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 construct in ALL, CAR T-cell therapy has become a mainstay in the ALL treatment algorithm for those with relapsed/refractory disease. Despite the high remission induction rate, with growing experience using CAR T-cell therapy in ALL, a host of barriers to maintaining long-term durable remissions have been identified. Specifically, relapse after, resistance to, or loss of long-term CAR T-cell persistence may all hinder CAR T-cell efficacy. In this review, we provide an overview of the current limitations which inform the design of the next generation of CAR T-cells and discuss advances in CAR T-cell engineering aimed to improve upon outcomes with CAR T-cell-based therapy in ALL.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
Marple AH,Bonifant CL,Shah NNdoi
10.1053/j.seminhematol.2020.07.002subject
Has Abstractpub_date
2020-07-01 00:00:00pages
115-121issue
3eissn
0037-1963issn
1532-8686pii
S0037-1963(20)30020-2journal_volume
57pub_type
杂志文章,评审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::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
doi:10.1053/j.seminhematol.2008.06.006
更新日期:2008-10-01 00:00:00
abstract::Myelodysplastic syndrome (MDS) with deletion 5q (del(5q)) is a distinct clinical and pathological disease subset that is exquisitely sensitive to lenalidomide for the treatment of red blood cell transfusion-dependent anemia. Although lenalidomide has erythropoeitic promoting activity in MDS without del(5q) (non-del(5q...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2017.06.003
更新日期:2017-07-01 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::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::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::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::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 antiviral and antigrowth activity of interferon (IFN) makes this agent a promising approach to cancer therapy. Three tumors that are unusually sensitive to IFN-a are chronic myelogenous leukemia (CML) in the benign phase, hairy-cell leukemia, and the T-cell lymphomas associated with mycosis fungoides. Studies usin...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1988-07-01 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::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::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::It is now well accepted that a subgroup of patients with myelodysplastic syndromes (MDS) can recover from pancytopenia following immunosuppressive treatment (IST). For many years immunosuppression with antilymphocyte antibodies has been a standard treatment approach for patients with severe aplastic anemia (SAA). The ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2012.07.004
更新日期:2012-10-01 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::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
doi:10.1053/j.seminhematol.2011.10.004
更新日期:2012-01-01 00:00:00
abstract::During myeloid differentiation, the pluripotent hematopoietic stem cell passes through several well-defined morphologic stages within the bone marrow. These changes include progressive nuclear segmentation and the acquisition of stage-specific granules. Primary granules appear at the myeloblast stage, and are found in...
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::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::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::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::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::The activation, function, and development of peripheral T lymphocytes are dependent on the ability to signal properly through the surface T-cell antigen receptor (TCR)-CD3 complex. Transmission of such signals requires the activation of specific cytoplasmic protein tyrosine kinases (PTK) associated with the TCR. Recen...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1998-10-01 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::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::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::Stem cell transplantation is a recognized treatment for many hematologic malignancies. Human leukocyte antigen (HLA) testing is a key assessment in the evaluation of potential recipients and selection of the appropriate stem cell donor. Over the past several years, technological advances have moved HLA testing from a ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(01)90052-6
更新日期:2001-04-01 00:00:00
abstract::Though peripheral T-cell lymphoma (PTCL) is an area of significant unmet therapeutic need, a number of new treatment options are available for patients, especially those with relapsed or refractory disease. A plethora of drugs are now in development for PTCL, but drugs that truly target novel disease biology are notic...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2010.01.014
更新日期:2010-04-01 00:00:00
abstract::Even though the overall outcome after allogeneic transplant has improved significantly in the last decades, late infectious diseases are still the most important causes of late morbidity and mortality. Here, impaired immune reconstitution and therapy of chronic graft-versus-host disease (GVHD) represent the major risk...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2011.10.009
更新日期:2012-01-01 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::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 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