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 potent chemicals to form immunotoxins or combined with various radionuclides. Encouraging results have been obtained in all three settings. The CD33 antigen is expressed by most early myeloid cells and by more than 90% of cases of AML but is not present on the hematopoietic stem cell. Initial in vivo studies with an unmodified murine anti-CD33 antibody in patients with AML demonstrated that the antibody quickly bound to leukemia cells and that the antigen-antibody complex rapidly internalized following cell binding. However, when administered to patients with overt leukemia, unmodified antibody resulted in only brief decreases in peripheral blast counts, not in sustained response. A number of CD33-based immunotoxins have also been studied, including a calicheamicin conjugate, CMA-676. In a phase I dose-escalation study of patients with refractory AML, CMA-676 was well tolerated with the only consistent toxicities being the development of fevers and chills several hours after administration and the subsequent development of temporary pancytopenia. A phase III study has been performed involving patients with AML in first relapse. An interim analysis of the first 23 patients found that in 10, treatment with CMA-676 resulted in elimination of blasts from peripheral blood and marrow. This was achieved with far less toxicity than seen with standard chemotherapy. Radiolabeled antibodies have been explored as a stand-alone treatment or in the context of bone marrow transplantation. In an effort to avoid toxicities to normal stem cells residing alongside leukemic cells in the marrow, studies have been performed to explore the use of 231Bi conjugated to an anti-CD33 monoclonal antibody. The short path length of this alpha-emitter could theoretically allow killing of the targeted leukemic cell without damage to normal neighbors. Of 12 patients with recurrent AML who received this drug, eight had reductions in marrow and peripheral blast counts. Complete remissions (CRs) have not been observed to date. Another set of studies focused on the use of radiolabeled antibodies to deliver radiation specifically to sites of leukemia as part of a transplant preparative regimen. In a phase I clinical trial, 131I-labeled anti-CD45 antibody delivered at least threefold more radiotherapy to spleen and marrow than any other organ. In a phase II trial, among 25 AML patients in first remission, 22 are alive and in remission for periods up to 6 years.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
Appelbaum FRsubject
Has Abstractpub_date
1999-10-01 00:00:00pages
2-8issue
4 Suppl 6eissn
0037-1963issn
1532-8686journal_volume
36pub_type
杂志文章,评审abstract::By definition, myeloproliferative disorders (MPDs) are caused by an acquired somatic mutation of a hematopoietic progenitor/stem cell and have sporadic occurrence. However, well-documented families exist with first-degree relatives acquiring one or several MPDs. It is reasonable to assume that the germ-line mutation(s...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2005.08.002
更新日期:2005-10-01 00:00:00
abstract::Over the past 2 decades, treatment of Hodgkin's disease has evolved considerably through innovations in the management of various stages. The impact of various treatments on the 5-, 10-, and 15-year results is being balanced against delayed morbidity, such as organ damage and second malignancies, produced by the inten...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1988-04-01 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 farnesyltransferase inhibitors (FTIs) have been shown in early clinical trials to elicit antitumor actions in a broad range of solid and hematologic malignancies. The mechanism of FTI action involves blockade of farnesyltransferase, an enzyme implicated in multiple cell-signaling pathways involved in proliferation...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2002.35984
更新日期:2002-07-01 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::Endogenous thrombopoietin (TPO) stimulates platelet production in nonhuman primates by inducing dose-dependent megakaryocyte development from early marrow hematopoietic progenitors and subsequent proliferation and endoreduplication. In nonhuman primates, recombinant human TPO, nonpegylated or pegylated rHu megakaryocy...
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::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
doi:10.1053/j.seminhematol.2011.06.001
更新日期:2011-07-01 00:00:00
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
doi:10.1053/j.seminhematol.2007.04.004
更新日期:2007-07-01 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::The B-cell receptor (BCR) is of critical importance for normal B cells and for the majority of B-cell malignancies, especially chronic lymphocytic leukemia (CLL). The two major subsets of CLL are biologically distinct, being derived from B cells at different stages of differentiation and carrying unmutated (U-CLL) or ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2014.05.003
更新日期:2014-07-01 00:00:00
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
doi:10.1053/j.seminhematol.2018.02.010
更新日期:2018-01-01 00:00:00
abstract::Most of the major advances in thrombosis research have occurred in the last 50 years, reflecting progress in biomedical sciences and clinical trials methodology. Improved understanding of the mechanisms of thrombogenesis has led to the discovery of a plethora of new antithrombotic agents that target many of the key st...
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::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::Although often overlooked, the life of the patient with severe hemophilia is characterized by both intermittent and chronic pain. Bleeds into joints and muscles cause extensive pressure on sensory nerves and, following recurrent bleeds, joint destruction, and synovial reaction is accompanied by constant pains that are...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2005.11.024
更新日期:2006-01-01 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::Traditionally, acute myeloid leukemia (AML) has been diagnosed and classified based on the morphologic and cytochemical criteria of the French-American-British (FAB) classification system. However, more recent studies have demonstrated that the cytogenetic and molecular genetic abnormalities consistently associated wi...
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::An immune hemolytic anemia occurs in a few patients in whom the concentration of antibody on the red cell is below the level for detection by the usual antiglobulin test. Clinically, these patients are identical to patients with warm type Coombs-positive hemolytic anemia, except for the quantity of antibody on the cel...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
abstract::Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA)-matched sibling is the treatment of choice in children and young adults with severe aplastic anemia (SAA). However, because only 30% of patients have a suitable donor, more aggressive nontransplant immunosuppressive regimens have been used, with re...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(00)90029-5
更新日期:2000-01-01 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::Cyclic neutropenia is a rare hematologic disorder, characterized by repetitive episodes of fever, mouth ulcers, and infections attributable to recurrent severe neutropenia. Fluctuations in blood cells are due to oscillatory production of cells by the bone marrow. Recent genetic, molecular, and cellular studies have sh...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2002.31917
更新日期:2002-04-01 00:00:00
abstract::Acute myeloid leukemia (AML) is a heterogeneous disease characterized by multiple genetic and epigenetic alterations. The major causes of treatment failure remain disease relapse and treatment toxicity. However, major advances in biological determinants of disease relapse, development of targeted molecules, improvemen...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2015.03.001
更新日期:2015-07-01 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::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::In early studies, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been found to reduce the depth and duration of granulocytopenia in the settings of cancer chemotherapy and autologous bone marrow transplantation. In patients with myelodysplastic syndrome or aplastic anemia. GM-CSF has p...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1990-07-01 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::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::Anemia is frequent and significantly adds to the morbidity of cancer patients, and has been associated with decreased quality of life (QOL). Three open-label community-based studies of epoetin alfa in cancer-related anemia (two using three-times-weekly dosing and one using once-weekly dosing) in more than 7,000 patien...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(00)90062-3
更新日期:2000-10-01 00:00:00
abstract::Familial thrombosis has long been considered as an autosomal dominant trait, caused by a dominant gene defect with a reduced penetrance for the disease. Recently, this view has changed and today familial thrombophilia is considered as a complex genetic disorder caused by the segregation of two or more gene defects (kn...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1997-07-01 00:00:00
abstract::The use of combination chemotherapy has been successful in treating advanced or widespread Hodgkin's disease (HD). For patients with relapsed disease, the long-term prognosis is much poorer, despite the good rate of reinduction into a second or further remission using conventional treatments. The majority of such pati...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-07-01 00:00:00
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
doi:
更新日期:1983-10-01 00:00:00