1,547 results match your criteria Clinical Hematology[Journal]


Clinical variability and molecular characterization of Hbs/Gγ (Aγδβ)0-thal and Hbs/HPFH in Indian sickle cell disease patients: AIIMS experience.

Hematology 2019 Dec;24(1):349-352

a Department of Hematology , All India Institute of Medical Sciences , New Delhi , India.

Introduction: In sickle cell disease (SCD) patients, among the predictors of survival, HbF levels play a significant role in lowering the morbidity and mortality. Coinheritance of δβ thalassemia and hereditary persistence of fetal hemoglobin (HPFH) may contribute to variable HbF levels in SCD patients, thus influencing their clinicopathological profile. Such cases are sparsely documented in the literature and thus, we screened the presence of δβ thalassemia and HPFH in 126 cases of SCD with high HbF. Read More

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http://dx.doi.org/10.1080/16078454.2019.1579985DOI Listing
December 2019

Long non-coding RNAs MALAT1, MIAT and ANRIL gene expression profiles in beta-thalassemia patients: a cross-sectional analysis.

Hematology 2019 Dec;24(1):308-317

e Department of Biochemistry, Faculty of Medicine , Northern Border University , Arar , Saudi Arabia.

Objectives: Beta-thalassemia (β-thal) is one of the most common genetic disorders worldwide. Multiple genetic and epigenetic mechanisms could be implicated in the pathogenesis and/or phenotype variations. We sought to explore the serum expression profile of three disease-related long non-coding RNAs (lncRNAs) in a sample of Egyptian β-thal patients with correlation to the patients' clinicolaboratory data. Read More

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http://dx.doi.org/10.1080/16078454.2019.1570616DOI Listing
December 2019
3 Reads
1.189 Impact Factor

Denosumab effects on serum levels of the bone morphogenetic proteins antagonist noggin in patients with transfusion-dependent thalassemia and osteoporosis.

Hematology 2019 Dec;24(1):318-324

b Department of Clinical Therapeutics , School of Medicine, National and Kapodistrian University of Athens , Athens , Greece.

Introduction: Noggin is an antagonist of bone morphogenetic proteins (BMPs) and has a strong effect on osteogenesis. Osteoporosis is a common complication of transfusion dependent beta-thalassemia (TDT) and denosumab has been recently emerged as a promising therapeutic option. This was a post hoc investigation of serum noggin levels among TDT patients with osteoporosis who participated in a randomized, placebo-control, phase 2b study. Read More

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http://dx.doi.org/10.1080/16078454.2019.1570617DOI Listing
December 2019
3 Reads

TACO and TRALI: biology, risk factors, and prevention strategies.

Authors:
Nareg Roubinian

Hematology Am Soc Hematol Educ Program 2018 11 14;2018(1):585-594. Epub 2018 Dec 14.

Blood Systems Research Institute, San Francisco, CA; Kaiser Permanente Northern California Medical Center and Division of Research, Oakland, CA; and Department of Laboratory Medicine, University of California, San Francisco, CA.

Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion-related morbidity and mortality. These adverse events are characterized by acute pulmonary edema within 6 hours of a blood transfusion and have historically been difficult to study due to underrecognition and nonspecific diagnostic criteria. However, in the past decade, in vivo models and clinical studies utilizing active surveillance have advanced our understanding of their epidemiology and pathogenesis. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324877PMC
November 2018
1 Read

International sentinel site surveillance of patients with transfusional hemosiderosis treated with deferasirox in actual practice setting.

Hematology 2019 Dec;24(1):238-246

h Ain Shams University , Cairo , Egypt.

Objective: The study evaluates the long-term deferasirox treatment of adult and pediatric patients with chronic transfusional iron overload in clinical practice.

Methods: In this non-interventional study, patients were observed for up to 3 years from initiation of deferasirox treatment both prospectively and retrospectively for up to 1 year prior to enrollment. The primary end points were the proportion of patients with ≥1 notable increase in serum creatinine (SCr), and ≥1 notable increase in alanine aminotransferase (ALT). Read More

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http://dx.doi.org/10.1080/16078454.2018.1558758DOI Listing
December 2019
3 Reads
1.189 Impact Factor

Long-term safety and efficacy of deferasirox in patients with myelodysplastic syndrome, aplastic anemia and other rare anemia in Taiwan.

Hematology 2019 Dec;24(1):247-254

k Department of Internal Medicine , Chung Shan Medical University Hospital , Taichung , Taiwan.

Objective: Patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemia require chronic blood transfusions which can lead to iron overload and subsequent excess iron-mediated complications. Intensive iron chelation with deferasirox could remove excess iron and can alleviate these events; however, the long-term safety and efficacy in Chinese population are not clearly characterized. This study examined the long-term efficacy and safety of deferasirox in a real-world setting in Taiwan. Read More

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http://dx.doi.org/10.1080/16078454.2018.1557860DOI Listing
December 2019
7 Reads

Drug-associated thrombocytopenia.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):576-583

Transfusion Medicine, Medical Faculty of Tubingen, University of Tubingen, Tubingen, Germany.

Many drugs have been implicated in drug-induced immune thrombocytopenia (DITP). Patients with DITP develop a drop in platelet count 5 to 10 days after drug administration with an increased risk of hemorrhage. The diagnosis of DITP is often challenging, because most hospitalized patients are taking multiple medications and have comorbidities that can also cause thrombocytopenia. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246020PMC
November 2018
5 Reads

How do we diagnose immune thrombocytopenia in 2018?

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):561-567

Michael G. DeGroote School of Medicine, Department of Medicine and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

In this report, we will review the various clinical and laboratory approaches to diagnosing immune thrombocytopenia (ITP), with a focus on its laboratory diagnosis. We will also summarize the results from a number of laboratories that have applied techniques to detect anti-platelet autoantibodies as diagnostic tests for ITP. Although there is considerable variability in methods among laboratories, there is general agreement that platelet autoantibody testing has a high specificity but low sensitivity. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245958PMC
November 2018
9 Reads

Shifting ground and gaps in transfusion support of patients with hematological malignancies.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):553-560

Laboratory Medicine and Pathobiology (Transfusion Medicine) and Medicine (Clinical Hematology), University Health Network/University of Toronto, Toronto, ON, Canada.

The transfusion support of hematological malignancies considers 2 dimensions: the quantity of what we order (in terms of triggers, doses, targets, and intervals), and the special qualities thereof (with respect to depths of matching and appropriate product modifications). Meanwhile, transfusion-related enhancements in the quantity and quality of life may not be dose dependent but rather tempered by unintended patient harms and system strains from overexposure. Evidence and guidelines concur in endorsing clinically noninferior conservative red blood cell (RBC) transfusion care strategies (eg, triggering at hemoglobin <7-8 g/dL and in single-unit doses for stable, nonbleeding inpatients). Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246005PMC
November 2018
4 Reads

Beyond plasma exchange: novel therapies for thrombotic thrombocytopenic purpura.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):539-547

Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

The advent of plasma exchange has dramatically changed the prognosis of acute thrombotic thrombocytopenic purpura (TTP). Recent insights into TTP pathogenesis have led to the development of novel therapies targeting pathogenic anti-ADAMTS13 antibody production, von Willebrand factor (VWF)-platelet interactions, and ADAMTS13 replacement. Retrospective and prospective studies have established the efficacy of rituximab as an adjunct to plasma exchange for patients with acute TTP, either upfront or for refractory disease. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246029PMC
November 2018
11 Reads

Clinical and laboratory diagnosis of TTP: an integrated approach.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):530-538

Department of Medicine and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Thrombotic thrombocytopenia purpura (TTP) is a rare, life-threatening disease with an incidence of approximately 2 persons per million per year. It is characterized by severe deficiency of the von Willebrand cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), leading to formation of platelet-rich thrombi in the microvasculature. Prompt initiation of appropriate therapy, particularly plasma exchange, may be life-saving. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246034PMC
November 2018
11 Reads

Measuring success: utility of biomarkers in sickle cell disease clinical trials and care.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):482-492

Division of Hematology/Oncology and UPMC Heart, Lung and Blood Vascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Progress in the care of sickle cell disease (SCD) has been hampered by the extreme complexity of the SCD phenotype despite its monogenic inheritance. While epidemiological studies have identified clinical biomarkers of disease severity, with a few exceptions, these have not been routinely incorporated in clinical care algorithms. Furthermore, existing biomarkers have been poorly apt at providing objective parameters to diagnose sickle cell crisis, the hallmark, acute complication of SCD. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246014PMC
November 2018
10 Reads

The current state of sickle cell trait: implications for reproductive and genetic counseling.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):474-481

Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD.

Sickle cell trait (SCT) is unique among the carrier states that are identified during newborn screening. Unlike other heterozygous states for rare recessive diseases, SCT is exceedingly prevalent throughout regions of the world, making sickle cell disease one of the most common monogenetic diseases worldwide. Because of this high frequency, reproductive counseling is of paramount importance. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245976PMC
November 2018
2 Reads

A brief, but comprehensive, guide to clonal evolution in aplastic anemia.

Authors:
Daria V Babushok

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):457-466

Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA; and.

Acquired aplastic anemia (AA) is an immune-mediated bone marrow aplasia that is strongly associated with clonal hematopoiesis upon marrow recovery. More than 70% of AA patients develop somatic mutations in their hematopoietic cells. In contrast to other conditions linked to clonal hematopoiesis, such as myelodysplastic syndrome (MDS) or clonal hematopoiesis of indeterminate potential in the elderly, the top alterations in AA are closely related to its immune pathogenesis. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245980PMC
November 2018
12 Reads

Activity of eltrombopag in severe aplastic anemia.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):450-456

Division of Hematology, Hospital A Beneficência Portuguesa, Sao Paulo, Brazil.

Since the approval of horse antithymocyte globulin (ATG) decades ago, there was a long hiatus in therapies with activity in severe aplastic anemia (SAA). This scenario changed in 2014 when eltrombopag, a thrombopoietin receptor agonist, was approved for SAA after an insufficient response to initial immunosuppressive therapy (IST). The basis for this approval was the observation of single-agent activity of eltrombopag in this patient population, where 40% to 50% recovered blood counts at times involving >1 lineage. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245975PMC
November 2018
2 Reads

Anticoagulating patients with high-risk acquired thrombophilias.

Authors:
Leslie Skeith

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):439-449

Division of Hematology and Hematological Malignancies, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Canada; and Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.

Antiphospholipid syndrome (APS), heparin-induced thrombocytopenia, and paroxysmal nocturnal hemoglobinuria are 3 acquired thrombophilias that carry a high risk of venous and arterial thromboembolism. Management of these conditions has largely included anticoagulation with a vitamin K antagonist after an initial period of a parenteral anticoagulant, for as long as the thrombotic risk is still present. The available evidence for the use of direct oral anticoagulants (DOACs) is limited and primarily consists of case series and cohort studies, which are summarized in this chapter. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246016PMC
November 2018
2 Reads

Breadth of complications of long-term oral anticoagulant care.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):432-438

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

The majority of patients with venous thromboembolism (VTE) have a considerable long-term risk of recurrence and may require extended duration of anticoagulant treatment after the initial 3 to 6 months. The decision to extend treatment is based not only on the individual risk of recurrence, but should also consider the potential complications associated with anticoagulation, taking into account that anticoagulant drugs are among the drugs most frequently associated with hospital admission due to adverse drug reactions. The most feared complication of oral anticoagulants is bleeding, which in some cases may be fatal or may affect critical organs. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245998PMC
November 2018
2 Reads

Who should get long-term anticoagulant therapy for venous thromboembolism and with what?

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):426-431

Ottawa Blood Disease Centre, Ottawa Hospital, Ottawa, Ontario, Canada.

After an initial 3 to 6 months of anticoagulation for venous thromboembolism (VTE), clinicians and patients face an important question: "Do we stop anticoagulants or continue them indefinitely?" The decision is easy in some scenarios (eg, stop in VTE provoked by major surgery). In most scenarios, which are faced on a day-to-day basis in routine practice, it is a challenging decision because of uncertainty in estimates in the long-term risks (principally major bleeding) and benefits (reducing recurrent VTE) and the tight trade-offs between them. Once the decision is made to continue, the next question to tackle is "Which anticoagulant?" Here again, it is a difficult decision because of the uncertainty with regard to estimates of efficacy and the safety of anticoagulant options and the tight trade-offs between choices. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246028PMC
November 2018
1 Read

Management of thrombosis in children and neonates: practical use of anticoagulants in children.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):399-404

Department of Clinical Haematology, Royal Children's Hospital, Haematology Research Murdoch Children's Research Institute, School of Nursing, University of Melbourne, Melbourne, VIC, Australia.

Venous thrombosis (VTE) in children and neonates presents numerous management challenges. Although increasing in frequency, VTE in children and neonates is still uncommon compared with adults. The epidemiology of VTE is vastly different in neonates vs children vs adolescents vs adults. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245972PMC
November 2018
3 Reads

Evaluation and management of heavy menstrual bleeding in adolescents: the role of the hematologist.

Authors:
Sarah H O'Brien

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):390-398

Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH; and.

Heavy menstrual bleeding (HMB) is frequently reported by adolescents. The role of the hematologist is threefold in evaluating such patients: (1) perform a clinical and laboratory evaluation for an underlying bleeding disorder on the basis of the degree of clinical suspicion, (2) identify and manage any concomitant iron deficiency, and (3) provide input to the referring provider regarding the management of HMB, particularly for patients with identified hemostatic defects. Several clues in the menstrual history should raise suspicion for an underlying bleeding disorder, such as menses lasting >7 days, menstrual flow which soaks >5 sanitary products per day or requires product change during the night, passage of large blood clots, or failure to respond to conventional therapies. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246024PMC
November 2018
4 Reads

Autoimmune hemolytic anemia.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):382-389

Department of Haematology, Leeds Teaching Hospitals, Leeds, United Kingdom.

The diagnosis of autoimmune hemolytic anemia (AIHA) can be made with a stepwise approach that aims to identify laboratory and clinical evidence of hemolysis and then determine the immune nature of hemolysis with the direct anti-globulin test. Once alternative causes for these findings have been excluded, AIHA is established, and the clinician must search for secondary causes, as well as identify the type of AIHA. Rituximab is now the preferred second-line treatment for primary warm AIHA and first-line treatment for primary cold agglutinin disease (CAD), either as monotherapy or combined with bendamustine. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246027PMC
November 2018
11 Reads

Inherited hemolytic anemia: a possessive beginner's guide.

Authors:
Narla Mohandas

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):377-381

New York Blood Center, New York, NY.

Significant advances have been made in diagnosis and clinical management of inherited red cell membrane disorders that result in hemolytic anemia. Membrane structural defects lead to hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), whereas altered membrane transport function accounts for hereditary xerocytosis (HX) and hereditary overhydrated stomatocytosis (OHS). The degrees of membrane loss and resultant increases in cell sphericity determine the severity of anemia in HS and HE, and splenectomy leads to amelioration of anemia by increasing the circulatory red cell life span. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245988PMC
November 2018
2 Reads

Complement-driven anemia: more than just paroxysmal nocturnal hemoglobinuria.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):371-376

Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Atypical hemolytic uremic syndrome (aHUS); hemolysis, elevated liver function tests, and low platelets syndrome; and transplant-associated thrombotic microangiopathy are related conditions, in that many patients harbor germline heterozygous mutations in genes that regulate the alternative pathway of complement (APC). Penetrance is variable because development of clinically significant disease appears to require supervention of a process such as inflammation. Complement activation on the endothelial surfaces leads to endothelial damage, platelet consumption, microthrombi, and a mechanical hemolytic anemia with schistocytes. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245985PMC
November 2018
2 Reads

Beyond transfusion therapy: new therapies in thalassemia including drugs, alternate donor transplant, and gene therapy.

Authors:
John Porter

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):361-370

University College London, London, United Kingdom.

Transfusion combined with chelation therapy for severe β thalassemia syndromes (transfusion-dependent thalassemia [TDT]) has been successful in extending life expectancy, decreasing comorbidities and improving quality of life. However, this puts lifelong demands not only on the patients but also on the health care systems that are tasked with delivering long-term treatment and comprehensive support. Prevention programs and curative approaches are therefore an important part of overall strategy. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245990PMC
November 2018
2 Reads

Role of the anticoagulant monitoring service in 2018: beyond warfarin.

Authors:
Nathan P Clark

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):348-352

Kaiser Permanente Colorado, Aurora, CO; and Department of Clinical Pharmacy, Colorado University Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO.

The direct oral anticoagulants (DOACs) have a wide therapeutic index, few drug interaction, no dietary interactions and do not require dose adjustment according to the results of routine coagulation testing. Despite these advantages over warfarin, the DOACs remain high risk medications. There is evidence that non-adherence, off-label dosing and inadequate care transitions during DOAC therapy increase the risk of bleeding and thromboembolic complications. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246023PMC
November 2018
2 Reads

Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):318-325

Division of Translational Medicine & Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Castleman disease (CD) describes a heterogeneous group of hematologic disorders that share characteristic lymph node histopathology. Patients of all ages present with either a solitary enlarged lymph node (unicentric CD) or multicentric lymphadenopathy (MCD) with systemic inflammation, cytopenias, and life-threatening multiple organ dysfunction resulting from a cytokine storm often driven by interleukin 6 (IL-6). Uncontrolled human herpesvirus-8 (HHV-8) infection causes approximately 50% of MCD cases, whereas the etiology is unknown in the remaining HHV-8-negative/idiopathic MCD cases (iMCD). Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245974PMC
November 2018
2 Reads

JMML genomics and decisions.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):307-312

Department of Pediatrics and Adolescent Medicine, University Children's Hospital, University of Freiburg, Freiburg, Germany.

Juvenile myelomonocytic leukemia (JMML) is a unique clonal hematopoietic disorder of early childhood characterized by hyperactivation of the RAS signal transduction pathway. Approximately 90% of patients harbor molecular alteration in 1 of 5 genes (), which define genetically and clinically distinct JMML subtypes. Three subtypes, , and -mutated JMML, are characterized by heterozygous somatic gain-of-function mutations in non syndromic children, while two subtypes, JMML in neurofibromatosis type 1 and in JMML in children with CBL syndrome, are characterized by germ line RAS disease and acquired biallelic inactivation of the respective tumor suppressor genes in hematopoietic cells. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245977PMC
November 2018
4 Reads

Ethical conundrums in pediatric genomics.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):301-306

Department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Cleveland Clinic Children's Hospital, Cleveland, OH.

Recent genomic discoveries have improved our understanding of many hematologic diseases and led to novel therapeutic options for many patients. The rapid decrease in the cost of genomic testing has enabled widespread use of clinical genomic testing. However, these advances are accompanied by concomitant challenging ethical concerns. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245967PMC
November 2018
1 Read

Using genomics to define pediatric blood cancers and inform practice.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):286-300

Department of Pediatrics, Benioff Children's Hospital and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.

Over the past decade, there has been exponential growth in the number of genome sequencing studies performed across a spectrum of human diseases as sequencing technologies and analytic pipelines improve and costs decline. Pediatric hematologic malignancies have been no exception, with a multitude of next generation sequencing studies conducted on large cohorts of patients in recent years. These efforts have defined the mutational landscape of a number of leukemia subtypes and also identified germ-line genetic variants biologically and clinically relevant to pediatric leukemias. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245969PMC
November 2018
2 Reads

The MDS genomics-prognosis symbiosis.

Authors:
Aziz Nazha

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):270-276

Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.

Myelodysplastic syndromes (MDS) are clonal disorders characterized by the accumulation of complex genomic abnormalities that define disease phenotype, prognosis, and the risk of transformation to acute myeloid leukemia. The clinical manifestations and overall outcomes of MDS are very heterogeneous with an overall survival that can be measured in years for some patients to a few months for others. Prognostic scoring systems are important staging tools that aid physicians in their treatment recommendations and decision-making and can help patients understand their disease trajectory and expectations. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246025PMC
November 2018
5 Reads

Clinical consequences of clonal hematopoiesis of indeterminate potential.

Authors:
David P Steensma

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):264-269

Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.

Clonally restricted hematopoiesis is a common aging-associated biological state that predisposes to subsequent development of a hematological malignancy or cardiovascular death. Clonal expansion driven by leukemia-associated somatic mutations, such as , , or , is best characterized, but oligoclonality can also emerge without recognized leukemia-driver mutations, perhaps as a result of stochastic neutral drift. Murine models provide compelling evidence that a major mechanism of increased cardiovascular mortality in the context of clonal hematopoiesis is accelerated atherogenesis driven by inflammasome-mediated endothelial injury, resulting from proinflammatory interactions between endothelium and macrophages derived from circulating clonal monocytes. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245996PMC
November 2018
10 Reads

Relapsed CLL: sequencing, combinations, and novel agents.

Authors:
Jennifer R Brown

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):248-255

CLL Center, Division of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.

Although the therapy of chronic lymphocytic leukemia (CLL) has changed rapidly over the last 5 years, the key considerations in selecting a therapy for a previously treated patient with CLL continue to include the nature of the prior therapy and the duration of prior remission to that therapy, the prognostic features of the disease, and the health and comorbidities of the patient in question. For patients treated initially with chemoimmunotherapy, randomized trials have demonstrated the benefit of targeted therapy. Retrospective data suggest that ibrutinib is preferred as a first kinase inhibitor, whereas recent data with venetoclax and rituximab may challenge the choice of ibrutinib as a first novel agent in the relapsed setting. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245984PMC
November 2018
9 Reads

Selecting Frontline Therapy for CLL in 2018.

Authors:
Nitin Jain

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):242-247

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.

The treatment landscape of chronic lymphocytic leukemia (CLL) has changed dramatically in the last few years. The role of chemoimmunotherapy has declined significantly for patients with CLL. Fludarabine, cyclophosphamide, rituximab chemotherapy remains the standard frontline therapy for young fit patients with CLL, especially if mutated. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245995PMC
November 2018
7 Reads

Biology-driven developments in the therapy of acute graft-versus-host disease.

Authors:
Robert Zeiser

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):236-241

Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, Freiburg University Medical Center, Freiburg, Germany.

Allogeneic hematopoietic cell transplantation is a potentially curative treatment of different hematological malignancies. A major life-threatening complication is acute graft-versus-host disease (GVHD), in particular when the disease becomes steroid refractory. Based on the detection of pathogenic cytokines, chemokines, and T-cell subsets in individuals developing GVHD or experimental GVHD models, different therapeutic strategies have been developed. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245989PMC
November 2018
1 Read

Current approaches to prevent and treat GVHD after allogeneic stem cell transplantation.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):228-235

Blood and Marrow Transplant Program, Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.

Allogeneic hematopoietic cell transplantation is a potentially curative therapy for many malignant and nonmalignant hematologic diseases. Graft-versus-host disease (GVHD) is a common complication after transplantation and remains a major cause of morbidity and mortality, limiting the success of a potentially curative transplant. This paper reviews the current and emerging strategies in GVHD prevention and treatment. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246030PMC
November 2018
12 Reads

GVHD: biology matters.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):221-227

The Tisch Cancer Institute and Division of Hematology/Medical Oncology, The Icahn School of Medicine at Mount Sinai Hospital, New York, NY.

Acute graft-versus-host disease (GVHD) targets the crypts in the gastrointestinal (GI) tract that are responsible for the self-renewal of the intestinal mucosa. Recent advances in the identification and culture of intestinal stem cells have improved our understanding of the interactions between the microbiome and the immune system (both innate and adaptive) that are key to the pathophysiology of GVHD. The identification of serum biomarkers that best predict long-term GVHD outcomes derive from the GI tract and have focused attention on cellular elements that act as shields against GVHD as well as its targets. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245966PMC
November 2018
2 Reads

Where does PD-1 blockade fit in HL therapy?

Authors:
Alex F Herrera

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):213-220

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA.

Genetic alterations of the / locus on chromosome 9p24.1 are a defining biological feature of classical Hodgkin lymphoma (HL). The resulting programmed death-ligand 1 (PD-L1) expression on Hodgkin Reed-Sternberg cells as well as the PD-L1 expressed in the HL microenvironment result in an ineffective host antitumor immune response and make HL a ripe target for programmed cell death-1 (PD-1) blockade. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246012PMC
November 2018
17 Reads

Where to start? Upfront therapy for follicular lymphoma in 2018.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):185-188

Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.

The initial approach to the management of follicular lymphoma (FL) is challenging for patients and physicians. Most FL patients present with minimal symptoms; given the lack of a survival benefit to early treatment in this population, a period of observation without therapy is often appropriate. Once there is disease progression beyond low-tumor-burden criteria or symptoms prompting intervention, patients may be considered for an array of potential treatment options. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246009PMC
November 2018
21 Reads

We do still transplant CML, don't we?

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):177-184

Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom.

The remarkable clinical activity of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has transformed patient outcome. Consequently, allogeneic stem cell transplantation (allo-SCT) is no longer the only treatment modality with the ability to deliver long-term survival. In contrast to the central position it held in the treatment algorithm 20 years ago, allografting is now largely reserved for patients with either chronic-phase disease resistant to TKI therapy or advanced-phase disease. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246013PMC
November 2018
5 Reads

The argument for using imatinib in CML.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):161-167

Department of Clinical Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom; and.

June 2018 was the 20th anniversary of the clinical use of the first tyrosine kinase inhibitor (TKI), imatinib, for chronic myeloid leukemia. Since then, the change in prognosis for patients with this disease is one of the major success stories of modern cancer medicine. The dilemmas that face physicians and patients are no longer only those concerned with delaying inevitable progression to the terminal blastic phase or selecting the individuals most likely to benefit from allogeneic stem-cell transplantation; rather, they are now focused also on the choice of TKI, the management of comorbidities and adverse effects, strategies to improve quality of life, and the appropriateness of a trial of therapy discontinuation. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246007PMC
November 2018
15 Reads

Adolescent angst: enrollment on clinical trials.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):154-160

Division of Health Policy and Management, University of Minnesota, Minneapolis, MN.

Survival among adolescents and young adults (AYAs) ages 15 to 39 with cancer has not improved to the same extent as that of pediatric and older adult cancer patients, which is thought to relate, in part, to the lower participation of AYAs in clinical trials. Because significant efforts have been made to improve clinical trial enrollment for AYAs, we (1) present contemporary clinical trial enrollment rates by cancer type, sociodemographic characteristics, and treatment setting and (2) discuss provider-, patient-, and system-level barriers to clinical trial participation. Contemporary studies examining clinical trial enrollment among AYAs have continued to find low overall participation relative to pediatric populations, with most studies observing no significant improvements in enrollment over time. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246006PMC
November 2018
1 Read

Long-term complications in adolescent and young adult leukemia survivors.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):146-153

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Adolescents and young adults (AYAs) with cancer, defined by the National Cancer Institute as having been diagnosed between the ages of 15 and 39 years old, have not benefited from the same improvements in quality of outcomes and survival that have been seen for individuals diagnosed in childhood or as older adults. Although is leukemia composed of a diverse group of diagnoses, leukemia AYA survivors share unique vulnerabilities with other AYA diagnostic groups. They will spend the majority of their lives as survivors, with clear evidence of adverse medical conditions, health care requirements, and social and psychological needs that differ not only from their peers but also, from the needs of other cancer survivor populations. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245964PMC
November 2018
2 Reads

Genetics and prognosis of ALL in children vs adults.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):137-145

Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN.

Acute lymphoblastic leukemia (ALL) is characterized by genetic alterations that block differentiation, promote proliferation of lymphoid precursor cells, and are important for risk stratification. Although ALL is less common in adolescents and young adults (AYAs) and adults than children, survival rates are inferior, and long-term prognosis for adults is poor. Thus, ALL remains a challenging disease to treat in the AYA and adult populations. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245970PMC
November 2018
1 Read

The new tool "" in advanced systemic mastocytosis.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):127-136

Divisions of Hematology and.

Mastocytosis is a rare disease characterized by KIT-driven expansion and accumulation of neoplastic mast cells in various tissues. Although mediator symptoms related to mast cell activation can impose a symptom burden in cutaneous disease and across the spectrum of systemic mastocytosis subtypes, the presence of an associated hematologic neoplasm and/or organ damage denotes advanced disease and the potential for increased morbidity and mortality. In addition to the revised 2016 World Health Organization classification of mastocytosis, a new diagnostic and treatment toolkit, tethered to enhanced molecular characterization and monitoring, is poised to transform the management of patients with advanced systemic mastocytosis (advSM). Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245986PMC
November 2018
8 Reads

Managing myelofibrosis (MF) that "blasts" through: advancements in the treatment of relapsed/refractory and blast-phase MF.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):118-126

Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX.

Myelofibrosis (MF) is the most aggressive form of Philadelphia chromosome-negative myeloproliferative neoplasm, and it is complicated by severe symptom burden, thrombotic events, infections, cytopenias, and transformation to acute myeloid leukemia (AML). Ruxolitinib, the first-line therapy for symptomatic or intermediate- and high-prognostic risk MF, has improved overall survival for this population. However, approximately one-half of MF patients will discontinue ruxolitinib by the first few years of therapy due to a spectrum of resistance, intolerance, relapse, or progression to blast phase disease. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245993PMC
November 2018
8 Reads

JAK2 (and other genes) be nimble with MPN diagnosis, prognosis, and therapy.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):110-117

Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and.

Now that the spectrum of somatic mutations that initiate, propagate, and drive the progression of myeloproliferative neoplasms (MPNs) has largely been defined, recent efforts have focused on integrating this information into clinical decision making. In this regard, the greatest progress has been made in myelofibrosis, in which high-molecular-risk mutations have been identified and incorporated into prognostic models to help guide treatment decisions. In this chapter, we focus on advances in 4 main areas: (1) What are the MPN phenotypic driver mutations? (2) What constitutes high molecular risk in MPN (focusing on )? (3) How do we risk-stratify patients with MPN? And (4) What is the significance of molecular genetics for MPN treatment? Although substantial progress has been made, we still have an incomplete understanding of the molecular basis for phenotypic diversity in MPN, and few rationally designed therapeutic approaches to target high-risk mutations are available. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246021PMC
November 2018
2 Reads

Approach to the treatment of the older, unfit patient with myeloma from diagnosis to relapse: perspectives of a US hematologist and a geriatric hematologist.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):88-96

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

Mrs. A. is a 73-year-old woman who has developed increasing fatigue and lower back pain over the past year. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245982PMC
November 2018
2 Reads

Treatment approach for the older, unfit patient with myeloma from diagnosis to relapse: perspectives of a European hematologist.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):83-87

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

Mrs. A. is a 73-year-old woman who has developed increasing fatigue and lower back pain over the past year. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245965PMC
November 2018
14 Reads

Novel therapies for relapsed/refractory aggressive lymphomas.

Authors:
Jonathon B Cohen

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):75-82

Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.

Most patients with aggressive non-Hodgkin lymphoma will be cured with initial chemoimmunotherapy; however, most patients with relapsed disease will not be cured and will die as a result of their disease. In these cases, continued treatment with conventional chemotherapy is typically not of benefit and can contribute to significant toxicities and decreased quality of life for patients. Fortunately, a number of therapies are currently available or under investigation for this group of patients, ranging from oral tyrosine kinase inhibitors targeting multiple pathways within the malignant cells to adoptive cellular therapies that harness the patient's immune system to fight disease. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245978PMC
November 2018
22 Reads

Genomics of aggressive B-cell lymphoma.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):69-74

Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, AZ.

The growing body of genomic information collected and applied to mature aggressive B-cell lymphoma diagnosis and management has exploded over the last few years due to improved technologies with high-throughput capacity, suitable for use on routine formalin-fixed, paraffin-embedded tissue biopsies, and decreasing costs. These techniques have made evaluation of complete DNA sequences, RNA-expression patterns, translocations, copy-number alterations, loss of heterozygosity, and DNA-methylation patterns possible on a genome-wide level. This chapter will present a case of aggressive B-cell lymphoma and discuss the most important genomic abnormalities that characterize this group of entities in the recent update to the fourth edition of the World Health Organization (WHO) lymphoma classification system. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.69DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245962PMC
November 2018
1 Read