Log in to search using one of your social media accounts:

 

Inherited thrombophilia: a double-edged sword.
Authors: Middeldorp S Abstract Inherited thrombophilia is a blood coagulation disorder that increases the risk for venous thromboembolism (VTE). During the last decades, the practice of testing has evolved from testing selected populations, leading to high perceived risks, to broad testing for various conditions that included VTE, arterial thrombosis, and pregnancy complications. Because results of such tests usually do not guide treatment decisions, not testing patients with VTE for inherited thrombophilia is on the "Choosing Wisely" list endorsed by multiple specialty societies, including ASH. Inherited...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Acute promyelocytic leukemia: preventing early complications and late toxicities.
Authors: Abedin S, Altman JK Abstract Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Therapeutic advances have made APL one of the true success stories in oncology, transforming this once lethal disease into the most curable form of AML. For many patients, cure will now be achieved without the use of chemotherapy. It is hoped that limiting chemotherapy will reduce mortality even further, particularly among more vulnerable older adults whose survival lagged behind that of younger patients. It should be noted that early death persis...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Treatment of blastic plasmacytoid dendritic cell neoplasm.
Authors: Sullivan JM, Rizzieri DA Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4(+)CD56(+)CD123(+)lineage(-)MPO(-), although many patients will present with variable expression of CD4, CD56, or alternate plasma...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Therapy-related myeloid neoplasms: does knowing the origin help to guide treatment?
Authors: Heuser M Abstract Therapy-related myeloid neoplasms (t-MN) combine t-MDS and therapy related acute myeloid leukemia (t-AML) patients in one entity because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. In contrast, treatment with alkylating agents has been associated with a longer latency, an initial MDS phase, adverse cytogenetics, and a poor prognos...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Children with rare diseases of neutrophil granulocytes: from therapeutic orphans to pioneers of individualized medicine.
Authors: Klein C Abstract Neutrophil granulocytes are the most abundant immune cells in the blood yet the pathways orchestrating their differentiation and biological function remain incompletely understood. Studying (ultra-) rare patients with monogenetic defects of neutrophil granulocytes may open new horizons to understand basic principles of hematopoiesis and innate immunity. Here, recent insights into genetic factors controlling myelopoiesis and their more general role in biology will be presented in a clinical perspective. Advances in supportive care, first and foremost the use of recombinant human granulocyte...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Autoimmune and other acquired neutropenias.
Discussion of management options emphasizes a conservative approach, with largely supportive care for these mostly benign and self-limited disorders. PMID: 27913460 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Primary immune deficiencies with defects in neutrophil function.
Authors: Dinauer MC Abstract Immune deficiencies resulting from inherited defects in neutrophil function have revealed important features of the innate immune response. Although sharing an increased susceptibility to bacterial and fungal infections, these disorders each have distinctive features in their clinical manifestations and characteristic microbial pathogens. This review provides an update on several genetic disorders with impaired neutrophil function, their pathogenesis, and treatment strategies. These include chronic granulomatous disease, which results from inactivating mutations in the superoxide-genera...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Pure red cell aplasia.
Authors: Means RT Abstract Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorde...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Single-dose intravenous iron for iron deficiency: a new paradigm.
Authors: Auerbach M, Deloughery T Abstract Iron-deficiency anemia is the most common hematologic problem in the world. Although oral iron is often viewed as front-line therapy, extensive published evidence has accumulated that IV iron is superior, in both efficacy and safety, to oral iron in many clinical situations and should be introduced much sooner in the treatment paradigm of iron-deficient patients. In this chapter, we will review the formulations of IV iron that allow total complete replacement doses in 1 or 2 sessions including practical tips for administration. We realize safety concerns abound and therefo...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

New challenges in evaluating anemia in older persons in the era of molecular testing.
Authors: Steensma DP Abstract Anemia is common in older persons, and often remains unexplained despite a thorough clinical history, physical examination, and focused laboratory testing, including marrow aspiration, biopsy, and karyotyping. The advent of molecular genetic testing panels in hematology clinical practice has complicated the evaluation of older patients with unexplained anemia. While the presence of a somatic mutation provides evidence of clonal hematopoiesis and may support a diagnosis of a hematologic neoplasm such as one of the myelodysplastic syndromes (MDS), with rare exceptions, individual mutatio...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Aplastic anemia and clonal evolution: germ line and somatic genetics.
Authors: Shimamura A Abstract Clonal progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) remains a dreaded complication for a subset of patients with bone marrow failure (BMF). Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germ line and somatic mutations for diagnosing and monitoring patients with BMF. Most ...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Nontransplant therapy for bone marrow failure.
Authors: Townsley DM, Winkler T Abstract Nontransplant therapeutic options for acquired and constitutional aplastic anemia have significantly expanded during the last 5 years. In the future, transplant may be required less frequently. That trilineage hematologic responses could be achieved with the single agent eltrombopag in refractory aplastic anemia promotes new interest in growth factors after years of failed trials using other growth factor agents. Preliminary results adding eltrombopag to immunosuppressive therapy are promising, but long-term follow-up data evaluating clonal evolution rates are required befor...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Transplantation for bone marrow failure: current issues.
Authors: Peffault de Latour R Abstract The preferred treatment of idiopathic aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-identical sibling donor. Transplantation from a well-matched unrelated donor (MUD) may be considered for patients without a sibling donor after failure of immunosuppressive therapy, as may alternative transplantation (mismatched, cord blood or haplo-identical HSCT) for patients without a MUD. HSCT may also be contemplated for congenital disorders in cases of pancytopenia or severe isolated cytopenia. Currently, HSCT aims a...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Biologic vs physiologic age in the transplant candidate.
Authors: Artz AS Abstract Hematopoietic cell transplantation (HCT) remains a cornerstone of treatment of many hematologic malignancies but transplant-associated morbidity and mortality limit application to older patients. Biologic or chronologic age barriers to HCT have fallen, because patients in their 8th decade of life comprise the group with the greatest rise in transplant use over the past decade. Evaluating physiologic age or general health in older transplant candidates requires a systematic approach inclusive of functional and comorbidity assessment, which typically is accomplished through geriatric assessm...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Can we make a better match or mismatch with KIR genotyping?
Authors: Mehta RS, Rezvani K Abstract Natural killer (NK) cell function is regulated by a fine balance between numerous activating and inhibitory receptors, of which killer-cell immunoglobulin-like receptors (KIRs) are among the most polymorphic and comprehensively studied. KIRs allow NK cells to recognize downregulation or the absence of HLA class I molecules on target cells (known as missing-self), a phenomenon that is commonly observed in virally infected cells or cancer cells. Because KIR and HLA genes are located on different chromosomes, in an allogeneic environment such as after hematopoietic stem cell trans...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Role of the intestinal mucosa in acute gastrointestinal GVHD.
Authors: Peled JU, Hanash AM, Jenq RR Abstract Intestinal graft-versus-host disease (GVHD) remains a significant obstacle to the success of allogeneic hematopoietic cell transplantation. The intestinal mucosa comprises the inner lining of the intestinal tract and maintains close proximity with commensal microbes that reside within the intestinal lumen. Recent advances have significantly improved our understanding of the interactions between the intestinal mucosa and the enteric microbiota. Changes in host mucosal tissue and commensals posttransplant have been actively investigated, and provocative insights into muc...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Sequencing of chronic lymphocytic leukemia therapies.
Authors: Barrientos JC Abstract It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in frontline, relapsed, refractory, and high-risk disease. Traditionally, frontline management of CLL has been a combination of chemotherapy (fludarabine, cyclophosphamide, bendamustine, or chlorambucil) with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab). The current landscape is rapidly evolving with the advent of therapies that demonstrate selective inhibition of important pathways necessary for CLL pr...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Novel agents in chronic lymphocytic leukemia.
Authors: Lamanna N, O'Brien S Abstract The advent of novel small-molecule inhibitors has transformed the treatment approaches for patients with chronic lymphocytic leukemia (CLL). These therapies are becoming increasingly used in patients with relapsed disease, patients with 17p deletion, and, as of recently, also in the frontline setting for previously untreated patients with CLL. Moreover, many of these are oral therapies that are significantly less myelosuppressive than chemoimmunotherapy. However, these agents have their own set of unique toxicities with which providers must gain familiarity. There is also ongo...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

First-line therapy for young patients with CLL.
Authors: Jain N, O'Brien S Abstract A 61-year-old man with a history of chronic lymphocytic leukemia (CLL) presents with complaints of worsening fatigue and night sweats. He was diagnosed with CLL 3 years ago on routine blood count testing. He has no major medical comorbidities. On examination, he has several 2- to 3-cm lymph nodes in the cervical and axillary area. Spleen is palpable 5 cm below the costal margin. Blood counts show lymphocytosis with thrombocytopenia and anemia. Prognostic markers include deletion 13q by fluorescence in situ hybridization analysis and mutated IGHV You are asked by the hematology fe...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Prognostication of chronic lymphocytic leukemia in the era of new agents.
Authors: Eichhorst B, Hallek M Abstract The prognosis of chronic lymphocytic leukemia (CLL) is very heterogeneous. Therefore, a plethora of prognostic factors has been identified to allow a better prediction of the individual prognosis of a given patient. The clinical staging systems by Rai and Binet have been the backbone of clinical management for several decades. The advent of genetic and biochemical markers, as well as next-generation sequencing has provided several markers that can predict the prognosis of patients with CLL. Using this knowledge, several scores have been created to improve predicting overall s...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Molecular monitoring in chronic myeloid leukemia-how low can you go?
Authors: Branford S Abstract Molecular monitoring of BCR-ABL1 transcripts for patients with chronic myeloid leukemia (CML) is now used to assess response to tyrosine kinase inhibitors (TKIs), including treatment failure that mandates a change of therapy. Therefore, many centers have adopted the molecular technique for measuring BCR-ABL1 and rely on conversion of values to the international reporting scale for appropriate clinical interpretation. However, the technique has a degree of inherent variability despite standardized procedures, which means care should be taken by the clinician when assessing response based...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Chronic myeloid leukemia: sequencing of TKI therapies.
Authors: Cortes J, Kantarjian H Abstract Multiple tyrosine kinase inhibitors (TKIs) are available for managing patients with chronic myeloid leukemia. Although most patients have a favorable outcome with their initial therapy, whether imatinib or a second-generation TKI was used, some will require subsequent use of one or more different TKIs. Such sequencing might be indicated in a reactive way (ie, for patients who have experienced resistance or intolerance to their initial therapy) or in a proactive way (ie, for patients with a somewhat favorable outcome who have not reached an "optimal" outcome). Seque...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

The value of quality of life assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibitors.
Authors: Efficace F, Cannella L Abstract The development of the oral tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML) is one of the great triumphs of cancer research. Although the efficacy of TKIs has dramatically improved the disease-specific overall survival rate, the prevalence of CML is increasing worldwide. Currently, CML patients receive prolonged (even lifelong) treatment, and over the last decade, clinical decision making has become challenging. Therefore, consideration of the effects of TKI therapies on patients' quality of life (QoL) and symptom burden (ie, patient-reported outcom...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Thrombosis in the setting of obesity or inflammatory bowel disease.
Authors: Lentz SR Abstract Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to wax and wane with disease severity. Because of the lack of high-quality evidence to guide management decisions, approaches to the prevention and treatment of thrombosis in patients with obesity or IBD are based on extrapolation from general guidelines for antithrombotic ther...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Thrombosis and anticoagulation in the setting of renal or liver disease.
Authors: Ribic C, Crowther M Abstract Thrombosis and bleeding are among the most common causes of morbidity and mortality in patients with renal disease or liver disease. The pathophysiology underlying the increased risk for venous thromboembolism and bleeding in these 2 populations is distinct, as are considerations for anticoagulation. Anticoagulation in patients with kidney or liver disease increases the risk of bleeding; this risk is correlated with the degree of impairment of anticoagulant elimination by the kidneys and/or liver. Despite being in the same pharmacologic category, anticoagulant agents may have v...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Thrombosis in the setting of cancer.
Authors: Streiff MB Abstract Venous thromboembolism (VTE) is a common cause of adverse outcomes in patients with cancer. The risk of VTE varies with cancer type, stage and grade, cancer therapy, and supportive care, as well as patient characteristics including age, ethnicity, and inherited and acquired comorbid conditions. VTE prophylaxis should be provided to all hospitalized cancer patients and high-risk outpatients. Low-molecular-weight heparin (LMWH) remains the first-line therapy for VTE in patients with active cancer. Anticoagulation should be continued as long as there is evidence of active disease or patien...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Anti-Xa monitoring of low-molecular-weight heparin in adult patients with cancer.
Authors: Kreuziger LB, Streiff M Abstract A 68-year-old man developed a right femoral vein deep vein thrombosis and bilateral pulmonary embolism while receiving chemotherapy for stage IV prostate cancer. His creatinine at diagnosis is 1.4 mg/dL, with an estimated clearance of 63 mL/min. In patients with cancer, should low-molecular-weight heparin treatment be dosed according to weight, or adjusted using anti-Xa levels? PMID: 27913481 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria.
Authors: Parker CJ Abstract Once suspected, the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) is straightforward when flow cytometric analysis of the peripheral blood reveals a population of glycosyl phosphatidylinositol anchor protein-deficient cells. But PNH is clinically heterogeneous, with some patients having a disease process characterized by florid intravascular, complement-mediated hemolysis, whereas in others, bone marrow failure dominates the clinical picture with modest or even no evidence of hemolysis observed. The clinical heterogeneity is due to the close, though incompletely understood, rela...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Atypical hemolytic uremic syndrome.
Authors: Afshar-Kharghan V Abstract Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) that affects multiple organs and the kidneys in particular. aHUS can be sporadic or familial and is most commonly caused by dysregulation of the alternative complement pathway. The initial attack of aHUS can occur at any age, and is associated with a high rate of progression to end stage renal disease. Many aHUS patients relapse in the native or transplanted kidneys, and require close monitoring and long-term management. Availability of anticomplement therapy has revolutionized the management of aHUS,...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Cold agglutinin disease.
Authors: Berentsen S Abstract Primary chronic cold agglutinin disease (CAD) is a well-defined clinicopathologic entity in which a specific, clonal lymphoproliferative B-cell bone marrow disorder results in autoimmune hemolytic anemia. The immune hemolysis is entirely complement-dependent, predominantly mediated by activation of the classical pathway and phagocytosis of erythrocytes opsonized with complement protein C3b. Typical clinical features in CAD have diagnostic and therapeutic implications. Pharmacologic treatment should be offered to patients with symptom-producing anemia or disabling circulatory symptoms. ...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Congenital and acquired bleeding disorders in pregnancy.
Authors: Gernsheimer TB Abstract Obstetrical hematology represents challenges not only for the patient, but also for her progeny. In particular, bleeding disorders, both congenital and acquired, not only present problems both for delivery and in the immediate postpartum period, but also may have significant implications for the fetus and neonate. Women with congenital bleeding disorders or who are carriers of X-linked or autosomal disorders should be counseled prior to conception so that pregnancy can be safely undertaken with careful preparation. A treatment plan should be set up by a specialized care team that in...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Heavy menstrual bleeding: work-up and management.
Authors: James AH Abstract Heavy menstrual bleeding (HMB), which is the preferred term for menorrhagia, affects ∼90% of women with an underlying bleeding disorder and ∼70% of women on anticoagulation. HMB can be predicted on the basis of clots of ≥1 inch diameter, low ferritin, and "flooding" (a change of pad or tampon more frequently than hourly). The goal of the work-up is to determine whether there is a uterine/endometrial cause, a disorder of ovulation, or a disorder of coagulation. HMB manifest by flooding and/or prolonged menses, or HMB accompanied by a personal or family history of bleed...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Venous thromboembolism and stroke in pregnancy.
Authors: McLean K, Cushman M Abstract Pregnancy and the postpartum period substantially increase the risk for thrombotic events. Although the absolute risk for thrombosis is low, these events comprise a significant portion of maternal morbidity and mortality. The vast majority of such events are venous, although the risk for ischemic stroke also appears to be increased in pregnancy. This review will explore the overlapping and unique risk factors for venous and arterial thrombosis in pregnancy. Diagnosis and prevention will be discussed, and treatment will be briefly touched on. The benefit of using a multidiscipli...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Platelets in liver and renal disease.
Authors: Lambert MP Abstract This review will discuss how 2 common and morbid conditions, renal disease and liver disease, alter platelet number and function. It will review the impact of thrombocytopenia on bleeding complications in patients with these disorders and whether the low platelet count actually correlates with bleeding risk. Emerging data also suggest that platelets are much more than bystanders in both renal and liver disease, but instead play an active role in the pathobiology of these disorders. This review will briefly cover the emerging information on novel roles of platelets in the biology of rena...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Platelets in infectious disease.
Authors: Middleton E, Rondina MT Abstract Sepsis is a dynamic, acute, infectious disease syndrome characterized by dysregulated thrombo-inflammatory responses. The high mortality associated with sepsis has been recognized since the earliest clinicians' writings. Despite this, advances in the treatment of sepsis have been more modest. This is limited, in part, by the heterogeneity in the definition, population, presentation, and causal factors of infectious syndromes. Given the persistently high morbidity and mortality associated with sepsis, a better understanding of the dysregulated cellular biology underpinning s...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Heparin-induced thrombocytopenia: research and clinical updates.
Authors: Onwuemene O, Arepally GM Abstract Heparin-induced thrombocytopenia (HIT) remains an important diagnosis to consider in hospitalized patients developing thrombocytopenia. HIT is an immune-mediated prothrombotic disorder caused by antibodies to platelet factor 4 (PF4) and heparin. Recent basic scientific studies have advanced our understanding of disease pathogenesis through studies of the PF4/heparin structure, immune mechanisms, and cellular basis of thrombosis. Clinical advances have also occurred in areas of HIT prevention, description of disease variants, and diagnostic strategies. Emerging anticoagulan...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Prognostic factors in follicular lymphoma: new tools to personalize risk.
Authors: Casulo C Abstract Follicular lymphoma (FL) is the most common indolent lymphoma, and it has a long median overall survival (OS). However, the recent discovery of clinical and biological prognostic biomarkers in FL is shedding light on FL heterogeneity and the need for a precise and risk-stratified individual approach at diagnosis and relapse. Many FL patients who are asymptomatic with indolent disease can be vulnerable to the toxicity, emotional distress, and financial burden of overtreatment. Yet a subset of FL patients develop chemoresistance to standard chemoimmunotherapy, experience transformation to a...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Frontline strategy for follicular lymphoma: are we ready to abandon chemotherapy?
Authors: Fowler N Abstract Chemotherapy combinations have been the backbone of therapy for follicular lymphoma, and are associated with high initial response rates. Unfortunately, toxicity and secondary malignancies remain concerns, and most advanced-stage patients still relapse within 5 years, regardless of the regimen. Advances in the understanding of lymphoma biology have resulted in a new generation of noncytotoxic therapeutics with significant activity in follicular lymphoma. Recent studies exploring biological and targeted combinations in the frontline have shown promise, with response rates similar to chemot...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Novel agents in follicular lymphoma: choosing the best target.
Authors: Sehn LH Abstract Outcomes in patients with follicular lymphoma (FL) have improved dramatically over the last decade. However, novel agents are greatly needed for those who exhibit treatment resistance, in order to minimize lifelong toxicity and to enable combinations that may allow us to achieve the elusive goal of cure. Biological advances have led to the discovery of a large number of potential therapeutic targets and the development of a plethora of novel agents designed to exploit these processes. Possible targets include tumor cell surface markers, key components of intracellular pathways and epigenet...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Introduction to cancer genetic susceptibility syndromes.
Authors: McGee RB, Nichols KE Abstract The last 30 years have witnessed tremendous advances in our understanding of the cancer genetic susceptibility syndromes, including those that predispose to hematopoietic malignancies. The identification and characterization of families affected by these syndromes is enhancing our knowledge of the oncologic and nononcologic manifestations associated with predisposing germ line mutations and providing insights into the underlying disease mechanisms. Here, we provide an overview of the cancer genetic susceptibility syndromes, focusing on aspects relevant to the evaluation of pat...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Germ line mutations associated with leukemias.
Authors: Porter CC Abstract Several genetic syndromes have long been associated with a predisposition to the development of leukemia, including bone marrow failure syndromes, Down syndrome, and Li Fraumeni syndrome. Recent work has better defined the leukemia risk and outcomes in these syndromes. Also, in the last several years, a number of other germ line mutations have been discovered to define new leukemia predisposition syndromes, including ANKRD26, GATA2, PAX5, ETV6, and DDX41 In addition, data suggest that a substantial proportion of patients with therapy related leukemias harbor germ line mutations in DNA da...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Discussing and managing hematologic germ line variants.
This article covers some of the issues related to the diagnosis and interpretation of variants associated with hereditary hematologic malignancies, including the importance of an accurate family history in interpreting genetic variants associated with disease. The challenges of screening other family members and offering the most appropriate early malignancy detection is also discussed. We now have a good opportunity to better define hereditary cancer syndromes with associated hematologic malignancies and contribute to clinically effective guidelines. PMID: 27913496 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Response-adapted frontline therapy for Hodgkin lymphoma: are we there yet?
Authors: Johnson PW Abstract Treating Hodgkin lymphoma by using chemotherapy with or without radiotherapy is highly successful, with substantially fewer deaths from lymphoma than from other causes in recent studies of both early-stage and advanced-stage disease. Long-term toxicity is a major consideration in this context, and recent trials have used functional imaging with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography early in the course of treatment (interim PET) to assess response and modulate subsequent therapy. In early-stage disease, this has allowed omission of consolidation radiotherapy after ...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment.
Authors: van Leeuwen FE, Ng AK Abstract Long-term survivors of Hodgkin lymphoma (HL) experience several late adverse effects of treatment, with second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) being the leading causes of death in these patients. Other late effects have also been identified, such as pulmonary dysfunction, endocrinopathies (thyroid dysfunction, infertility), neck muscle atrophy, and persistent fatigue. HL survivors have two- to fourfold increased risks to develop SMNs and CVD compared with the general population. With respect to SMNs, radiotherapy is associated with 1.5- to 15-fol...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Novel agents and strategies in transplant-eligible patients with relapsed and refractory Hodgkin lymphoma.
Authors: Moskowitz C Abstract The majority of patients with Hodgkin lymphoma are cured with frontline therapy; however, 10% to 15% with early-stage disease and 20% to 30% with advanced stage require second-line therapy that includes a potentially curative transplant, of which an additional 50% to 55% are cured. Those with multiply relapsed disease traditionally would receive novel agents on a clinical trial or combination chemotherapy as a potential bridge to an allogeneic stem cell transplant. This treatment paradigm has changed with the availability of brentuximab vedotin, an antibody drug conjugate used pre- and...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction.
Authors: Rao AV Abstract Acute myeloid leukemia (AML) is a disease of the elderly, but less than half of these patients are offered therapy despite the evidence of better survival with treatment in this patient population. Assessing fit, vulnerable, and frail older adults with AML remains a challenge for the treating oncologist. A majority of AML patients are elderly and often have significant comorbidities, lack of social support, and older caregivers. Performance status (PS), a subjective measure of how a patient will tolerate cancer chemotherapy, has been strongly correlated with mortality in older AML patients....
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Mutations in AML: prognostic and therapeutic implications.
Authors: DiNardo CD, Cortes JE Abstract Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the proliferation and aberrant differentiation of immature clonal myeloid cells. The prognosis of AML is variable, based on clinical features such as patient age, performance status, and comorbidities, as well as leukemia-specific genetic features including cytogenetics and molecular classification. The modern application of next-generation sequencing technology has uncovered marked heterogeneity and genomic complexity within AML, based on the presence or absence of cooperating mutations w...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

MRD in AML: does it already guide therapy decision-making?
Authors: Ossenkoppele G, Schuurhuis GJ Abstract Prognostic factors determined at diagnosis are predictive for outcome whereas achievement of morphological complete remission (CR) is still an important end point during treatment. Residual disease after therapy may reflect the sum of all diagnosis and postdiagnosis resistance mechanisms/factors; its measurement could hypothetically be very instrumental for guiding treatment. The possibility of defining residual disease (minimal residual disease [MRD]) far below the level of 5% blast cells is changing the landscape of risk classification. In this manuscript, the vario...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Diffuse large B-cell lymphoma: R-CHOP failure-what to do?
Authors: Coiffier B, Sarkozy C Abstract Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL), ∼30% to 50% of patients are not cured by this treatment, depending on disease stage or prognostic index. Among patients for whom R-CHOP therapy fails, 20% suffer from primary refractory disease (progress during or right after treatment) whereas 30% relapse after achieving complete remission (CR). Currently, there is no good definition enabling us to identify these 2 groups upon diagnosis. Most of the...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Primary central nervous system lymphoma.
Authors: Batchelor TT Abstract Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma (NHL) confined to the brain, leptomeninges, eyes, or spinal cord. The majority of PCNSL cases occur in the immunocompetent host, the focus of this review. The prognosis of PCNSL is inferior to that of other NHL subtypes including other organ-specific subtypes of extranodal NHL. The 5- and 10-year survival proportions for PCNSL are 29.3% and 21.6%, respectively. The diagnosis and management of PCNSL differs from that of other primary brain cancers and NHL in other parts of the body. PMID: 27913504...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research