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Hematology—the Education Program of the American Society of Hematology

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https://www.readbyqxmd.com/read/29222326/acquired-ribosomopathies-in-leukemia-and-solid-tumors
#1
REVIEW
Adrianna Vlachos
A mutation in the gene encoding the small subunit-associated ribosomal protein RPS19, leading to RPS19 haploinsufficiency, is one of the ribosomal protein gene defects responsible for the rare inherited bone marrow failure syndrome Diamond Blackfan anemia (DBA). Additional inherited and acquired defects in ribosomal proteins (RPs) continue to be identified and are the basis for a new class of diseases called the ribosomopathies. Acquired RPS14 haploinsufficiency has been found to be causative of the bone marrow failure found in 5q- myelodysplastic syndromes...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222325/cells-to-prevent-treat-relapse-following-allogeneic-stem-cell-transplantation
#2
REVIEW
Andrew C Dietz, Alan S Wayne
Relapse of cancer remains one of the primary causes of treatment failure and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). A multitude of approaches have been used in the management of posttransplant relapse. This review focuses on recent data with cellular therapies designed to treat or prevent posttransplant relapse of hematologic malignancies, although many of these therapeutic approaches also have applications to solid tumors and in the nontransplant setting. Currently available cell therapies include second transplant, natural killer cells, monocyte-derived dendritic cell vaccines, and lymphocytes via donor lymphocyte infusion, antigen-primed cytotoxic T lymphocytes, cytokine-induced killer cells, marrow-infiltrating lymphocytes, and chimeric antigen receptor T cells...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222324/pharmacologic-agents-to-prevent-and-treat-relapse-after-allogeneic-hematopoietic-cell-transplantation
#3
REVIEW
Robert J Soiffer, Yi-Bin Chen
No abstract text is available yet for this article.
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222323/graft-versus-tumor-effects-and-why-people-relapse
#4
REVIEW
J H Frederik Falkenburg, Inge Jedema
Graft-versus-tumor (GVT) reactivity mediated by donor T cells in the context of allogeneic stem cell transplantation (alloSCT) is one of the most potent forms of cellular immunotherapy. The antitumor effect against hematologic malignancies is mediated by a polyclonal T-cell response targeting polymorphic antigens expressed on hematopoietic tissues of the recipient, leaving donor hematopoiesis in the patient after transplantation unharmed. Fortunately, hematopoietic tissues (including malignant hematopoietic cell populations) are relatively susceptible to T-cell recognition...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222322/inferior-vena-cava-filter-use-and-patient-safety-legacy-or-science
#5
REVIEW
William Geerts, Rita Selby
There has been a dramatic increase in vena cava filter (VCF) use over the past 20 years in the absence of evidence that filters provide a net patient benefit or are required in most cases. This increase is largely attributable to the availability of retrievable filters and expanded indications, particularly as primary prophylaxis in patients thought to be at high risk of pulmonary embolism. Substantial variability in VCF use, unrelated to patient clinical factors, has been shown between hospitals, from region to region, and among various countries...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222321/thrombectomy-and-thrombolysis-for-the-prevention-and-treatment-of-postthrombotic-syndrome
#6
REVIEW
Suresh Vedantham
Postthrombotic syndrome (PTS) is a frequent complication of lower-extremity deep vein thrombosis (DVT), occurring in approximately 40% of patients despite the use of anticoagulant therapy. PTS causes significant impairment of patients' health-related quality of life, and no evidence-based therapies have been consistently effective. Catheter-directed thrombolysis and thrombectomy have been shown to remove acute thrombus, and it has been hypothesized they could prevent or reduce PTS. However, because these procedures can be associated with complications, mainly bleeding, randomized trial data are needed to determine when they should be used...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222320/anticoagulation-with-vads-and-ecmo-walking-the-tightrope
#7
REVIEW
Leslie Raffini
The evolution of devices for mechanical circulatory support (MCS), including ventricular assist devices (VADs) for patients with heart failure and extracorporeal membrane oxygenation (ECMO) for patients with acute cardiac or respiratory failure, has improved survival for subsets of critically ill children and adults. The devices are intricate and complex, allowing blood to bypass the heart or lungs (or both). As blood flows through these artificial devices, normal hemostasis is disrupted, coagulation is promoted, and in the absence of anticoagulation, a thrombus may form in the device, resulting in device failure or embolic stroke...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222319/hits-and-misses-in-100-years-of-heparin
#8
REVIEW
Lawrence Rice
Heparin was discovered 100 years ago, and the heparin-induced thrombocytopenia syndrome was described 40 years ago. That the most powerful anticoagulant of the last century can also produce the most extreme prothrombotic diathesis is but one of the paradoxes that surround heparin-induced thrombocytopenia. Standard treatment is alternative anticoagulation. Advances continue to be made regarding pathophysiology, prevention, and treatment. Currently, an epidemic of overdiagnosis threatens the well-being of patients, so efforts to educate clinicians on when and how to make this diagnosis are pressing...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222318/assessing-thrombocytopenia-in-the-intensive-care-unit-the-past-present-and-future
#9
REVIEW
Ryan Zarychanski, Donald S Houston
Thrombocytopenia is common among patients admitted to the intensive care unit (ICU). Multiple pathophysiological mechanisms may contribute, including thrombin-mediated platelet activation, dilution, hemophagocytosis, extracellular histones, ADAMTS13 deficiency, and complement activation. From the clinical perspective, the development of thrombocytopenia in the ICU usually indicates serious organ system derangement and physiologic decompensation rather than a primary hematologic disorder. Thrombocytopenia is associated with bleeding, transfusion, and adverse clinical outcomes including death, though few deaths are directly attributable to bleeding...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222317/thrombocytopenia-in-hospitalized-patients-approach-to-the-patient-with-thrombotic-microangiopathy
#10
REVIEW
Marie Scully
Thrombotic microangiopathies (TMAs), specifically, thrombotic thrombocytopenic purpura (TTP) and complement-mediated hemolytic uremic syndrome (CM-HUS) are acute life-threatening disorders that require prompt consideration, diagnosis, and treatment to improve the high inherent mortality and morbidity. Presentation is with microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) and variable organ symptoms resulting from microvascular thrombi. Neurological and cardiac involvement is most common in TTP and associated with poorer prognosis and primarily renal involvement in CM-HUS...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222316/hla-donor-specific-antibodies-in-allogeneic-hematopoietic-stem-cell-transplantation-challenges-and-opportunities
#11
REVIEW
Douglas E Gladstone, Maria P Bettinotti
Allogenic hematopoietic stem cell recipients may have preformed antibodies directed against foreign HLA antigens. The use of partially HLA-mismatched allogeneic hematopoietic stem cell donors allows for the possibility of the presence of circulating HLA donor-specific antibodies (DSAs) in the recipient. The presence of DSAs at the time of stem cell infusion increases the risk of primary graft failure. More recently developed technology using solid phase immunoassays (SPIs) with fluorochrome-conjugated beads has greatly improved the ability to detect and classify DSAs...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222315/extracorporeal-photopheresis-cellular-therapy-for-the-treatment-of-acute-and-chronic-graft-versus-host-disease
#12
REVIEW
Jennifer Schneiderman
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for many disease states. Despite significant improvements in strategies used to prevent and treat acute and chronic graft-versus-host disease (a/cGVHD), they continue to negatively affect outcomes of HSCT significantly. Standard, first-line treatment consists of corticosteroids; beyond this, there is little consistency in therapeutic regimens. Current options include the addition of various immunosuppressive agents, the use of which puts patients at even higher risks for infection and other morbidities...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222314/plasma-exchange-in-thrombotic-microangiopathies-tmas-other-than-thrombotic-thrombocytopenic-purpura-ttp
#13
REVIEW
Jeffrey L Winters
Thrombotic microangiopathies (TMAs) are a diverse group of disorders that are characterized by common clinical and laboratory features. The most commonly thought-of TMA is thrombotic thrombocytopenic purpura (TTP). Because of the marked improvement in patient mortality associated with the use of therapeutic plasma exchange (TPE) in TTP, this therapy has been applied to all of the TMAs. The issue, however, is that the pathophysiology varies and in many instances may represent a disorder of the endothelium and not the blood; in some cases, the pathophysiology is unknown...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222313/developing-t-cell-therapies-for-lymphoma-without-receptor-engineering
#14
REVIEW
Melanie Grant, Catherine M Bollard
T-cell therapy has emerged from the bench for the treatment of patients with lymphoma. Responses to T-cell therapeutics are regulated by multiple factors, including the patient's immune system status and disease stage. Outside of engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell therapy can be mediated by ex vivo expansion of antigen-specific T cells targeting viral and/or nonviral tumor-associated antigens. These approaches are contributing to enhanced clinical responses and overall survival...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222312/harnessing-the-power-of-the-immune-system-in-non-hodgkin-lymphoma-immunomodulators-checkpoint-inhibitors-and-beyond
#15
REVIEW
Stephen M Ansell
Non-Hodgkin lymphoma is a malignancy of B lymphocytes that typically infiltrate sites of disease, including the lymph nodes, spleen, and bone marrow. Beyond the presence of malignant cells, many immune cells are also present within the tumor microenvironment. Although these immune cells have the potential to regulate the growth of malignant B cells, intratumoral immune cells are unable to eradicate lymphoma cells and most patients with lymphoma have clinical evidence of disease progression. Recent data have identified some of the mechanisms that account for the suppressed antitumor immune response and have created opportunities for treatment to overcome the deficiencies...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222311/role-of-the-microenvironment-across-histological-subtypes-of-nhl
#16
REVIEW
Karin Tarte
Recent progress in next-generation sequencing strategies has revealed the genetic landscape of B-cell non-Hodgkin lymphoma, but the tumor microenvironment is increasingly recognized as crucial to sustaining malignant B-cell survival and growth, subclonal evolution, and drug resistance. The tumor niche is made up of a dynamic and organized network of strongly heterogeneous immune and stromal cell subsets characterized by specific phenotypic, transcriptomic, and functional features. Nonmalignant cell recruitment and plasticity are dictated by lymphoma B cells, which convert their surrounding microenvironment into a supportive niche...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222310/novel-alternate-hemostatic-agents-for-patients-with-inhibitors-beyond-bypass-therapy
#17
REVIEW
Margaret V Ragni
Inhibitor formation is among the most severe complications of hemophilia treatment. With a cumulative incidence of ∼30% in those with severe hemophilia A and ∼3% in those with severe hemophilia B, inhibitors are caused by a T-cell response directed against infused coagulation factor; these inhibitors neutralize factor VIII or IX activity and disrupt normal hemostasis. Inhibitor patients become unresponsive to standard factor treatment and, as an alternative, use bypass treatment (eg, recombinant factor VIIa or factor VIII inhibitor bypass activity)...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222309/using-pharmacokinetics-to-individualize-hemophilia-therapy
#18
REVIEW
Alfonso Iorio
Prevention and treatment of bleeding in hemophilia requires that plasma clotting factor activity of the replaced factor exceeds a defined target level. Most clinical decisions in hemophilia are based on implicit or explicit application of pharmacokinetic measures. The large interindividual variability in pharmacokinetics of factor concentrates suggests that relying on the average pharmacokinetic characteristics of factor concentrates would not allow optimizing the treatment of individual patients; for example, adjusting the frequency of infusions and targeting a specific clotting factor activity level on a case-by-case basis...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222308/hemophilia-gene-therapy-comes-of-age
#19
REVIEW
Lindsey A George
Concurrent with the development of recombinant factor replacement products, the characterization of the F9 and F8 genes over 3 decades ago allowed for the development of recombinant factor products and made the hemophilias a target disease for gene transfer. The progress of hemophilia gene therapy has been announced in 3 American Society of Hematology scientific plenary sessions, including the first "cure" in a large animal model of hemophilia B in 1998, first in human sustained vector-derived factor IX activity in 2011, and our clinical trial results reporting sustained vector-derived factor IX activity well into the mild or normal range in 2016...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222307/secondary-cns-relapse-in-diffuse-large-b-cell-lymphoma-defining-high-risk-patients-and-optimization-of-prophylaxis-strategies
#20
REVIEW
Kerry J Savage
Despite improvement in survival in diffuse large B-cell lymphoma (DLBCL) with the introduction of rituximab, central nervous system (CNS) relapse continues to represent a clinical challenge. A number of studies have evaluated clinical risk factors in an attempt to identify high-risk patients to direct CNS staging investigations and consider prophylaxis strategies. The CNS International Prognostic Index is a robust and reproducible risk model that can identity patients at high risk of CNS relapse, but its specificity remains limited...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
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