Abstract:
:Aberrant expression of aurora kinase A is implicated in the genesis of various neoplasms, including acute myeloid leukemia. Alisertib, an aurora A kinase inhibitor, has demonstrated efficacy as monotherapy in trials of myeloid malignancy, and this efficacy appears enhanced in combination with conventional chemotherapies. In this phase I, dose-escalation study, newly diagnosed patients received conventional induction with cytarabine and idarubicin, after which alisertib was administered for 7 days. Dose escalation occurred via cohorts. Patients could then receive up to four cycles of consolidation, incorporating alisertib, and thereafter alisertib maintenance for up to 12 months. Twenty-two patients were enrolled. One dose limiting toxicity occurred at dose level 2 (prolonged thrombocytopenia), and the recommended phase 2 dose was established at 30mg twice daily. Common therapy-related toxicities included cytopenias and mucositis. Only three (14%) patients had persistent disease at mid-cycle, requiring "5+2" reinduction. The composite remission rate (complete remission and complete remission with incomplete neutrophil recovery) was 86% (nineteen of twenty-two patients; 90% CI 68-96%). Among those over age 65 and those with high-risk disease (secondary acute leukemia or cytogenetically high-risk disease), the composite remission rate was 88% and 100%, respectively. The median follow up was 13.5 months. Of those treated at the recommended phase 2 dose, the 12-month overall survival and progression-free survival were 62% (90% CI 33-81%) and 42% (90% CI 17-65%), respectively. Alisertib is well tolerated when combined with induction chemotherapy in acute myeloid leukemia, with a promising suggestion of efficacy. (clinicaltrials.gov Identifier:01779843).
journal_name
Haematologicajournal_title
Haematologicaauthors
Fathi AT,Wander SA,Blonquist TM,Brunner AM,Amrein PC,Supko J,Hermance NM,Manning AL,Sadrzadeh H,Ballen KK,Attar EC,Graubert TA,Hobbs G,Joseph C,Perry AM,Burke M,Silver R,Foster J,Bergeron M,Ramos AY,Som TT,Fishmdoi
10.3324/haematol.2016.158394subject
Has Abstractpub_date
2017-04-01 00:00:00pages
719-727issue
4eissn
0390-6078issn
1592-8721pii
haematol.2016.158394journal_volume
102pub_type
杂志文章相关文献
HAEMATOLOGICA文献大全abstract:BACKGROUND:The purpose of our cooperative trial was to investigate whether epirubicin (EPI) at 90 mg/m2 in a CHOP-like combination (called CEOP) could increase complete response (CR) and survival rates in non-Hodgkin lymphoma (NHL) patients while maintaining a tolerable degree of toxicity. METHODS:Between September 19...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1995-07-01 00:00:00
abstract::The aim of this study was to identify new pathogenic variations of the UGT1A1 gene in 11 patients diagnosed with neonatal unconjugated hyperbilirubinemia. We describe two cases in which clinically unapparent heterozygotic mutations in the UGT1A1 gene may become evident in combination with certain environmental conditi...
journal_title:Haematologica
pub_type: 信件
doi:10.3324/haematol.10585
更新日期:2007-01-01 00:00:00
abstract::Normal and clonal hematopoietic progenitor cells have been demonstrated to coexist in chronic-phase chronic myelogenous leukemia (CML), but few data are available on the presence of non neoplastic hematopoiesis during the blastic transformation phase. We used reverse transcription-polymerase chain reaction (RT-PCR) to...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Systemic AL amyloidosis, a disease with improving outcomes using novel therapies, is increasingly recognized in the elderly but treatment and outcomes have not been systematically studied in this group of patients in whom comorbidities and frailty may compound morbidity and mortality. We report the outcomes of 295 pat...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:10.3324/haematol.2015.128025
更新日期:2015-11-01 00:00:00
abstract::Hematopoietic differentiation is driven by transcription factors, which orchestrate a finely tuned transcriptional network. At bipotential branching points lineage decisions are made, where key transcription factors initiate cell type-specific gene expression programs. These programs are stabilized by the epigenetic a...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2017.174516
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Imatinib induces complete cytogenetic responses (CCR) in the majority of patients with chronic myeloid leukemia (CML) in chronic phase (CP). However, a subgroup of patients is refractory at the cytogenetic level. Clinically, it would be advantageous to identify such patients a priori, since th...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2005-04-01 00:00:00
abstract::We studied the immune function of 33 long-term survivors of thalassemia after hematopoietic stem cell transplantation. Lymphocyte subsets, lymphoproliferative response and immunoglobulin were normal but the level of natural killer cells was low. Five and seven patients had suboptimal antibody response at 4 week after ...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2003-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:There are no widely accepted criteria for the definition of hematopoietic stem cell transplant -associated microangiopathy (TAM). An International Working Group was formed to develop a consensus formulation of criteria for diagnosing clinically significant TAM. DESIGN AND METHODS:The particip...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10699
更新日期:2007-01-01 00:00:00
abstract::In the European Intergroup EURO-LB02 trial, children and adolescents with lymphoblastic lymphoma underwent the non-Hodgkin lymphoma Berlin-Frankfurt-Münster protocol without prophylactic cranial radiotherapy. The primary aims of this trial were to test whether replacing prednisone with dexamethasone during induction i...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:10.3324/haematol.2015.139162
更新日期:2017-12-01 00:00:00
abstract::A case of thrombotic thrombocytopenic purpura (TTP) in a 40-year-old bisexual man unaware of being HIV positive is reported. The hematologic syndrome represented the first clinical manifestation of this viral infection. The clinical picture, characterized by severe hemolytic microangiopathic anemia, thrombocytopenia, ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative/myelodysplastic disorder associated with mutations in the Ras-Raf-MEK-ERK-signaling pathway. B-Raf plays a central role in this pathway. In 65 screened JMML patients we identified no BRAF mutations and we conclude that this gene is unlikely to play a role...
journal_title:Haematologica
pub_type: 信件
doi:10.3324/haematol.11493
更新日期:2007-11-01 00:00:00
abstract::Hodgkin's lymphoma (HL) simulating acute cholestatic hepatitis is a very unusual clinical picture. Massive liver infiltration with conspicuous acute cholestatic symptoms, in fact, suggests more aggressive systemic diseases such as non Hodgkin's lymphomas or acute leukemias. Nevertheless, we observed two cases of mixed...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Patients with aggressive non-Hodgkin's lymphomas (NHL) who do not obtain a complete response (CR) after induction chemotherapy have a poor prognosis. However, provided they are sensitive to the first regimen of chemotherapy, 25-40% of them with a B-cell phenotype may achieve long-term survival...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:
更新日期:2003-12-01 00:00:00
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::Older chronic lymphocytic leukemia patients have poor outcomes with standard treatments and are underrepresented in clinical trials. We retrospectively reviewed outcomes of refractory chronic lymphocytic leukemia patients in two age categories (≥70 and <70 years) treated with single-agent flavopiridol, a drug active i...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2011.047324
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND:Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. DESIGN AND METHODS:We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2011.044933
更新日期:2011-10-01 00:00:00
abstract::A probabilistic model was used to compare cryoprecipitate to viral inactivated, commercial fibrinogen concentrate to evaluate with regard to the recipient's risk of exposure to an emergent AIDS-like epidemic. In patients who occasionally need a therapeutic dose of fibrinogen, commercial fibrinogen would be marginally ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.11072
更新日期:2007-06-01 00:00:00
abstract::Primary vaginal non-Hodgkin lymphoma is really uncommon and may be misdiagnosed as inflammatory disease or solid cancer, so careful diagnostic procedures are needed, particularly as far as pathological and immunocytochemical evaluation is concerned. Most of these lymphomas present with follicular patterns and limited ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m(2) intravenously on day 1), all-trans retinoic acid (45 mg/m(2) orally on days 4-6 and 15 mg/m(2) orally on days 7-28), high-dose cytarabine (...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.2015.141622
更新日期:2016-07-01 00:00:00
abstract::Genome wide studies have associated TMPRSS6 rs855791 (2321 C>T) with iron status and hepcidin. It is unclear whether this polymorphism affects iron absorption. In nonanemic Taiwanese women (n=79, 44 TT variant, 35 CC variant), we administered standardized rice-based test meals containing 4 mg of labeled 57Fe or 58Fe a...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2020.264556
更新日期:2020-10-05 00:00:00
abstract:BACKGROUND:Granulocyte colony-stimulating factor mobilized peripheral blood stem cells are increasingly used instead of bone marrow as a stem cell source for transplantation. Whereas this change is almost complete for autologous transplantation, there are some concerns when considering allogeneic transplants. DESIGN A...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.2009.006924
更新日期:2009-09-01 00:00:00
abstract::Classical Hodgkin lymphoma is one of the most common lymphomas and shares clinical and genetic features with primary mediastinal B-cell lymphoma. In this retrospective study, we analyzed the recurrent hotspot mutation of the exportin 1 (XPO1, p.E571K) gene, previously identified in primary mediastinal B-cell lymphoma,...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2016.145102
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND:Antithymocyte globulin or human Jurkat T-cell-line-derived antilymphocyte globulin is used in allogeneic stem cell transplantation to induce in vivo T-cell depletion to facilitate engraftment and lower graft-versus-host disease. In vitro studies suggest that antithymocyte globulin, besides causing T-cell dep...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.12665
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Aberrant promoter methylation targets CpG islands causing gene silencing. We explored aberrant promoter methylation of genes potentially involved in B-cell malignancies and encoding proteins implicated in DNA repair (O6-methylguanine-DNA methyltransferase, MGMT), detoxification of environmenta...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2004-02-01 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:alpha thalassemias are very common in all thalassemic areas; however, complete knowledge of the phenotypic, genotypic and epidemiological features of these thalassemias has not yet been achieved for a number of reasons: the frequent absence of a thalassemic hematologic picture, the lack of a specific charact...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::The erythropoietin (Epo)-erythroferrone (ERFE)-hepcidin axis coordinates erythropoiesis and iron homeostasis. While mouse studies have established that Epo-induced ERFE production represses hepcidin synthesis by inhibiting hepatic BMP/SMAD signaling, evidence for the role of ERFE in humans is limited. To investigate t...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2019.233874
更新日期:2021-02-01 00:00:00
abstract::The occurrence of immunoglobulin heavy chain (IgH) and/or T-cell receptor (TcR) gene rearrangements has been reported in some cases of acute non lymphoid leukemia (ANLL), and variously interpreted as reflecting "aberrant gene expression" or "lineage promiscuity" of the leukemic cell. In an attempt to verify the incide...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::Factor V Leiden (FVL) and prothrombin G20210A mutation (PTM) are the two most common genetic polymorphisms known to predispose to a first episode of venous thromboembolism (VTE). However, whether these thrombophilic abnormalities are also risk factors for recurrent VTE is unclear. We conducted a systematic review of p...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:10.3324/haematol.10234
更新日期:2007-08-01 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