Abstract:
PURPOSE OF REVIEW:This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). RECENT FINDINGS:The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML. Monoclonal antibodies in AML therapy include naked antibodies against AML surface antigens such as CD33 (e.g. lintuzumab) or CD38 (e.g. daratumumab), antibodies conjugated to toxins in various anti-CD33 (gemtuzumab ozogamicin, SGN33A, IMGN779) and anti-CD123 (SL-401, SGN-CD123A) formulations, and antibodies conjugated to radioactive particles such as I or Ac-labeled anti-CD33 or anti-CD45 antibodies. Additional antigenic targets of interest in AML include CLL1, CD38, CD25, TIM3, FLT3, and others. Approaches to harness the body's own T cells against AML include antibodies that recruit and induce cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as CD33 x CD3 (e.g. AMG 330) or CD123 x CD3 (e.g. flotetuzumab, JNJ-63709178) or antibodies that block immune checkpoint receptors CTLA4 (e.g. ipilimumab) or PD1/PD-L1 (e.g. nivolumab, pembrolizumab, avelumab) on T cells, unleashing the patients' T cells against leukemic cells. SUMMARY:The ongoing trials and well designed correlative interrogation of the immune system in patients treated on such trials will further enhance our understanding and clinical application of immune therapies as single-agent and combination approaches for the treatment of AML.
journal_name
Curr Opin Hematoljournal_title
Current opinion in hematologyauthors
Assi R,Kantarjian H,Ravandi F,Daver Ndoi
10.1097/MOH.0000000000000401subject
Has Abstractpub_date
2018-03-01 00:00:00pages
136-145issue
2eissn
1065-6251issn
1531-7048journal_volume
25pub_type
杂志文章,评审abstract:PURPOSE OF REVIEW:Angioimmunoblastic T cell lymphoma is a complex lymphoproliferative disorder. While recent evidence suggests that the Epstein-Barr virus and B cell disregulation are implicated in the disease's pathogenesis, their mechanistic roles remain largely unknown. The prognosis with traditional chemotherapy ha...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e328186ffbf
更新日期:2007-07-01 00:00:00
abstract:PURPOSE OF REVIEW:Over the last years, long non-coding RNAs (lncRNAs) have emerged as putative regulators of malignant hematopoietic development. Here, we review recent literature on the involvement of lncRNAs in leukemia, including their role in driving or sustaining disease and their potential impact on diagnosis, cl...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000354
更新日期:2017-07-01 00:00:00
abstract::The search for, and discovery of, a physiologic model in which the developmentally regulated switch from fetal to adult globin gene expression could be prevented has resulted in the development of a new class of therapeutic agents, consisting of simple fatty acids, such as butyric acid, for the treatment of the beta-h...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199502020-00002
更新日期:1995-03-01 00:00:00
abstract:PURPOSE OF REVIEW:This article summarizes recent insights into the pathophysiology of immune thrombocytopenic purpura, a disorder in which autoantibodies against cell-specific glycoproteins (GPIIb-IIIa, GPIb-IX and others) accelerate platelet destruction. RECENT FINDINGS:Autoantibodies are produced by a limited number...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3282ba5552
更新日期:2007-09-01 00:00:00
abstract:PURPOSE OF REVIEW:The capacity of lithium to induce neutrophilia and increase circulating CD34(+) cells of marrow origin has long been known. Lithium has been the object of hematological investigations for many years, but no definitive use in hematology has yet emerged. RECENT FINDINGS:We review the evidence that lith...
journal_title:Current opinion in hematology
pub_type: 杂志文章,收录出版,评审
doi:10.1097/MOH.0b013e32834da93b
更新日期:2012-01-01 00:00:00
abstract:PURPOSE OF REVIEW:Early T-cell precursor (ETP) leukaemias have been recently recognized as a form of T-cell acute lymphoblastic leukaemia (T-ALL) with a poor prognosis. The purpose of this review is to outline the most recent advances in the biology, genetics and prognostic significance of this aggressive disease. REC...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283623c61
更新日期:2013-07-01 00:00:00
abstract::Recent studies have improved our understanding of the cytogenesis, biology, and therapy of chronic lymphocytic leukemia (CLL). This review highlights this recent progress reported over the past year. We have improved our understanding of the cytogenetic abnormalities in CLL and soon may see identification of new tumor...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199807000-00003
更新日期:1998-07-01 00:00:00
abstract::Whereas there are general guidelines for acceptable transfusion therapy, optimal transfusion therapy has not been determined for most clinical settings. Recent research has focused on controlled studies of red cell transfusion in specific clinical settings. Better determinations of oxygen delivery and consumption are ...
journal_title:Current opinion in hematology
pub_type: 杂志文章
doi:10.1097/00062752-200111000-00012
更新日期:2001-11-01 00:00:00
abstract:PURPOSE OF REVIEW:Defensins are a major family of antimicrobial peptides expressed predominantly in neutrophils and epithelial cells, and play important roles in innate immune defense against infectious pathogens. Their biological functions in and beyond innate immunity, structure and activity relationships, mechanisms...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000005
更新日期:2014-01-01 00:00:00
abstract::Platelet production is primarily regulated by the thrombopoietic cytokine thrombopoietin (TPO). In most cases thrombopoietin serum levels are determined by the rate of c-mpl receptor-mediated degradation after TPO uptake into platelets and megakaryocytes. The contribution of increased TPO protein synthesis by a transl...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200005000-00003
更新日期:2000-05-01 00:00:00
abstract::Allogeneic barriers to transfusion are caused by differences between those portions of the donor and recipient genomes that define the antigenicity and immune response to the transfused cells. Historically, a blood group antigen was identified when an immune response (alloantibody) was detected by hemagglutination in ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200203000-00012
更新日期:2002-03-01 00:00:00
abstract:PURPOSE OF REVIEW:New discoveries focused on mitochondrial metabolism and gene silencing and their regulation by the sirtuin family of protein deacetylases is stimulating new ideas on how to improve geriatric medicine. Information about sertuins in stem cell biology is scarce. We consider recent information on sirtuin ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283043819
更新日期:2008-07-01 00:00:00
abstract:PURPOSE OF REVIEW:The presence of the Philadelphia chromosome causing the fusion between BCR to ABL1 in B cell precursor acute lymphoblastic leukemias (ALLs) was associated with a particularly bad prognosis, which has been markedly improved with the addition of imatinib to chemotherapy. Recent genomic studies have lead...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000050
更新日期:2014-07-01 00:00:00
abstract:PURPOSE OF REVIEW:The treatment of patients with refractory or relapsed acute myeloid leukemia remains challenging. Management of these patients must take into account patient and leukemia-related factors in order to organize a comprehensive approach to treatment. Many new therapies are under study. RECENT FINDINGS:Ne...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32801684ef
更新日期:2007-03-01 00:00:00
abstract:PURPOSE OF REVIEW:Hematopoietic stem cells are functionally heterogeneous even when isolated as phenotypically homogenous populations. How this heterogeneity is generated is incompletely understood. Several models have been formulated to explain the generation of diversity. All of these assume the existence of a single...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000231421.00407.65
更新日期:2006-07-01 00:00:00
abstract::The advent of better diagnostic tools, molecular techniques, and cytokine therapies have come together at the end of the 20th century to provide an improved outlook for patients with autoimmune neutropenia. Severe chronic neutropenia is no longer idiopathic in most cases, and growth factor therapy can be safely offere...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200105000-00007
更新日期:2001-05-01 00:00:00
abstract::Hairy cell leukemia is an indolent, chronic B-cell lymphoproliferative disorder comprising approximately 2 to 3% of all adult leukemias in the United States. Hairy cells are clonal expansions of mature, activated B-cells. They co-express CD11c, CD19, CD20, CD22, CD25, and CD103. Hairy cells possess clonal immunoglobul...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200307000-00002
更新日期:2003-07-01 00:00:00
abstract::The idea that blood in naturally occurring transmissible spongiform encephalopathies is not infectious has imploded in the face of recent transmissions from the blood of naturally occurring scrapie in sheep and of variant Creutzfeldt-Jakob disease in humans. Although donor exclusion criteria ensure that the number of ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000143393.49202.f0
更新日期:2004-09-01 00:00:00
abstract::The molecular analysis of genetic alterations in acute lymphoblastic leukemia has led to the development of molecular diagnostic techniques that have improved the biologic characterization of newly diagnosed patients. Modern treatment protocols rely on this information to tailor the intensity of therapy to the risk of...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199704040-00003
更新日期:1997-07-01 00:00:00
abstract::Acute chest syndrome (ACS) is the presence of a new pulmonary infiltrate in combination with fever or respiratory symptoms in a patient with sickle cell disease. ACS is the leading cause of death in sickle cell disease, and many patients suffer from multiple, severe episodes. Age has a striking effect on the clinical ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199803000-00002
更新日期:1998-03-01 00:00:00
abstract::The advent of safe and practical means to correct, enhance or protect blood cells at the genetic level offers tantalizing therapeutic perspectives. At present, gene delivery using a replication-defective retrovirus is the most efficient method to stably transduce hematopoietic cells. The successful adaptation of retro...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200011000-00008
更新日期:2000-11-01 00:00:00
abstract:PURPOSE OF REVIEW:To highlight mechanisms that regulate the balance between latent and active von Willebrand factor (VWF), and describe pathological conditions leading to increased levels of active VWF. RECENT FINDINGS:Levels of circulating active VWF are increased in von Willebrand disease type 2B, HELLP syndrome, ma...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3280dce531
更新日期:2007-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Platelet microparticles were identified more than 40 years ago and are the most abundant circulating microparticle subtype. Yet fundamental questions about their formation and role in human disease are just beginning to be understood at the cellular and molecular level. This review will address mechan...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32833e77ee
更新日期:2010-11-01 00:00:00
abstract::During embryogenesis, a pool of pluripotential, self-renewing hematopoietic stem cells is specified from undifferentiated ventral mesoderm. These cells proliferate and differentiate to yield all the peripheral blood lineages. Although the mechanisms involved in the commitment and differentiation of multipotential prog...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199803000-00012
更新日期:1998-03-01 00:00:00
abstract:PURPOSE OF REVIEW:Immune responses to commensal bacteria and resulting chronic inflammation are hallmarks of inflammatory bowel disease. Considerable evidence has accumulated to suggest that innate immune defense mechanisms interact with pro-inflammatory pathways and exacerbate or perhaps even initiate development of i...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200701000-00010
更新日期:2007-01-01 00:00:00
abstract::Neutropenia is often attributed to immunologically mediated injury to mature neutrophils or their precursors. Clinically it is useful to classify immune mediated neutropenias as isoimmune, autoimmune (including some drug-associated neutropenias), and idiopathic (cases possibly with an immune mechanism). Isoimmune neut...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199801000-00006
更新日期:1998-01-01 00:00:00
abstract:PURPOSE OF REVIEW:Therapy-related myelodysplastic syndromes and acute myelogenous leukemia (t-MDS/AML) comprise an increasingly common, poor-risk disease cohort without standard treatment options. This review describes available treatments and recent advances that may influence the clinical management of t-MDS/AML. RE...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32835d82e6
更新日期:2013-03-01 00:00:00
abstract:PURPOSE OF THE REVIEW:Monitoring for residual leukemic burden is an integral part of ongoing evaluation in chronic myeloid leukemia. With high rates of complete cytogenetic response induced by imatinib and other tyrosine kinase inhibitors, exploring refinements in current methods of minimal residual disease monitoring ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3282f42898
更新日期:2008-03-01 00:00:00
abstract:PURPOSE OF REVIEW:Risk assessments for transmission of variant Creutzfeldt-Jakob disease predicted that leukocyte reduction would be inefficient at preventing transmission of the disease by blood transfusion. Nevertheless, approximately 14 years ago, a significant proportion of European countries decided to implement l...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000101
更新日期:2015-01-01 00:00:00
abstract::The bulk of antigens that are presented by major histocompatibility complex (MHC) class I molecules are processed in the cytosol. Therefore, the cellular protein degradation machinery is thought to play a major role in antigen processing. For example, there is clear evidence that the ubiquitin-proteasome pathway, the ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200101000-00003
更新日期:2001-01-01 00:00:00