Abstract:
:The myeloproliferative neoplasms (MPNs) encompass a heterogenous set of diseases that have variable survival, but in the setting of treatment refractory and progressive disease, prognosis has been characteristically poor. JAK inhibition with ruxolitinib or fedratinib therapy has become the first line treatment for symptomatic or intermediate to high risk myelofibrosis. However, after three years of ruxolitinib therapy, approximately half of all patients with myelofibrosis will likely have stopped treatment. JAK inhibition failure represents a mixture of etiologies, including drug intolerance, suboptimal dosing, drug resistance, or progression of disease. JAK inhibition failure and accelerated/blast phase have now become the primary clinical challenges in the treatment of myelofibrosis and high risk polycythemia vera, and no phase III trials or clear treatment guidelines exist to guide management strategies in this setting. On the other hand, this represents an exciting time in treatment of JAK inhibitor failure and accelerated phase MPNs due to the advent of recently approved drugs as well as new targeted agents currently under investigation. In this article, we review the management options for these challenging clinical scenarios. We discuss the options for JAK inhibitor dose optimization and overcoming resistance by utilizing combinations of JAK inhibition, primarily ruxolitinib, with alternative commercially available therapies. For patients who have progressed, we discuss recent data regarding targeted therapy options approved for AML that represent potentially efficacious options in the progressive MPN setting. We also discuss the new clinical agents under development in MF and accelerated MPNs that may offer new therapeutic options in the years to come.
journal_name
Blood Revjournal_title
Blood reviewsauthors
Scherber RM,Mesa RAdoi
10.1016/j.blre.2020.100716subject
Has Abstractpub_date
2020-07-01 00:00:00pages
100716eissn
0268-960Xissn
1532-1681pii
S0268-960X(20)30066-7journal_volume
42pub_type
杂志文章,评审相关文献
BLOOD REVIEWS文献大全abstract::Gaucher disease was first described by Philippe Gaucher in his 1882 medical thesis. Gaucher's original concept was of an unusual epithelioma of the spleen. By the early 1900s, Mandelbaum recognized the systemic nature of the disease. Several children with Gaucher disease were described at the turn of the century, but ...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/s0268-960x(98)90023-6
更新日期:1998-06-01 00:00:00
abstract::Invasive fungal infections are significant causes of morbidity and mortality in patients with hematological malignancies. Patients with acute myeloid leukemia and those who have undergone allogeneic hematopoietic stem cell transplantation are at especially high risk. Various fungal agents are responsible for this comp...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2009.11.003
更新日期:2010-03-01 00:00:00
abstract::Universal leucocyte depletion has been implemented in the UK and several other European countries as a precautionary measure against the potential risk of transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Leucocyte depletion had previously only been recommended for a relatively small proportion o...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1054/blre.2000.0130
更新日期:2000-09-01 00:00:00
abstract::Most acute myeloid leukemia (AML) patients will be aged more than 65 years. Chronological aging is accompanied by decreasing stem cell and solid organ reserve as well as an increased incidence of medical comorbidity. For the older patient with AML, these patient-specific factors are compounded by an association with c...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2019.100639
更新日期:2020-03-01 00:00:00
abstract::Immune checkpoint inhibitors (ICI) have yielded mixed but largely underwhelming results in clinical trials in patients with acute myeloid leukemia and myelodysplastic syndromes to date. However, increasing understanding of the immunologic landscape, potential biomarkers for benefits, and mechanisms of resistance, as w...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2020.100709
更新日期:2020-05-23 00:00:00
abstract::Erythropoiesis is a dynamic process regulated at multiple levels to balance proliferation, differentiation and survival of erythroid progenitors. Ineffective erythropoiesis is a key feature of various diseases, including β-thalassemia. The pathogenic mechanisms leading to ineffective erythropoiesis are complex and sti...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2017.10.001
更新日期:2018-03-01 00:00:00
abstract::The majority of aggressive lymphomas is characterized by an up regulated glycolytic activity, which enables the visualization by F-18 FDG-PET/CT. One-stop hybrid FDG-PET/CT combines the functional and morphologic information, outperforming both, CT and FDG-PET as separate imaging modalities. This has resulted in sever...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2016.02.003
更新日期:2016-07-01 00:00:00
abstract::Thrombopoietin (TPO) is the key cytokine involved in thrombopoiesis, and is the endogenous ligand for the thrombopoietin receptor that is expressed on the surface of platelets, megakaryocytes, and megakaryocytic precursors. First-generation thrombopoietic agents were recombinant forms of human TPO, and their developme...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2010.04.002
更新日期:2010-07-01 00:00:00
abstract::Stem cell factor is an essential haemopoietic progenitor cell growth factor with proliferative and anti-apoptotic functions. Molecular biologists have now dissected some of the various pathways through which this cytokine signals to the nucleus. At the same time, new molecules have become available which can inhibit S...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1054/blre.2001.0167
更新日期:2001-12-01 00:00:00
abstract::Congenital platelet disorders include thrombocytopathies and thrombocytopenias, which often occur in association. Thrombocytopathies constitute a model for exploring platelet physiology at the molecular level: adhesion, activation, release phenomena, aggregation. Further advances in understanding thrombocytopenias now...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/0268-960x(88)90004-5
更新日期:1988-03-01 00:00:00
abstract::Long-term survival rates in childhood acute lymphoblastic leukemia (ALL) are currently above 85% due to huge improvements in treatment. However, 15-20% of children still experience relapses. Relapses can either occur in the bone marrow or at extramedullary sites, such as gonads or the central nervous system (CNS), for...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2019.04.003
更新日期:2019-07-01 00:00:00
abstract::When an RhD negative mother is exposed to the RhD positive red cells (usually as transplacental haemorrhage), she develops allo-anti-D which crosses the placenta and then results in the destruction of fetal red cells. Clinical manifestations of RhD haemolytic disease (HDN) range from asymptomatic mild anaemia to hydro...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1054/blre.1999.0123
更新日期:2000-03-01 00:00:00
abstract::A working diagnosis of essential thrombocythemia (ET) is made in the presence of nonreactive thrombocytosis and after the exclusion of another chronic myeloid disorder that may mimic ET in its presentation. Clinically, ET is characterized by vasomotor symptoms, thrombohemorrhagic complications, recurrent fetal loss, a...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1054/blre.2001.0158
更新日期:2001-09-01 00:00:00
abstract::Lymphomas cause significant morbidity and mortality worldwide. A substantial number of patients ultimately relapse after standard treatment. However, the efficacy of these therapies can be counteracted by the patients' immune system, more specifically by myeloid-derived suppressor cells (MDSC). MDSC are a heterogeneou...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2018.04.006
更新日期:2018-11-01 00:00:00
abstract::The anaemia of chronic disease (ACD) is a common haematologic syndrome characterized by hypoferraemia with adequate reticuloendothelial iron stores. Frequently, serum ferritin concentration in these patients is elevated. The pathogenesis of ACD involves abnormalities in red cell survival, the erythropoietic response t...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/S0268-960X(03)00066-3
更新日期:2004-12-01 00:00:00
abstract::Childhood immune thrombocytopenic purpura (ITP) is acute and generally seasonal in nature, suggesting that infectious or environmental agents may trigger the immune response to produce platelet-reactive autoantibodies 4 to 8 weeks following an infection. In general, the patient is well apart from the diffuse bruising ...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1054/blre.2001.0177
更新日期:2002-03-01 00:00:00
abstract::MicroRNAs (miRNAs) have become one of the hottest topics in biology over recent years, but remarkably have only been formally recognized for just over 10 years. These endogenously produced short (19-24 nt) non-coding RNAs have introduced an entirely new paradigm in our understanding of gene control and it is now evide...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2013.04.002
更新日期:2013-05-01 00:00:00
abstract::For many years red blood cells have been described as inert bystanders rather than participants in intercellular signalling, immune function, and inflammatory processes. However, studies are now reporting that red blood cells from healthy individuals regulate immune cell activity and maturation, and red blood cells fr...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2019.100644
更新日期:2020-05-01 00:00:00
abstract::Current trends in the treatment of patients with Stages I and II Hodgkin's disease are discussed in this review. Recommendations for staging procedures and the updated staging classification are described. Long-term results with extended field radiation therapy overall and in subgroups of patients are detailed. As fol...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/0268-960x(93)90022-v
更新日期:1993-03-01 00:00:00
abstract::B19 virus is the first human virus to be shown to be a member of the parvovirus genus. This review is concerned with the diseases associated with B19 virus, their nature, pathogenesis and diagnosis. The virus was discovered by chance in blood donors but has been shown to be a common infection of childhood. Infection m...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/0268-960x(87)90020-8
更新日期:1987-03-01 00:00:00
abstract::Major bacterial infections are most commonly associated with agranulocytosis or an abnormality of immunoglobulins or complement. Occasionally, repeated infections cannot be attributed to these relatively common causes. In such cases, a quantitative abnormality in neutrophil function should be sought. Complete evaluati...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/0268-960x(95)90024-1
更新日期:1995-09-01 00:00:00
abstract::Current genomic technologies have immensely improved disease classification and prognostication of major subtypes of B-cell lymphomas. This novel genetic information has not only aided in diagnosis, but has also revealed a landscape of critical molecular events that determine the biological and clinical behavior of a ...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2015.08.002
更新日期:2016-03-01 00:00:00
abstract::Anemia is present in over two-thirds of patients with malignant hematological disorders. The etiology of anemia predominates from ineffective erythropoiesis from marrow infiltration, cytokine related suppression, erythropoietin suppression, and vitamin deficiency; ineffective erythropoiesis is further exacerbated by a...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2015.02.001
更新日期:2015-09-01 00:00:00
abstract::Idiopathic myelofibrosis is reviewed from several aspects. The historical development of knowledge about this disorder is discussed, from early descriptions of extramedullary hematopoiesis associated with numerous etiologies, a debate over pathogenetic mechanisms, followed by newer evidence which placed this disorder ...
journal_title:Blood reviews
pub_type: 历史文章,杂志文章,评审
doi:10.1016/0268-960x(91)90041-a
更新日期:1991-06-01 00:00:00
abstract::Hemophilia A is an X-linked hereditary bleeding disorder due to the deficiency of coagulation factor VIII (FVIII). According to the degree of FVIII deficiency, mild, moderate or severe forms are recognized. Although patients with mild hemophilia A usually bleed excessively only after trauma or surgery, those with seve...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2013.06.002
更新日期:2013-07-01 00:00:00
abstract::The term epigenetics defines a heritable alteration in gene expression without an accompanying change in primary DNA sequence. Two major mechanisms that foster epigenetic changes are DNA methylation at cytosine bases within a CpG dinucleotide and post-translational histone modifications. Disruption of the balanced epi...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2005.01.006
更新日期:2006-01-01 00:00:00
abstract::The unstable haemoglobin haemolytic anaemias result from the presence in the red cell of a structurally abnormal haemoglobin variant. There are many mutations producing unstable haemoglobins; most are single amino acid replacements that affect a few key areas of the haemoglobin structure. A wide range of haemoglobin i...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/0268-960x(93)90002-l
更新日期:1993-09-01 00:00:00
abstract::Splenomegaly is a feature of a broad range of diseases, and presents to clinicians in many fields. This review examines the aetiology of splenomegaly in the developed world, and describes a logical approach to the patient with splenomegaly. In some patients, extensive radiological and laboratory investigations will fa...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/j.blre.2008.10.001
更新日期:2009-05-01 00:00:00
abstract::Cytogenetic analyses in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) have revealed a great number of non-random chromosome abnormalities. In many instances, molecular studies of these abnormalities identified specific genes implicated in the process of leukemogenesis. The more common chromosome ...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/S0268-960X(03)00040-7
更新日期:2004-06-01 00:00:00
abstract::Advances in molecular genetic understanding of disease processes has been extended to a number of phagocytic disorders. Most of these disorders were extensively characterized at the functional and protein level prior to cloning of the relevant genes. Nucleotide sequence data has been essential for establishing the mec...
journal_title:Blood reviews
pub_type: 杂志文章,评审
doi:10.1016/0268-960x(89)90004-0
更新日期:1989-06-01 00:00:00