Abstract:
:Hematologic responses to hypomethylating agents are often delayed in patients with myelodysplastic syndrome or acute myeloid leukemia. Fetal hemoglobin is a potential novel bio-marker of response: recently, we demonstrated that a high fetal hemoglobin level prior to decitabine treatment was associated with superior outcome. Here we investigated whether early fetal hemoglobin induction during decitabine treatment also had prognostic value, and studied the potential of decitabine to induce erythroid differentiation and fetal hemoglobin expression in vitro Fetal hemoglobin levels were measured by high-performance liquid chromatography in patients with higher-risk myelodysplastic syndrome (n=16) and acute myeloid leukemia (n=37) before treatment and after each course of decitabine. Levels above 1.0% were considered induced. Patients achieving complete or partial remission as best response had attained a median fetal hemoglobin of 1.9% after two courses of treatment, whereas the median value in patients who did not reach complete or partial remission was 0.8% (P=0.015). Fetal hemoglobin induction after two courses of decitabine treatment was associated with early platelet doubling (P=0.006), and its subsequent decrease with hematologic relapse. In patients with myelodysplastic syndrome, induction of fetal hemoglobin after course 2 of treatment was associated with longer overall survival: median of 22.9 versus 7.3 months in patients with or without induction of fetal hemoglobin, respectively [hazard ratio=0.2 (95% confidence interval: 0.1-0.9); P=0.03]. In vitro decitabine treatment of two bi-potential myeloid leukemia cell lines (K562 and HEL) resulted in induction of an erythroid (not megakaryocytic) differentiation program, and of fetal hemoglobin mRNA and protein, associated with GATA1 gene demethylation and upregulation. In conclusion, fetal hemoglobin may provide a useful dynamic biomarker during hypomethylating agent therapy in patients with myelodysplastic syndrome or acute myeloid leukemia.
journal_name
Haematologicajournal_title
Haematologicaauthors
Stomper J,Ihorst G,Suciu S,Sander PN,Becker H,Wijermans PW,Plass C,Weichenhan D,Bissé E,Claus R,Lübbert Mdoi
10.3324/haematol.2017.187278subject
Has Abstractpub_date
2019-01-01 00:00:00pages
59-69issue
1eissn
0390-6078issn
1592-8721pii
haematol.2017.187278journal_volume
104pub_type
临床试验,杂志文章相关文献
HAEMATOLOGICA文献大全abstract::The last decade has witnessed great advances in our understanding of the genetic and biological basis of childhood acute lymphoblastic leukemia (ALL), the development of experimental models to probe mechanisms and evaluate new therapies, and the development of more efficacious treatment stratification. Genomic analyse...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2020.247031
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Recently, a chimeric monoclonal antibody (MoAb) directed against the CD20 antigen (rituximab) has been successfully introduced in the treatment of several CD20-positive B-cell neoplasias and particularly of follicular lymphomas. Based on these premises we evaluated the efficacy and the toxicit...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::Chronic lymphocytic leukemia is frequently associated with immune disturbances. The relationship between chronic lymphocytic leukemia and autoimmune cytopenias, particularly autoimmune hemolytic anemia and immune thrombocytopenia, is well established. The responsible mechanisms, particularly the role of leukemic cells...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:10.3324/haematol.2010.036152
更新日期:2011-05-01 00:00:00
abstract::Home care (HC) has an increasingly expanding role in the global management of patients affected by hematologic malignancies. Integrated strategies, including causal-targeted and supportive treatments according to hematologic expertise and a holistic approach inspired by the philosophy and practice of palliative medici...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:von Willebrand's disease (vWD) is a bleeding disorder with variable clinical expression. Our aim was to classify patients with vWD and to determine the phenotype in their relatives. DESIGN AND METHODS:The types and subtypes, blood group frequency and its relevance, bleeding sites, response to...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::Rituximab has improved response rates and overall survival in B-cell lymphoma (DLBCL). Radiotherapy is an effective treatment modality for lymphomas, but there is uncertainty on its use as consolidation after chemo-immunotherapy mainly in advanced stages. We evaluated its efficacy with a comprehensive meta-analysis an...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2020.249680
更新日期:2020-06-18 00:00:00
abstract::Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. The clinical spectrum of the thalassemia syndrome ranges from the severe, transfusion--dependent thalassemia major and the asymptomatic carrier state. Thalassemia intermedia represents a milder form and is usua...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:10.3324/haematol.10915
更新日期:2007-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Oxidant damage is an important contributor to the premature destruction of erythrocytes and anemia in thalassemias. To assess the extent of oxidant damage of circulating erythrocytes and the effects of antioxidant therapy on erythrocyte characteristics and anemia, we used a mouse model of huma...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2004-11-01 00:00:00
abstract::The discovery that the Ten-Eleven Translocation (TET) hydroxylases cause DNA demethylation has fundamentally changed the notion of how DNA methylation is regulated. Clonal analysis of the hematopoetic stem cell compartment suggests that TET2 mutations can be early events in hematologic cancers and recent investigation...
journal_title:Haematologica
pub_type: 杂志文章,随机对照试验
doi:10.3324/haematol.2013.088740
更新日期:2013-12-01 00:00:00
abstract::Iron overload and hepatitis virus C infection cause liver fibrosis in thalassemics. In a monocentric retrospective analysis of liver disease in a cohort of 191 transfusion-dependent thalassemics, in 126 patients who had undergone liver biopsy (mean age 17.2 years; 58 hepatitis virus C-RNA positive and 68 hepatitis vir...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.12554
更新日期:2008-08-01 00:00:00
abstract::Phase I/II studies of gemtuzumab ozogamicin (GO) in pediatric refractory/relapsed acute myeloid leukemia (AML) have been reported. We present the cases of two children with relapsed AML who were treated with GO plus cytarabine, leading to a decrease of minimal residual disease down to levels not previously obtained. T...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2006-03-01 00:00:00
abstract::It is currently unknown whether immunosuppressive therapy or hematopoietic stem cell transplantation is the most appropriate treatment strategy for children with refractory cytopenia and normal karyotype or trisomy 8. We report on 31 children with hypoplastic refractory cytopenia treated with immunosuppressive therapy...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10683
更新日期:2007-03-01 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::Second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease remains ill-defined, due to limited efficacy of drugs and evolving clinical trial endpoints. Six-month freedom from treatment failure has been proposed as a novel clinical trial endpoint and is defined by the absence of dea...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2014.108217
更新日期:2014-11-01 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:BACKGROUND:Usefulness of iron chelation therapy in myelodysplastic patients is still under debate but many authors suggest its possible role in improving survival of low-risk myelodysplastic patients. Several reports have described an unexpected effect of iron chelators, such as an improvement in hemoglobin levels, in ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2009.016824
更新日期:2010-08-01 00:00:00
abstract::Chronic graft-versus-host disease is a serious complication in long-term survivors of allogeneic hematopoietic stem cell transplantation, with several organ systems affected. Chronic graft-versus-host disease is an important cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation. This a...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.13311
更新日期:2008-11-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The mechanisms accounting for the increased risk of thrombosis in patients with essential thrombocythemia (ET) are not well known. The aim of the present study was to ascertain the role of platelet and leukocyte activation in the thrombosis of ET. DESIGN AND METHODS:The activation status of p...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2006-02-01 00:00:00
abstract::Mastocytosis is a rare and chronic disease with phenotypes ranging from indolent to severe. Prognosis for this disease is variable and very few biomarkers to predict disease evolution or outcome are currently known. We have performed comprehensive screening in our large cohort of mastocytosis patients for mutations pr...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.2013.095133
更新日期:2014-05-01 00:00:00
abstract::The long-term repopulating capacity of mobilized peripheral blood (MPB) CD34+ cells can be abrogated during ex vivo expansion due to cell-cycle related changes. In this study, we traced cell cycle kinetic and quiescent status of CD34+ cells during ex vivo expansion with exogenous cytokines. The addition of interleukin...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2006-01-01 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:BACKGROUND:In normal platelets, insulin inhibits agonist-induced Ca(2+) mobilization by raising cyclic AMP. Platelet from patients with type 2 diabetes are resistant to insulin and show increased Ca(2+) mobilization, aggregation and procoagulant activity. We searched for the cause of this insulin resistance. DESIGN AN...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2011.054916
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:The risk for donors of allogeneic hematopoietic stem cells transplants is generally considered negligible. Scattered reports of severe complications and a recent controversy on hematopoietic malignancies after granulocyte colony-stimulating factor administration have challenged this opinion. DESIGN AND METH...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.13668
更新日期:2009-01-01 00:00:00
abstract::BACKGROUND. Hypofibrinogenemia and increased fibrin(ogen) degradation products in acute leukemia have been attributed to intravascular thrombin generation triggered by leukemic cells. However, the strict relationship between fibrinogen catabolism and turnover of fibrinopeptide A (FPA), which is a sensitive and specifi...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:The expression of CD36 antigen has not been conclusively associated with human B-lymphocytes although CD36 was recently detected in a human B-cell angiotropic lymphoma where it might be involved in lymphoblast-endothelial cell adhesion. We investigated the expression of CD36 in B-cell chronic l...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial acti...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2015.136630
更新日期:2016-05-01 00:00:00
abstract::We describe the case of a 12-year old boy with Hoyeraal-Hreidarsson Syndrome (HHS). This syndrome includes intrauterine growth retardation, microcephaly, mental retardation, cerebellar malformation, and pancytopenia. HHS is a severe multisystem disorder associated with premature mortality, due to bone marrow failure. ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
abstract::Epidemiological evidence suggests that infection is involved in the etiology of common acute lymphoblastic leukemia, either by stimulating an inappropriate immune response or in the form of a classical transforming agent. In an attempt to elucidate the role that infection is playing in this disease, we used representa...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2006-02-01 00:00:00
abstract::One hundred thirty-three febrile episodes in 115 neutropenic patients with hematologic malignancies were empirically treated with ceftriaxone and amikacin in a single daily dose. An indwelling central venous catheter (CVC) was present in 44 cases. Septicemia was documented in 18 (41%) patients with CVC (13 gram-positi...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall su...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.3324/haematol.2014.117077
更新日期:2015-10-01 00:00:00