-01 00:00:00
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
doi:10.1046/j.1365-2141.2003.04602.x
更新日期:2003-11-01 00:00:00
abstract::A case of Evans' syndrome with IgM deficiency and lymphopenia was studied before and after splenectomy. The lymphopenia was as a result of profound reduction of CD4 and CD8 cells. Study of cytokine secretion before splenectomy revealed a spontaneous Th1- and Th2-type cytokine production, and complete suppression of tr...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02296.x
更新日期:2000-09-01 00:00:00
abstract::The prognostic relevance of karyotype has been established in adult acute lymphoblastic leukaemia (ALL) patients treated with chemotherapy but not definitively evaluated in an allogeneic bone marrow transplantation (BMT) setting. To determine the factors affecting the outcome of allogeneic BMT for adults with precurso...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03403.x
更新日期:2002-04-01 00:00:00
abstract::Studies of ethnic disparities in malignancies have revealed variation in clinical outcomes. In multiple myeloma (MM), previous literature has focused only on patients of Caucasian and African-American (AA) descent. We present a Surveillance Epidemiology and End Results (SEER)-based outcome analysis of MM patients from...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2012.09124.x
更新日期:2012-07-01 00:00:00
abstract::CD37 is cell surface tetraspanin present on normal and malignant B cells. Otlertuzumab (TRU-016) is a novel humanized anti-CD37 protein therapeutic. Patients with relapsed or refractory follicular non-Hodgkin lymphoma (FL), mantle cell lymphoma (MCL), or Waldenström's macroglobulinaemia (WM) received otlertuzumab at 2...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.13099
更新日期:2015-01-01 00:00:00
abstract::The outcomes of adult patients transplanted for Fanconi anaemia (FA) have not been well described. We retrospectively analysed 199 adult patients with FA transplanted between 1991 and 2014. Patients were a median of 16 years of age when diagnosed with FA, and underwent transplantation at a median age of 23 years. Time...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.15006
更新日期:2018-01-01 00:00:00
abstract::The clonalities in white blood cells (WBC) of blood and nucleated bone marrow cells from patients with refractory anaemia and aplastic anaemia were examined by polymerase chain reaction (PCR) methods using the polymorphic short tandem repeat (STR) on the human androgen-receptor gene (HUMARA). Peripheral blood samples ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb08422.x
更新日期:1995-04-01 00:00:00
abstract::The transformation of lymphocytes in cultures with phytohaemagglutinin (PHA) or with pokeweed mitogen (PWM) was carried out during treatment on 28 patients with paraproteinaemia and on 20 control subjects. 78.5% of the peripheral blood lymphocyte short-term cultures from the treated patients showed a subnormal PHA-ind...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1975.tb01811.x
更新日期:1975-01-01 00:00:00
abstract::Liposome-entrapped desferrioxamine was administered to iron-over-loaded 59Fe lavelled mice. When given orally or intraperitoneally entrapment did not enhance the effect of the chelator, but given intravenously liposomal desferrioxamine doubled the 59Fe excretion for a given dose of the drug, and excretion after a sing...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb05868.x
更新日期:1979-03-01 00:00:00
abstract::Thrombocytopenia and neutropenia are common among neonates in intensive care units. Bone marrow aspirations are sometimes performed as part of their evaluation. However, marrow biopsies have not been reported from living neonates. Since architecture and cellularity cannot generally be accurately assessed from marrow a...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01712.x
更新日期:1999-11-01 00:00:00
abstract::Myelodysplastic syndrome (MDS) is a common neoplasm of haematopoietic pluripotent stem cells. Although one third of MDS patients evolve to acute myeloid leukaemia (AML), little is understood about the mechanisms responsible for this progression. We have previously detected the frequent loss of heterozygosity (LOH) on ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04434.x
更新日期:2003-07-01 00:00:00
abstract::Chimaerism was studied early (2 weeks to 3 months) during haematopoietic reconstitution after bone marrow transplantation in 18 severe aplastic anaemia patients (acquired SAA: 14 patients; Fanconi anaemia: four patients). Fourteen patients received marrow from an identical sibling donor, one from the phenoidentical fa...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb08150.x
更新日期:1992-03-01 00:00:00
abstract::Pulmonary hypertension (PH) can complicate myelofibrosis with myeloid metaplasia (MMM), may arise in the absence of evidence for thromboembolic disease and carries a grim prognosis. Four patients with MMM and severe symptomatic PH were treated with whole-lung external beam radiotherapy in a single fraction of 100 cGy....
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03695.x
更新日期:2002-09-01 00:00:00
abstract::Parental longevity is associated with an increased life expectancy; results with regard to specific diseases are conflicting. There are limited data focusing on host characteristics and their effect on survival among multiple myeloma (MM) patients and individuals with monoclonal gammopathy of undetermined significance...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.15883
更新日期:2019-07-01 00:00:00
abstract::There is evidence for increased factor VII turnover and the associated increased thrombin generation and fibrinolytic activities in sickle cell disease (SCD) that may affect in vivo platelet and endothelial cell reactivity. We studied the release of specific eicosanoids that are indicative of in vivo platelet activati...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb08316.x
更新日期:1994-07-01 00:00:00
abstract::The combined incidence of classical Philadelphia-negative myeloproliferative neoplasm (MPN) is 6-9/100 000 with a peak frequency between 50 and 70 years. MPN is less frequent in women of reproductive age. However, for essential thrombocythaemia (ET) in particular there is a second peak in women of reproductive age and...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.16453
更新日期:2020-05-01 00:00:00
abstract::Aplastic anaemia (AA) is considered as an immune-mediated bone marrow failure syndrome. The mechanism is involved with a variety of immune molecules including interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and interleukins (ILs). IL-27 is a novel member of the IL-12 family, which mediates T cell response and e...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2010.08431.x
更新日期:2011-06-01 00:00:00
abstract::We have tested the different mononuclear blood cell populations of seven patients with severe haemophilia and one patient with F VII deficiency for the presence of HBV DNA. These subjects were all polytransfused with non-heated coagulation factors; three were HBsAg positive, five HBsAg negative but anti-HBc and anti-H...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb02262.x
更新日期:1987-02-01 00:00:00
abstract::Glucocorticoid (GC) effects are mediated by the glucocorticoid receptor (GR). Several studies have demonstrated that a lower number of receptors per cell were associated with poor GC response. The regulation of GR expression is complex; the levels of GR can be autologously regulated by its ligand and also by transcrip...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2008.07549.x
更新日期:2009-03-01 00:00:00
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 ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.16088
更新日期:2019-11-01 00:00:00
abstract::Cardiopulmonary bypass (CPB) induces a bleeding defect which leads to enhanced blood loss. A double-blind study was carried out comparing aprotinin with placebo in patients undergoing re-operation for heart valve replacement. The results confirm that aprotinin is effective at reducing such loss. In the placebo treated...
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.1365-2141.1993.tb03344.x
更新日期:1993-11-01 00:00:00