Abstract:
:While cure rates of over 80% are achieved in contemporary pediatric acute lymphoblastic leukemia (ALL) protocols, most adults with ALL succumb to their disease, and little progress has been made in the treatment of refractory and relapsed ALL. Moreover, the burden of therapy is high in a significant number of newly diagnosed patients, and in all those with relapse. Early response to therapy measured by minimal residual disease evaluation has proven the single most important prognostic factor and is increasingly used in risk stratification. However, as the benefit from intensification of frontline therapy becomes limiting, it becomes increasingly challenging to rescue patients who fail on contemporary risk-adapted protocols. New therapeutic strategies are needed, not only in salvage regimens but also in frontline protocols for patients who are at high risk of relapse. Current novel approaches include new formulations of existing chemotherapeutic agents, new antimetabolites and nucleoside analogs, monoclonal antibodies against leukemic-associated antigens, cellular immunotherapy, and molecular therapeutics. Some have already been adopted into standard regimens, while others remain in early stages of development. This review summarizes the current status of these novel therapies as they get integrated into ALL regimens.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
Jeha Sdoi
10.1053/j.seminhematol.2008.09.009subject
Has Abstractpub_date
2009-01-01 00:00:00pages
76-88issue
1eissn
0037-1963issn
1532-8686pii
S0037-1963(08)00167-4journal_volume
46pub_type
杂志文章,评审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
doi:
更新日期:1999-01-01 00:00:00
abstract::Trauma is rapidly replacing stroke and cardiovascular disease as a leading cause of death in Western countries such as the United States, and almost a third (30%) of trauma deaths are due to blood loss. Although the new intervention strategies that have been developed and adopted by emergency care staff have reduced t...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2003.11.009
更新日期:2004-01-01 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::There are now more than 25 million volunteer donors registered worldwide for patients in need of a life-saving hematopoietic cell transplant to cure blood disorders. Although a human leukocyte antigen (HLA)-matched donor remains the preferred stem cell source for transplantation, the use of a donor with limited HLA mi...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2016.07.003
更新日期:2016-10-01 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::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::Various pathways lead to the development of venous thrombosis. Risk factors are common and can be genetic or acquired. Since the identification of factor V Leiden and prothrombin 20210 G-->A, the field of genetic epidemiology has developed rapidly and many new genetic variants have been described in the past decade. H...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2007.01.007
更新日期:2007-04-01 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
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
doi:10.1053/j.seminhematol.2020.07.002
更新日期:2020-07-01 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::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::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::Anemia of chronic disease (ACD) or inflammation may be secondary to infections, autoimmune disorders, chronic renal failure, or malignancies. It is characterized by an immune activation with an increase in inflammatory cytokines and resultant increase in hepcidin levels. In addition, inappropriate erythropoietin level...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2013.06.006
更新日期:2013-07-01 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::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
doi:
更新日期:1998-01-01 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 delineation of specific erythrocyte glycolytic enzyme defects during the past three decades has clarified hitherto unexplained hereditary hemolytic syndromes. The glycolytic enzymopathies have proven to be important, not as a public health problem, but because the investigation of these experimental models of natu...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1990-04-01 00:00:00
abstract::Von Willebrand disease (VWD) is the most commonly inherited bleeding disorder, caused by inheritance of a quantitative or qualitative abnormality of von Willebrand factor (VWF). While the majority of patients with VWD are successfully treated with adjunctive therapies or with the synthetic vasopressin analog desmopres...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(01)90131-3
更新日期:2001-10-01 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::Hodgkin Lymphoma (HL) is a lymphoproliferative disorder of B cells that commonly has a favorable prognosis when treated with either combination chemotherapy and radiation therapy, or chemotherapy alone. However, the prognosis for patients who relapse, or have evidence for refractory disease, is poor and new treatments...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2016.05.011
更新日期:2016-07-01 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::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::The immunomodulatory drug (IMiD) lenalidomide is a more potent immunomodulator than thalidomide with respect to its effects on cytokine modulation and increased T-cell proliferation. Of all the IMiDs, clinical trial data are most mature for lenalidomide. In phase I studies, dose-limiting toxicities of lenalidomide wer...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2005.10.004
更新日期:2005-10-01 00:00:00
abstract::Recombinant activated factor VII (rFVIIa) is being increasingly used to treat bleeding associated with a variety of non-hemophilic coagulopathic indications, and its mechanism of action in these areas is under active investigation. Numerous studies have shown that FVIIa binds with low affinity to activated platelets; ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2008.03.013
更新日期:2008-04-01 00:00:00
abstract::High-dose chemoradiotherapy with allogeneic bone marrow or peripheral blood stem cell transplantation (SCT) is a potentially curative treatment for advanced or poor-prognosis hematological malignancies. This procedure was initially considered as a means to deliver supralethal doses of chemotherapy and radiation for th...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2002.30909
更新日期:2002-01-01 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 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::Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2008.12.005
更新日期:2009-01-01 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::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