Showing papers in "Hematology-oncology Clinics of North America in 2016"
TL;DR: This work estimated levels and trends of nonfatal anemia burden for 23 distinct etiologies in 188 countries, 20 age groups, and both sexes from 1990 to 2013 using the approach of the Global Burden of Disease, Injuries and Risk Factors 2013 Study.
Abstract: Anemia is an important cause of health loss. We estimated levels and trends of nonfatal anemia burden for 23 distinct etiologies in 188 countries, 20 age groups, and both sexes from 1990 to 2013. All available population-level anemia data were collected and standardized. We estimated mean hemoglobin, prevalence of anemia by severity, quantitative disability owing to anemia, and underlying etiology for each population using the approach of the Global Burden of Disease, Injuries and Risk Factors 2013 Study. Anemia burden is high. Developing countries account for 89% of all anemia-related disability. Iron-deficiency anemia remains the dominant cause of anemia.
469 citations
TL;DR: G6PD deficiency, one of the commonest inherited enzyme abnormalities in humans, arises through one of many possible mutations, most of which reduce the stability of the enzyme and its level as red cells age.
Abstract: G6PD is a housekeeping gene expressed in all cells. Glucose-6-phosphate dehydrogenase (G6PD) is part of the pentose phosphate pathway, and its main physiologic role is to provide NADPH. G6PD deficiency, one of the commonest inherited enzyme abnormalities in humans, arises through one of many possible mutations, most of which reduce the stability of the enzyme and its level as red cells age. G6PD-deficient persons are mostly asymptomatic, but they can develop severe jaundice during the neonatal period and acute hemolytic anemia when they ingest fava beans or when they are exposed to certain infections or drugs. G6PD deficiency is a global health issue.
244 citations
TL;DR: The inherited genetics, diagnosis, and treatment of PCCs and PGLs are reviewed, which can offer limited tumor and hormone control, although none are curative.
Abstract: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare but unique neuroendocrine tumors. The hypersecretion of catecholamines from the tumors can be associated with high morbidity and mortality, even when tumors are benign. Up to 40% of PCCs/PGLs are associated with germline mutations in susceptibility genes. About one-quarter are malignant, defined by the presence of distant metastases. Treatment options for unresectable metastatic disease, including chemotherapy, (131)I-MIBG, and radiation, can offer limited tumor and hormone control, although none are curative. This article reviews the inherited genetics, diagnosis, and treatment of PCCs and PGLs.
117 citations
TL;DR: Peptide receptor radionuclide therapy is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors patients and progression-free and overall survival compare favorably with that for somatostatin analogues, chemotherapy, or newer, "targeted" therapies.
Abstract: Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors patients. Most studies report objective response rates in 15% to 35% of patients. Progression-free (PFS) and overall survival (OS) compare favorably with that for somatostatin analogues, chemotherapy, or newer, "targeted" therapies. Prospective, randomized data regarding the potential PFS and OS benefit of PRRT compared with standard therapies is anticipated.
105 citations
TL;DR: This review addresses RBC transfusion methods, evidence-based and/or expert panel-based consensus on indications for chronic and episodic transfusion indications, and strategies to prevent and manage transfusion-related complications.
Abstract: Red blood cell (RBC) transfusion therapy is a key component of comprehensive management of patients with sickle cell disease (SCD) and has increased over time as a means of primary and secondary stroke prevention. RBC transfusions also prove to be lifesaving for many acute sickle cell-related complications. Although episodic and chronic transfusion therapy has significantly improved the morbidity and mortality of patients with SCD, transfusions are not without adverse effects. This review addresses RBC transfusion methods, evidence-based and/or expert panel-based consensus on indications for chronic and episodic transfusion indications, and strategies to prevent and manage transfusion-related complications.
79 citations
TL;DR: Greater investments in basic and applied research in the African context, and increased sensitization or African ministries of health regarding the importance of this condition, could make a substantial difference to the lives and livelihoods of millions of people living with sickle cell disease on the continent and their families.
Abstract: In Africa, at least 240,000 children are born each year with sickle cell disease. Historically, in the absence of newborn screening and appropriate treatment, most such children died undiagnosed in early childhood. However, with increasing awareness of the condition and economic and epidemiologic transition, increasing numbers are surviving. Greater investments in basic and applied research in the African context, and increased sensitization or African ministries of health regarding the importance of this condition, could make a substantial difference to the lives and livelihoods of millions of people living with sickle cell disease on the continent and their families.
66 citations
TL;DR: In this article, a brief description of the main inherited disorders of hemoglobin and their classification, and summarizes progress made in the last decade toward a better awareness and recognition of these disorders as a global health problem are presented.
Abstract: The inherited disorders of hemoglobin represent the most common monogenic diseases. This article provides a brief description of the main inherited disorders of hemoglobin and their classification, and summarizes progress made in the last decade toward a better awareness and recognition of these disorders as a global health problem. Also presented are the main demographic, genetic, and environmental factors that influence the present and future health burden of these disorders. The strengths and limitations of existing estimates and current health policies in high-, low-, and middle-income countries are discussed.
61 citations
TL;DR: There has been recent success developing intermediate intensity approaches that are well tolerated in all patient groups and maintain high cure rates in a multicenter setting.
Abstract: Because of its rarity and high curability, progress in advancing therapeutics in Burkitt lymphoma (BL) has been difficult. Over recent years, several new mutations that cooperate with MYC have been identified, and this has paved the way for testing novel agents in the disease. One of the challenges of most standard approaches typically used is severe treatment-related toxicity that often leads to discontinuation of therapy. To that point, there has been recent success developing intermediate intensity approaches that are well tolerated in all patient groups and maintain high cure rates in a multicenter setting.
53 citations
TL;DR: The different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed.
Abstract: Neuroendocrine tumors (NETs) are slow-growing neoplasms capable of storing and secreting different peptides and neuroamines. Some of these substances cause specific symptom complexes, whereas others are silent. They usually have episodic expression, and the diagnosis is often made at a late stage. Although considered rare, the incidence of NETs is increasing. For these reasons, a high index of suspicion is needed. In this article, the different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed.
52 citations
TL;DR: At least in children, iron supplementation exacerbates the risk of infection in both malaria-endemic and nonendemic low-income countries, whereas iron deficiency is protective against clinical and severe malaria.
Abstract: Anemia is common among people living in low- and middle-income countries, and alleviation of the global burden of anemia is an essential global health target over the next decade. Estimates have attributed about half the cases of anemia worldwide to iron deficiency; a range of other causes probably make a similar overall contribution. Individuals living in low-income settings experience a simultaneous high burden of infection with inflammation and iron deficiency. At least in children, iron supplementation exacerbates the risk of infection in both malaria-endemic and nonendemic low-income countries, whereas iron deficiency is protective against clinical and severe malaria.
50 citations
TL;DR: The contributions of components of the intrinsic pathway to thrombosis in animal models and humans, and results of early clinical trials of drugs targeting factors IX, XI, and XII are discussed.
Abstract: Plasma coagulation in the activated partial thromboplastin time assay is initiated by sequential activation of coagulation factors XII, XI, and IX. While this series of proteolytic reactions is not an accurate model for hemostasis in vivo, there is mounting evidence that factor XI and factor XII contribute to thrombosis, and that inhibiting them can produce an antithrombotic effect with a small effect on hemostasis. This article discusses the contributions of components of the intrinsic pathway to thrombosis in animal models and humans, and results of early clinical trials of drugs targeting factors IX, XI, and XII.
TL;DR: This review summarizes the current approach to the diagnosis, classification, grading, and therapeutic stratification of neuroendocrine neoplasms, with a focus on those arising in the lung and thymus, pancreas, and intestines.
Abstract: The pathologic classification of neuroendocrine neoplasms has evolved over the past decades, as new understanding of the biological behavior, histologic characteristics, and genetic features have emerged. Nonetheless, many aspects of the classification systems remain confusing or controversial. Despite these difficulties, much progress has been made in determining the features predicting behavior. Genetic findings have helped establish relationships among different types of neuroendocrine neoplasms and revealed potential therapeutic targets. This review summarizes the current approach to the diagnosis, classification, grading, and therapeutic stratification of neuroendocrine neoplasms, with a focus on those arising in the lung and thymus, pancreas, and intestines.
TL;DR: The problems in supply, safety, and use of blood and how they are being addressed in LMICs are examined, predominantly focusing on sub-Saharan Africa.
Abstract: A safe supply of blood and the knowledge, skill, and resources for the appropriate use of blood are essential for medical services. Many problems are faced in the development of transfusion services in low- or medium-income countries (LMICs). Unfortunately, in many countries, providing safe blood is made more difficult by a lack of blood donors and the high frequency of transfusion-transmissible infections. The problems are compounded by the frequent need for urgent life-saving transfusions. This article examines the problems in supply, safety, and use of blood and how they are being addressed in LMICs, predominantly focusing on sub-Saharan Africa.
TL;DR: It is vital that the global health importance of the thalassemias and related disorders, by far the commonest genetic diseases, is emphasized to the appropriate international health agencies.
Abstract: Because of the particularly high frequency of different severe forms of both α and β thalassemia in Asia, the development of approaches for their prevention and management is particularly challenging. However, because of earlier partnerships with richer countries, so-called North/South partnerships, and help from their governments, considerable progress toward the better control of the thalassemias has been achieved in some countries. It is vital that the global health importance of the thalassemias and related disorders, by far the commonest genetic diseases, is emphasized to the appropriate international health agencies.
TL;DR: Immune-mediated platelet refractoriness is suggested when a 10-minute to 1-hour corrected count increment of less than 5 × 10(9)/L is observed after 2 sequential transfusions using ABO-identical, freshest available platelets.
Abstract: Platelet refractoriness occurs when there is an inadequate response to platelet transfusions, which typically has nonimmune causes, but is also associated with alloantibodies to human leukocyte antigens (HLAs) and/or human platelet antigens. Immune-mediated platelet refractoriness is suggested when a 10-minute to 1-hour corrected count increment of less than 5 × 10(9)/L is observed after 2 sequential transfusions using ABO-identical, freshest available platelets. When these antibodies are identified, one of 3 strategies should be used for identifying compatible platelet units: HLA matching, crossmatching, and antibody specificity prediction. These strategies seem to offer similar results in terms of posttransfusion platelet increments.
TL;DR: An accumulation of insights into the molecular and cellular basis of disease pathogenesis is providing a foundation for the generation of molecular tools to facilitate diagnosis as well as a roadmap for integration of targeted therapy within the developing therapeutic armamentarium for this challenging brain tumor.
Abstract: Primary central nervous system (CNS) lymphoma is a challenging subtypes of aggressive non-Hodgkin lymphoma. Emerging clinical data suggest that optimized outcomes are achieved with dose-intensive CNS-penetrant chemotherapy and avoiding whole brain radiotherapy. Anti-CD20 antibody-based immunotherapy as a component of high-dose methotrexate-based induction programs may contribute to improved outcomes. An accumulation of insights into the molecular and cellular basis of disease pathogenesis is providing a foundation for the generation of molecular tools to facilitate diagnosis as well as a roadmap for integration of targeted therapy within the developing therapeutic armamentarium for this challenging brain tumor.
TL;DR: The use of pathogen inactivation causes a decrease in the parameters of products that can be readily measured in laboratory assays but that do not seem to cause any alteration in hemostatic effect of plasma or platelet transfusions as discussed by the authors.
Abstract: Pathogen inactivation technologies represent a shift in blood safety from a reactive approach to a proactive protective strategy. Commercially available technologies demonstrate effective killing of most viruses, bacteria, and parasites and are capable of inactivating passenger leukocytes in blood products. The use of pathogen inactivation causes a decrease in the parameters of products that can be readily measured in laboratory assays but that do not seem to cause any alteration in hemostatic effect of plasma or platelet transfusions. Effort needs to be made to further develop these technologies so that the negative quality impact is ameliorated without reducing the pathogen inactivation effectiveness.
TL;DR: Primary central nervous system lymphoma (PCNSL) is a rare aggressive high-grade type of extranodal lymphoma that can mimic other brain disorders such as encephalitis, demyelination, and stroke.
Abstract: Primary central nervous system lymphoma (PCNSL) is a rare aggressive high-grade type of extranodal lymphoma. PCNSL can have a variable imaging appearance and can mimic other brain disorders such as encephalitis, demyelination, and stroke. In addition to PCNSL, the CNS can be secondarily involved by systemic lymphoma. Computed tomography and conventional MRI are the initial imaging modalities to evaluate these lesions. Recently, however, advanced MRI techniques are more often used in an effort to narrow the differential diagnosis and potentially inform diagnostic and therapeutic decisions.
TL;DR: Immunohematologic tests are reviewed, how autoimmune hemolytic anemia is classified by autoantibodies is described, and RBC alloimmunization rates are outlined, and strategies to prevent/mitigate the impact of RBCAlloIMmunization are presented.
Abstract: Red blood cell (RBC) transfusion is a cornerstone of the management of patients with hematology/oncology disorders. However, a potentially deleterious consequence of transfusion is the development of alloantibodies against blood group antigens present on RBCs. Such alloantibodies can be an obstacle in providing compatible units for transfusion. Providers in this arena must fully understand the testing performed by blood banks, as well as the consequences of detected antibodies. This article reviews immunohematologic tests, describes how autoimmune hemolytic anemia is classified by autoantibodies; outlines RBC alloimmunization rates, and presents strategies to prevent/mitigate the impact of RBC alloimmunization.
TL;DR: Liver resection has excellent survival rates even in the event of an incomplete resection, as well as improvement in hormonal symptoms, and radiofrequency ablation can help to preserve hepatic parenchyma during resection.
Abstract: Neuroendocrine tumors of the small bowel are rare, slow-growing malignancies that commonly metastasize to nodes at the root of the mesentery and the liver. Liver metastases are associated with carcinoid syndrome. Mesenteric nodal masses can cause bowel obstruction, intestinal angina, or variceal hemorrhage. Patients die of liver failure or bowel obstruction. Primary resection is associated with improved survival rates. Selected patients may benefit from liver debulking operations. Liver resection has excellent survival rates even in the event of an incomplete resection, as well as improvement in hormonal symptoms. Radiofrequency ablation can help to preserve hepatic parenchyma during resection.
TL;DR: The most common bone malignancy is multiple myeloma and related plasma cell proliferative disorders have a diverse set of clinicopathologic findings and on neuroimaging present unique and diverse findings from the disease and from complications of the disease as discussed by the authors.
Abstract: Multiple myeloma is the most common bone malignancy. Imaging plays an important role in identifying the extent of the disease, disease process, guiding biopsies, and diagnosing associated spinal and intracranial complications. Multiple myeloma and related plasma cell proliferative disorders have a diverse set of clinicopathologic findings and on neuroimaging present unique and diverse findings from the disease and from complications of the disease and treatment, which are valuable for clinicians and radiologists.
TL;DR: Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors with a range of clinical behavior, and surgical resection is the mainstay of therapy, particularly for localized disease.
Abstract: Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors with a range of clinical behavior. Some PNETs are associated with symptoms of hormone secretion, with increased systemic levels of insulin, gastrin, glucagon, or other hormones. More commonly, PNETs are nonfunctional, without hormone secretion. Surgical resection is the mainstay of therapy, particularly for localized disease. Surgical therapy must be tailored to tumor and clinical characteristics. Resection may be particularly indicated in the setting of hormone hypersecretion. Small, incidental PNETs are increasingly managed nonoperatively. Surgery may also be indicated in some instances of metastatic disease, if all metastatic foci may be removed.
TL;DR: Peripheral blood stem cell collection is an effective approach to obtain a hematopoietic graft for stem cell transplantation and technological advance and innovations in leukapheresis have improved collection efficiency and reduced adverse effects.
Abstract: Peripheral blood stem cell collection is an effective approach to obtain a hematopoietic graft for stem cell transplantation. Developing hematopoietic stem/progenitor cell (HSPC) mobilization methods and collection algorithms have improved efficiency, clinical outcomes, and cost effectiveness. Differences in mobilization mechanisms may change the HSPC content harvested and result in different engraftment kinetics and complications. Patient-specific factors can affect mobilization. Incorporating these factors in collection algorithms and improving assays for evaluating mobilization further extend the ability to obtain sufficient HSPCs for hematopoietic repopulation. Technological advance and innovations in leukapheresis have improved collection efficiency and reduced adverse effects.
TL;DR: The role of SSAs in the treatment of NETs is reviewed, suggesting peptide receptor radionuclide therapy with radiolabeled SSAs is a new, promising treatment for inoperable or metastatic NETs.
Abstract: Neuroendocrine tumors (NETs) are rare epithelial neoplasms with neuroendocrine differentiation originating most commonly in the lungs and gastroenteropancreatic. Treatment includes surgery and other local therapies; treatment of inoperable disease centers around symptom management and control of tumor growth. Somatostatin analogues (SSAs) have been a mainstay of managing hormone-related symptoms. Emerging evidence suggests that they are effective therapies for tumor control also. Peptide receptor radionuclide therapy with radiolabeled SSAs is a new, promising treatment for inoperable or metastatic NETs. This article reviews the role of SSAs in the treatment of NETs.
TL;DR: Intra-arterial hepatic-directed therapies for metastases from NETs, a group of treatments in which the therapeutic and/or embolic agents are released intra-arterially in specific hepatic vessels to target tumors, are described.
Abstract: Neuroendocrine tumors (NETs) of the gastrointestinal (GI) tract have a propensity for producing hepatic metastases. Most GI NETs arise from the foregut or midgut, are malignant, and can cause severe debilitating symptoms adversely affecting quality of life. Aggressive treatments to reduce symptoms have an important role in therapy. Patients with GI NETs usually present with inoperable metastatic disease and severe symptoms from a variety of hormones and biogenic amines. This article describes intra-arterial hepatic-directed therapies for metastases from NETs, a group of treatments in which the therapeutic and/or embolic agents are released intra-arterially in specific hepatic vessels to target tumors.
TL;DR: The article provides a schematic description of how molecularly defined DLBCL subtypes could guide tailored therapy and discusses the advantages and drawbacks of the currently available techniques of DLBCl subtype determination.
Abstract: Major progress in the understanding of diffuse large B-cell lymphoma (DLBCL) biology has been made in the last decade. Many specific compounds have now entered early phase clinical trials. However, further efforts are needed to find an accurate, fast, reproducible, and affordable technique to translate DLBCL subtype determination by gene expression profiles into clinical application. This article discusses the advantages and drawbacks of the currently available techniques of DLBCL subtype determination as well as important prognostic implications related to the cell of origin. Furthermore, the article provides a schematic description of how molecularly defined DLBCL subtypes could guide tailored therapy.
TL;DR: Second-line therapy options for patients with DLBCL refractory to 2 lines of therapy have a very poor prognosis and generally short survival, and should be carefully considered for participation in clinical trials of novel approaches.
Abstract: Second-line therapy options for patients with diffuse large B-cell lymphoma (DLBCL) that is refractory to, or relapses after, current rituximab-containing primary therapy continue to evolve. For younger patients, salvage therapy followed by intensive therapy and autologous stem cell transplant (ASCT) remains the treatment of choice for those with chemotherapy-sensitive disease. Combination therapy may be used for those who are not candidates for ASCT. In contrast, patients with DLBCL refractory to 2 lines of therapy have a very poor prognosis and generally short survival, and should be carefully considered for participation in clinical trials of novel approaches.
TL;DR: The available systemic therapy options for advanced pancreatic neuroendocrine tumors are reviewed, including somatostatin analogues, a select group of cytotoxic chemotherapy agents, and targeted or biological agents.
Abstract: Pancreatic neuroendocrine tumors are an uncommon tumor type and compose 1% to 2% of all pancreatic neoplasms. They are rarely localized at presentation and are typically diagnosed in the presence of metastatic disease. The management poses a significant challenge because of the heterogeneous clinical presentations and varying degrees of aggressiveness. A variety of systemic therapies have been developed for the management of pancreatic neuroendocrine tumors, including somatostatin analogues, a select group of cytotoxic chemotherapy agents, and targeted or biological agents. This article reviews the available systemic therapy options for advanced pancreatic neuroendocrine tumors.
TL;DR: An overview of AF is provided, basic properties of NOACs are summarized, current data on use in special populations and specific clinical scenarios are presented, and recommendations from experts on controversial topics of bleeding management and reversal are described.
Abstract: For more than 50 years, vitamin K antagonists (VKAs) have been the standard of care for treatment of atrial fibrillation (AF). However, the numerous limitations of VKAs have led to the development of non-VKA oral anticoagulants (NOACs). There are 4 NOACs currently approved for prevention of thromboembolism in patients with nonvalvular AF. This article provides an overview of AF, summarizes basic properties of NOACs, and reviews the landmark trials. Current data on use of NOACs in special populations and specific clinical scenarios are also presented. Lastly, recommendations from experts on controversial topics of bleeding management and reversal are described.
TL;DR: The approach to bronchial and thymic carcinoid patients is discussed, from the initial diagnosis and evaluations to treatment, and many treatment strategies that have been demonstrated in gastrointestinal and pancreatic neuroendocrine tumors are used.
Abstract: Bronchial and thymic carcinoids are rare. We present epidemiologic data and potential risk factors. The approach to bronchial and thymic carcinoid patients is discussed, from the initial diagnosis and evaluations to treatment. These malignancies follow staging systems of their site of origin. Because bronchial and thymic carcinoids are rare, we use many treatment strategies that have been demonstrated in gastrointestinal and pancreatic neuroendocrine tumors. The lack of information regarding efficacy in bronchial and thymic carcinoids, as well as the scarcity of therapeutic options available, demands the importance of clinical trials that include these patients.