Abstract:
:Imatinib (Gleevec) (formerly STI571) is an orally bioavailable rationally developed inhibitor of the tyrosine kinases Bcr-Abl, Kit, and platelet-derived growth factor receptor (PDGFR). In 4 years of clinical development, more than 12,000 patients have been treated in the clinical development program. Imatinib was first shown to be highly effective in the treatment of all stages of chronic myelogenous leukemia (CML). Moreover, preliminary results of a randomized study have demonstrated superior efficacy and safety of first-line imatinib therapy compared with a combination of interferon and cytarabine. Imatinib has also been shown to be the only effective drug therapy in the treatment of patients with metastatic gastrointestinal stromal tumors expressing the stem cell factor (SCF) receptor Kit. This review outlines the successive steps in the clinical development of this new, targeted anticancer agent.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
Capdeville R,Silberman Sdoi
10.1053/shem.2003.50037subject
Has Abstractpub_date
2003-04-01 00:00:00pages
15-20issue
2 Suppl 2eissn
0037-1963issn
1532-8686pii
S0037196303000702journal_volume
40pub_type
杂志文章,评审abstract::Peripheral suppression of autoreactive T cells by specialized T-cell populations is one of several mechanisms ensuring self-tolerance within the adaptive immune system. Thymus-derived CD4+CD25+ T cells expressing the transcriptional repressor FOXP3 mediate such immunoregulatory functions and are pivotal for the preven...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2005.09.006
更新日期:2006-01-01 00:00:00
abstract::The central hypothesis of our laboratory research program in large granular lymphocyte (LGL) leukemia is that leukemic LGL represent antigen-driven cytotoxic T lymphocytes (CTL) with characteristics of dysregulated apoptosis. The clinical features of LGL leukemia highlight the association of autoimmune diseases such a...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(03)00135-5
更新日期:2003-07-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) comprises a substantial proportion of leukemias in adults in the western hemisphere. Male gender, increasing age, ethnicity (high in Caucasians, lowest in Asians), and family history are risk factors. Although no specific extrinsic etiologic factors have been established, farming and...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2004.05.002
更新日期:2004-07-01 00:00:00
abstract::A retrospective study was conducted to determine treatment patterns for idiopathic thrombocytopenia purpura (ITP) across the US and to determine the cost of its treatment with high-dose intravenous immunoglobulin (IVIg) and anti-D therapy. Information on the incidence, treatment patterns, hospital care, and costs for ...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Myelofibrosis with myeloid metaplasia, also known as idiopathic myelofibrosis (IF) or agnogenic myeloid metaplasia, is one of the characteristic manifestations of polycythemia vera (PV) in the spent phase, and has a particularly adverse prognosis. IF may also present de novo. To date, treatment strategies for both spe...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2003.50032
更新日期:2003-01-01 00:00:00
abstract::From a computational perspective, Bayesian methods can be viewed as a natural extension of familiar confidence intervals and significance tests, which sheds light on their meaning. This viewpoint shows that no special software is required to compute Bayesian results, leaving the distinctions between conventional and B...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:10.1053/j.seminhematol.2008.04.004
更新日期:2008-07-01 00:00:00
abstract::Thrombus forms on catheters and other indwelling synthetic materials. Systemic heparin infusion decreases, but does not eliminate thrombus formation. The day is approaching when systemic heparinization may no longer be indicated to suppress catheter thrombogenesis. Passivation of catheters by heparin immobilization is...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1991-10-01 00:00:00
abstract::Large scale sequencing projects over the past 2 decades have led to the identification of many common genomic alterations in hematolymphoid neoplasms, some of which with diagnostic, therapeutic, and prognostic implications [1-3]. Although these alterations can be tested individually with high sensitivity and specifici...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2018.05.006
更新日期:2019-01-01 00:00:00
abstract::The standard treatment of multiple myeloma is systemic chemotherapy. Despite 30 years of drug development in myeloma, there are no new drug regimens significantly superior to melphalan and prednisone. In addition, phase II studies of new drugs in myeloma have been disappointing, with low response rates and no prolonga...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1998-07-01 00:00:00
abstract::This phase I trial of idarubicin (IDA) was conducted in 32 patients with acute leukemia and chronic myelogenous leukemia (CML) in blastic crisis (CML/BC) who either had failed to achieve a complete remission (CR) after initial induction therapy or had relapsed after CR. IDA was administered at dosages ranging from an ...
journal_title:Seminars in hematology
pub_type: 临床试验,杂志文章,评审
doi:
更新日期:1996-10-01 00:00:00
abstract::Copper is an essential trace element that is required for a number of enzymes which are necessary for normal metabolic function. Metabolic balance studies have demonstrated that daily copper losses are approximately 1.3 mg/day. In order to remain in copper balance, the average adult male must consume a diet which cont...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1983-04-01 00:00:00
abstract::Continuous daily treatment with all-trans-retinoic acid (ATRA) in patients with acute promyelocytic leukemia has been associated with a marked decline in the plasma drug concentration at the time of relapse. Recent pharmacologic studies have attempted to determine the reasons for the progressive reduction of plasma co...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1994-10-01 00:00:00
abstract::In previous studies, treatment with epoetin alfa facilitated preoperative donation of autologous blood (AB). However, some patients may not be able to donate sufficient AB to meet their surgical blood requirements when the time to surgery is short. In this multicenter, double-blind, placebo-controlled study, the abili...
journal_title:Seminars in hematology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1996-04-01 00:00:00
abstract::The availability of antibodies reactive with antigens expressed only by hematopoietic cells has provided clinical investigators with new tools for use in developing therapies for acute myeloid leukemia (AML). Studies performed to date have investigated the use of such antibodies in an unmodified state, combined with p...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::Thrombocytopenia is common among sick neonates, affecting 20% to 35% of all patients admitted to the neonatal intensive care unit (NICU). While most cases of neonatal thrombocytopenia are mild or moderate and resolve within 7 to 14 days with appropriate therapy, 2.5% to 5% of NICU patients develop severe thrombocytope...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2010.04.002
更新日期:2010-07-01 00:00:00
abstract::Thrombocytopenia is one of the most common reasons for inpatient hematology consultations. The main challenges in the management of hospitalized patients with thrombocytopenia are to identify the underlying cause and to recognize when urgent interventions are required. Examination of the blood film is essential in the...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2011.08.002
更新日期:2011-10-01 00:00:00
abstract::A new high-purity recombinant factor VIII preparation has been developed for the treatment of hemophilia A. Structurally, this factor VIII preparation, B-domain deleted recombinant factor VIII (BDDrFVIII), differs from other recombinant and plasma-derived factor VIII preparations in that most of the B-domain has been ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(01)90103-9
更新日期:2001-04-01 00:00:00
abstract::Inhibition of antibody-coated platelet destruction in patients with immune thrombocytopenic purpura (ITP) is a well-known mechanism of treatment effect. A number of interventions that would ameliorate the thrombocytopenic effect of ITP patient plasma when infused into normal recipients were demonstrated in 1965. Subse...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(00)90104-5
更新日期:2000-07-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is a clonal proliferation of mature-appearing, but maturationally immature B cells; T cells are rarely involved. Most data suggest that CLL cells are frozen at an early step in maturation; this can be overcome by several techniques such as in vitro incubation with tumor promotors. Al...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1987-10-01 00:00:00
abstract::From work particularly In the last two decades of the century, the cell populations forming blood cells can now be purified and cultured clonally so that blood cell formation can be analyzed in vitro. A large number of specific regulators of this process have been identified and mass-produced in recombinant form. Thre...
journal_title:Seminars in hematology
pub_type: 历史文章,杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::In the era of modern communication, the physician and patient relationship has evolved to include an entirely new dimension-social media. This new dimension offers several opportunities for patient education, research and its dissemination, and professional development for health care providers; it can also serve as a...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2017.07.003
更新日期:2017-10-01 00:00:00
abstract::Despite the development of more effective therapies for multiple myeloma (MM) over the past decade, nearly all patients will eventually experience disease relapse and require further therapy. Designing the next generation of therapies for relapsed and refractory disease will depend on understanding the complex molecul...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:10.1053/j.seminhematol.2012.05.005
更新日期:2012-07-01 00:00:00
abstract::Since warfarin remains the predominate drug administered for long-term anticoagulation, optimizing therapy for maximum antithrombotic effect with minimal bleeding risk continues to challenge clinicians. Genetic differences exist that affect an individual's response to warfarin. The clinician can use genetic informatio...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2002.34089
更新日期:2002-07-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by ineffective hematopoiesis resulting in peripheral cytopenia and by increased progression to acute myelocytic leukemia (AML). With the exception of allogeneic stem cell transplantation, there is generally no curative treatment for these d...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2004.02.002
更新日期:2004-04-01 00:00:00
abstract::This article summarizes clinical results of the Intergroupe Francophone du Myélome (IFM) trials: high-dose therapy (HDT) supported with autologous stem cells improves survival, melphalan 200 mg/m(2) is the best preparative regimen, unpurged peripheral blood stem cells (PBSC) are the recommended source of stem cells to...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(01)90014-9
更新日期:2001-07-01 00:00:00
abstract::In this review, we discuss disease-causing alterations of RUNT-related transcription factor 1 (RUNX1), a master regulator of hematopoietic differentiation. Familial platelet disorder with predisposition to myeloid leukemia (FPDMM) typically presents with (1) mild to moderate thrombocytopenia with normal-sized platelet...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2017.04.006
更新日期:2017-04-01 00:00:00
abstract::The molecular causes of hereditary spherocytosis (HS) have been unraveled in the past decade. No frequent defect is found, and nearly every family has a unique mutation. In dominant HS, nonsense and frameshift mutations of ankyrin, band 3, and beta-spectrin predominate. Recessive HS is most often due to compound heter...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2004.01.002
更新日期:2004-04-01 00:00:00
abstract::Iron is a vitally important element in mammalian metabolism because of its unsurpassed versatility as a biologic catalyst. However, when not appropriately shielded or when present in excess, iron plays a key role in the formation of extremely toxic oxygen radicals, which ultimately cause peroxidative damage to vital c...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2002.35638
更新日期:2002-10-01 00:00:00
abstract::Serum vitamin B12 levels are often low in human immunodeficiency virus (HIV)-infected patients. However, only a few patients appear to have actual vitamin B12 deficiency. A low red cell folate level accompanying the low vitamin B12 level makes the presence of vitamin B12 deficiency more likely. Our experience suggests...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::Recombinant factor VIIa (rFVIIa; NovoSeven(R), Novo Nordisk, Bagsvaerd, Denmark) has been used for many years in the successful management of bleeding episodes in patients with hemophilia and inhibitors. More recently, rFVIIa has also shown considerable success as a hemostatic agent in trauma and surgery patients with...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2003.11.019
更新日期:2004-01-01 00:00:00