Imatinib: a targeted clinical drug development.


: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.


Semin Hematol


Seminars in hematology


Capdeville R,Silberman S




Has Abstract


2003-04-01 00:00:00




2 Suppl 2










  • Improving the safety profile of warfarin.

    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


    authors: Chai SJ,Macik BG

    更新日期:2002-07-01 00:00:00

  • The manufacturing process for recombinant factor IX.

    abstract::Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhan...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Harrison S,Adamson S,Bonam D,Brodeur S,Charlebois T,Clancy B,Costigan R,Drapeau D,Hamilton M,Hanley K,Kelley B,Knight A,Leonard M,McCarthy M,Oakes P,Sterl K,Switzer M,Walsh R,Foster W

    更新日期:1998-04-01 00:00:00

  • Granulocyte aggregation as a manifestation of membrane interactions with complement: possible role in leukocyte margination, microvascular occlusion, and endothelial damage.

    abstract::Activation products of the terminal complement cascade potently affect granulocyte function, inducing, for example, their migration toward (chemotaxis), and adherence to (opsonization), microbes, and stimulating their production of microbicidal oxygen radicals such as superoxide anion, and the like. We present studies...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Craddock PR,Hammerschmidt DE,Moldow CF,Yamada O,Jacob HS

    更新日期:1979-04-01 00:00:00

  • Prognostic relevance of clinical risk factors in mantle cell lymphoma.

    abstract::Mantle cell lymphoma (MCL) has only recently been recognized as a separate biologically defined lymphoma entity. Due to its low incidence, many reports on clinical prognostic factors are limited by small patient numbers. The MCL International Prognostic Index (MIPI) was developed using data of more than 400 patients t...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Hoster E

    更新日期:2011-07-01 00:00:00

  • Myelodysplastic syndromes: From pathogenesis and prognosis to treatment.

    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


    authors: Fenaux P

    更新日期:2004-04-01 00:00:00

  • Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment.

    abstract::This report suggests modest changes in the criteria used for the diagnosis of ET and allows tentative recommendations concerning therapy. As outlined in Table I, we believe that absent stainable marrow iron does not necessarily indicate iron deficiency in these patients and that the serum ferritin and RBC mean corpusc...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Murphy S,Peterson P,Iland H,Laszlo J

    更新日期:1997-01-01 00:00:00

  • Epidemiology of anemia in older adults.

    abstract::Anemia is a common, multifactorial condition among older adults. The World Health Organization (WHO) definition of anemia (hemoglobin concentration <12 g/dL in women and <13 g/dL in men) is most often used in epidemiologic studies of older adults. More than 10% of community-dwelling adults age 65 years and older has W...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Patel KV

    更新日期:2008-10-01 00:00:00

  • CD4+CD25+ regulatory T cells and graft-versus-host disease.

    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


    authors: Hoffmann P,Edinger M

    更新日期:2006-01-01 00:00:00

  • Analysis of the molecular genetics of acute promyelocytic leukemia in mouse models.

    abstract::Acute promyelocytic leukemia (APL) is characterized by reciprocal chromosomal translocations that always Involve the retinoic acid receptor-alpha (RARalpha) gene on chromosome 17. RARalpha variably fuses to the PML, PLZF, NPM, NuMA, and STAT 5b genes (X genes), leading to the generation of X-RARalpha and RARalpha-X fu...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Rego EM,Pandolfi PP

    更新日期:2001-01-01 00:00:00

  • Comprehensive characterization of circulating and bone marrow-derived multiple myeloma cells at minimal residual disease.

    abstract::The presence or absence of minimal residual disease (MRD) in patients with multiple myeloma (MM) has emerged as a useful marker to determine the depth of remission. MRD negativity as an endpoint has been shown to be associated with improved progression-free survival in many studies. MRD detection is therefore part of ...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Waldschmidt JM,Anand P,Knoechel B,Lohr JG

    更新日期:2018-01-01 00:00:00

  • Mantle-cell lymphoma.

    abstract::Mantle-cell lymphoma (MCL) is a lymphoproliferative disorder derived from a subset of naive pregerminal center cells characterized by a nodular or diffuse proliferation of atypical lymphoid cells with a monoclonal B-cell phenotype and coexpression of CD5. Two cytologic variants have been identified, typical and blasti...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Campo E,Raffeld M,Jaffe ES

    更新日期:1999-04-01 00:00:00

  • Rituximab in indolent lymphomas.

    abstract::Indolent non-Hodgkin lymphoma (NHL) comprises a group of incurable, generally slow-growing lymphomas highly responsive to initial therapy, with a relapsing and progressive course. Rituximab, an anti-CD20 antibody, has had a large impact on the treatment of indolent NHL. Its effectiveness as a single agent and in conju...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Sousou T,Friedberg J

    更新日期:2010-04-01 00:00:00

  • Screening for hemochromatosis: phenotype versus genotype.

    abstract::Hereditary hemochromatosis is one of the most common inherited disorders among Caucasians of European ancestry. Malregulation of iron absorption from the duodenum eventually leads to iron overload. Although the time required to become iron loaded is variable, it is clear that most homozygotes will eventually become sy...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Edwards CQ,Griffen LM,Ajioka RS,Kushner JP

    更新日期:1998-01-01 00:00:00

  • Transplant strategies for idiopathic myelofibrosis.

    abstract::Idiopathic myelofibrosis (IMF) is a clonal stem cell disorder and is one of the four major myeloproliferative disorders, which include essential thrombocythemia (ET), polycythemia vera (PV), and chronic myelogenous leukemia (CML). Patients may be asymptomatic at the early stages, but later progress to marrow fibrosis,...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: McCarty JM

    更新日期:2004-04-01 00:00:00

  • Quality of life, social challenges, and psychosocial support for long-term survivors after allogeneic hematopoietic stem-cell transplantation.

    abstract::Over the last two decades quality of life (QoL) and the social challenges of allogeneic hematopoietic stem cell transplant (allo-HSCT) survivors have been emerging as subjects of extensive research and are now considered as very important aspects in the pretransplant evaluation and management of allo-HSCT recipients. ...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Norkin M,Hsu JW,Wingard JR

    更新日期:2012-01-01 00:00:00

  • Pharmacologic approaches to reversing multidrug resistance.

    abstract::The rationale for modulation of multidrug resistance (MDR) by inhibitors of the multidrug transporter, P-glycoprotein (P-gp) includes the following: (1) P-gp is expressed by human cancers, either at diagnosis or after failure of chemotherapy; (2) P-gp expression at diagnosis has been associated with a poor prognosis i...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Sikic BI

    更新日期:1997-10-01 00:00:00

  • Myelodysplastic syndrome in children and adolescents.

    abstract::Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and subsequent frequent development of acute myeloid leukemia (AML). In children and adolescents, MDS are uncommon disorders, accounting for less than 5% of hematopoietic malignancy, with great heterogeneity in presentation...

    journal_title:Seminars in hematology

    pub_type: 杂志文章


    authors: Niemeyer CM,Baumann I

    更新日期:2008-01-01 00:00:00

  • Risks and benefits of erythropoiesis-stimulating agents in cancer management.

    abstract::Anemia is frequently diagnosed in patients with cancer and its treatment is an important clinical problem. The deficiency in red blood cells (RBCs) can be a debilitating problem, and anemia correlates with poor performance status, deteriorates quality of life, and may negatively influence the prognosis of cancer patie...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Beutel G,Ganser A

    更新日期:2007-07-01 00:00:00

  • Improving CAR T-cells: The next generation.

    abstract::The introduction of chimeric antigen receptor (CAR) T-cell therapy in acute lymphoblastic leukemia (ALL) has dramatically altered the landscape of treatment options available to children and adults with ALL. With complete remission induction rates exceeding 70% in most trials and FDA approval of one CD19 CAR T-cell co...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Marple AH,Bonifant CL,Shah NN

    更新日期:2020-07-01 00:00:00

  • The pathogenesis of chronic immune thrombocytopenic purpura.

    abstract::Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which the patient's immune system reacts with a platelet autoantigen(s) resulting in thrombocytopenia due to immune-mediated platelet destruction and/or suppression of platelet production. Platelet membrane proteins, for reasons that are unclea...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: McMillan R

    更新日期:2007-10-01 00:00:00

  • Somatic characterization of pediatric acute myeloid leukemia using next-generation sequencing.

    abstract::Acute myeloid leukemia (AML) is a complex and heterogeneous disease with distinct age-associated genomic and epigenomic alterations. A large number of somatic karyotypic and molecular alterations have been identified in AML to date; however, very few predict outcome or identify potential therapeutic targets. Here we d...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Schuback HL,Arceci RJ,Meshinchi S

    更新日期:2013-10-01 00:00:00

  • Future strategies toward the cure of indolent B-cell malignancies. Immune recognition and antiself.

    abstract::Tumor cells from patients with B-cell malignancies exhibit a number of immunophenotypic characteristics that may be responsible for their survival. It has been shown, for example, that down-modulation of CD154 (CD40 ligand), which allows B cells to respond to T cells, may account for some of the immune defects of thes...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Nadler LM

    更新日期:1999-10-01 00:00:00

  • Bayesian interpretation and analysis of research results.

    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


    authors: Greenland S

    更新日期:2008-07-01 00:00:00

  • The potential role of new therapies in deep-vein thrombosis prophylaxis.

    abstract::The value of prophylaxis against venous thromboembolism (VTE) is increasingly accepted in most surgical specialties, although the potential reduction in fatal pulmonary embolism has recently been questioned. The burden of VTE in hospital patients nevertheless remains high, partly attributable to underuse of thrombopro...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Wille-Jørgensen P

    更新日期:2001-04-01 00:00:00

  • Surface and cytoskeletal events regulating leukocyte membrane topography.

    abstract::The experiments reviewed here establish that surface components and surface functions can assume predictable, asymmetric patterns within the continuous plasma membranes of mammalian leukocytes. Recent biophysical and morphological studies show that receptor redistribution can occur very rapidly and that a unique geome...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Oliver JM,Berlin RD

    更新日期:1983-10-01 00:00:00

  • Laboratory tests for heparin-induced thrombocytopenia: a multicenter study.

    abstract::A multicenter clinical trial of the thrombin inhibitor argatroban (Novastan; Texas Biotechnology, Houston, TX; Smith-Kline Beecham Pharmaceuticals, Philadelphia, PA) was recently conducted in patients with heparin-induced thrombocytopenia (HIT) and HIT that had progressed to thrombosis (HITTS). In patients defined by ...

    journal_title:Seminars in hematology

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Walenga JM,Jeske WP,Wood JJ,Ahmad S,Lewis BE,Bakhos M

    更新日期:1999-01-01 00:00:00

  • Who is the best donor for haploidentical stem cell transplantation?

    abstract::Recent advances in haploidentical stem cell transplantation have enabled the use of human leukocyte antigen-half matched related donors for allogeneic stem cell transplantation and helped overcome one of the most important limitation in transplantation, which is donor availability, especially for the non-Caucasian pop...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Kongtim P,Ciurea SO

    更新日期:2019-07-01 00:00:00

  • Treatment of hemangiomatosis with recombinant interferon alfa.

    abstract::Hemangiomas and lymphangiomas are two main types of angiomatous disease that occur most commonly in infancy and childhood. Most hemangiomas resolve spontaneously, but some endanger vital structures such as the lung, as in pulmonary hemangiomatosis, a rare and universally fatal disease. Occasionally, hemangiomatous les...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: White CW

    更新日期:1990-07-01 00:00:00

  • Perspectives on the future of chronic myeloid leukemia treatment.

    abstract::Chronic myeloid leukemia (CML) is probably the best understood human malignancy at the molecular level, but among the hardest to explain to patients concerning appropriate treatment options. At present, we do not know the long-term outcome of promising new therapies such as the tyrosine kinase inhibitor imatinib mesyl...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Appelbaum FR

    更新日期:2001-07-01 00:00:00

  • The impact of epoetin alfa on quality of life during cancer chemotherapy: a fresh look at an old problem.

    abstract::Untreated anemia is common in cancer patients. Previous studies have demonstrated that both the existence of cancer and treatment with chemotherapy can suppress the normal endogenous erythropoietic response to anemia, making some cancer patients transfusion cadidates. In placebo-controlled phase III studies, administr...

    journal_title:Seminars in hematology

    pub_type: 临床试验,杂志文章


    authors: Glaspy J

    更新日期:1997-07-01 00:00:00