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 initial dose of 5 mg/m2/d for 3 days with an increment of 2.5 mg/m2/d to 15 mg/m2/d for 3 days. The dose-limiting toxicities (DLTs) were thought to be stomatitis and anorexia. The maximum tolerated dose (MTD) was determined to be 15 mg/m2/d for 3 days (45 mg/m2 per course). Bone marrow toxicity was significant when greater than 10 mg/m2/d of IDA was given. When IDA was administered at this dosage or higher, there were three CRs and four partial responses, with an overall response rate of 26.9% in 26 assessable patients. It is recommended that a phase II study be undertaken at an IDA dosage of 10 to 15 mg/m2/d for 3 consecutive days in the treatment of acute leukemia. Twenty-one of 32 patients were also studied for the pharmacokinetics of IDA. The terminal half-life (t1/2) values for IDA were 6.4 to 15.1 hours in plasma and 8.09 to 16.34 hours in blood cells. The t1/2 values for idarubicinol were much longer: 43.46 to 51.01 hours in plasma and 36.61 to 54.70 hours in blood cells. Concentrations of idarubicinol in plasma and blood cells exceeded those of IDA 2 to 4 hours after the start of treatment and remained elevated for a long time. The area under the curve (AUC) of idarubicinol in plasma was 5.16 to 8.36 times higher than that of IDA, and the AUC of idarubicinol in blood cells was 2.05 to 4.57 times higher than that of IDA. The AUCs of both IDA and idarubicinol increased dose-dependently over the dosage range of 5 to 15 mg/m2/d. When two-compartment multiple-dose models were used, plasma t1/2 alpha and t1/2 beta values of IDA were 0.25 +/- 0.13 and 9.4 +/- 3.4 hours, respectively. The steady-state volume of distribution (Vdss) was 934.9 +/- 370.7 L/m2, and the plasma clearance was 82.3 +/- 29.7 L/h/m2. The urinary excretion of IDA and its metabolite was low. The mean cumulative urinary recovery rates were 2.04% for IDA and 11.53% for idarubicinol up to 7 days.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
Tamura Ksubject
Has Abstractpub_date
1996-10-01 00:00:00pages
2-11issue
4 Suppl 3eissn
0037-1963issn
1532-8686journal_volume
33pub_type
临床试验,杂志文章,评审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 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
doi：10.1053/j.seminhematol.2007.11.002
更新日期：2007-10-01 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：:Patients with acute myeloid leukemia (AML) who achieve complete remission after induction therapy require post remission therapy (PRT) in order to remain disease free. The role of autologous hematopoietic cell transplantation (autoHCT) in the PRT setting is controversial and is largely based on older trials that were ...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2019.01.001
更新日期：2019-04-01 00:00:00
abstract：:Mechanisms that support migration of leukocytes have been studied extensively in vitro. The adhesion of neutrophils under conditions of flow at venous shear rates primarily involves members of the selectin family. E-selectin is upregulated by cytokine stimulation of endothelial cells (ECs); P-selectin is upregulated b...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1993-10-01 00:00:00
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
doi：10.1053/j.seminhematol.2010.01.003
更新日期：2010-04-01 00:00:00
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
doi：10.1053/j.seminhematol.2013.09.003
更新日期：2013-10-01 00:00:00
abstract：:Because optimal management of iron chelation therapy in patients with sickle cell disease and transfusional iron overload requires accurate determination of the magnitude of iron excess, a variety of techniques for evaluating iron overload are under development, including measurement of serum ferritin iron levels, x-r...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(01)90059-9
更新日期：2001-01-01 00:00:00
abstract：:Cytogenetic data suggest that acute myeloid leukemia (AML) develops through a process of branching evolution, especially during relapse and progression. Recent genomic data from AML cases using digital sequencing, temporal comparisons, xenograft cloning, and single-cell analysis indicate that most, if not all, AML cas...
journal_title：Seminars in hematology
pub_type： 杂志文章
doi：10.1053/j.seminhematol.2014.08.004
更新日期：2014-10-01 00:00:00
abstract：:Our advanced knowledge of coagulation has led to the synthesis of novel procoagulant substances, such as recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). Similarly, in-depth understanding of the interaction between anticoagulant proteins and their natural inhibitors has led to th...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2005.11.023
更新日期：2006-01-01 00:00:00
abstract：:Myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPN are characterized by clonal proliferation of myeloid progenitors leading to erythrocytosis, thrombocytosis, or leukocytosis, and risk of hemorrhagic and thrombotic events, as well as ...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2018.04.005
更新日期：2018-10-01 00:00:00
abstract：:Severe neutropenia renders patients susceptible to life-threatening bacterial and fungal infections. Despite improvements in supportive care and antimicrobial therapy, morbidity and mortality remains significant. Since the 1960s, granulocyte transfusions have been used to either treat or prevent serious infections in ...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2019.11.002
更新日期：2019-10-01 00:00:00
abstract：:The risk of postoperative venous thromboembolism (VTE) is dependent on the type of surgical procedure and specific characteristics of the patient. Patients with intrinsic factors placing them at higher risk of VTE remain at high risk, even if the procedural risk is low. The identification of factors such as age, obesi...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(00)90094-5
更新日期：2000-07-01 00:00:00
abstract：:Management of patients with beta-thalassemia is based on adequate, safe blood transfusions (free of transfusion-transmitted diseases) and prevention of iron overload. Iron overload causes multiple endocrinopathies, contributes to osteoporosis, and is the cause of cardiac disease. Cardiac disease, secondary to iron dam...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(01)90029-0
更新日期：2001-10-01 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：:The stem cell origination of the clonal process in chronic myeloproliferative disorders (CMPDs) is well established. In chronic myelogenous leukemia (CML), the primary genetic process has been characterized. However, current information regarding the mechanisms of phenotypic diversity among the CMPD and the downstream...
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：:Thrombopoietin (TPO) regulates thrombopoiesis through activation of TPO receptors on the megakaryocyte cell surface, resulting in increased platelet production. The TPO receptor agonists are novel treatments for patients with chronic ITP aimed at increasing platelet production through interactions with the TPO recepto...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2013.03.005
更新日期：2013-01-01 00:00:00
abstract：:5-Aza-2'-deoxycytidine (decitabine; Dacogen, MGI Pharma, Inc, Bloomington, MN) is a cytidine analog that inhibits DNA methyltransferases resulting in loss of DNA methylation with subsequent gene re-expression. This compound was first synthesized over 40 years ago and since that time much information has been learned r...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2005.05.006
更新日期：2005-07-01 00:00:00
abstract：:While the prevalence of iron deficiency has remained relatively constant, there has been continuing refinement in its laboratory recognition, especially with the recent introduction of serum ferritin and FEP measurements. It is helpful to classify iron deficiency into three stages. Storage iron depletion is identified...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1982-01-01 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：: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
doi：
更新日期：1997-07-01 00:00:00
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
doi：
更新日期：1998-04-01 00:00:00
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
doi：
更新日期：1997-01-01 00:00:00
abstract：:Bendamustine is a bifunctional mechlorethamine derivative that shares similarities to other alkylators; however, the presence of a benzimidazole ring may confer "nucleoside-like" properties and may allow the stabilization of the molecule leading to longer lasting DNA damage. Though bendamustine has demonstrated promis...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2011.03.005
更新日期：2011-04-01 00:00:00
abstract：:Both thalidomide and intermittent high-dose dexamethasone are agents with established activity against multiple myeloma. We summarized our experience with thalidomide alone, and then in combination with dexamethasone, for groups of patients with myeloma resistant or relapsing despite standard treatments. Criteria of r...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2003.09.006
更新日期：2003-10-01 00:00:00
abstract：:These two issues of the Seminars in Hematology will provide the physician the necessary knowledge to help make sense of this somewhat confusing array of diseases. The subdivisions of MDS reflect the precision of our techniques of dissection, with morphological and histochemical analyses forming the foundation to ident...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1996-04-01 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：: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
doi：
更新日期：1997-10-01 00:00:00
abstract：:The cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine (COP-BLAM) programs of combination chemotherapy were administered to patients with advanced diffuse large cell lymphoma. The original COP-BLAM programs were designed to deliver intense multidrug therapy maximizing tumor kill. COP-BLAM ...
journal_title：Seminars in hematology
pub_type： 杂志文章
doi：
更新日期：1988-04-01 00:00:00
abstract：:The virome has been recently studied in hematology and mostly in the setting of allogeneic hematopoietic stem cell transplantation. However, in hematology (as in the setting of nonhematological disorders) the study of the microbiome (that indeed includes the virome) is a growing field. The overall field is moving beyo...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2020.05.001
更新日期：2020-01-01 00:00:00
