bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal Gammopathy of Undetermined Significance and Smoldering Myeloma: New Insights into Pathophysiology and Epidemiology
Authors: Landgren Ola 
Published: January 2011

AbstractRoutine screening for monoclonal gammopathy of undetermined significance (MGUS) is not indicated. Despite this fact, MGUS is a common finding in medical practice. Almost all individuals diagnosed with MGUS represent incidental cases diagnosed when physicians order serum protein electrophoresis, immunofixation, or both, as part of the work-up of a number of common symptoms and laboratory abnormalities. In the absence of reliable molecular predictors of outcome, the detection of an early precursor state typically imposes a complex situation for the patient and the responsible physician—usually, it leads to a lot of questions that lack clear answers. In the past years, several novel insights have been gained in the area of multiple myeloma (MM) precursor disease. This review focuses on results from recent investigations and discusses implications for diagnostic work-up, clinical management, and patient counseling. More specifically, it sheds light on the following commonly asked questions by patients and physicians: i) what is the risk of progression from precursor to full-blown MM, and are there ways to risk-stratify patients?; ii) is MM always preceded by a precursor state, and is there anything that could or should be done to delay or prevent progression?; and iii) why do some individuals develop MM precursor diseases, and is there a reason to screen the family?
Telomere Biology and Telomere Diseases: Implications for Practice and Research
Authors: Young Neal S. 
Published: January 2011

Abstract
The recent recognition of genetic defects in telomeres and telomere repair in multiple human diseases has practical implications for hematologists and oncologists and their patients; consequences for future clinical research in hematology and other subspecialties; and even importance in the interpretation of animal experiments involving cell propagation. Telomere diseases include constitutional marrow failure as dyskeratosis congenita, some apparently acquired aplastic anemia, myelodysplasia and acute myeloid leukemia; pulmonary fibrosis; and hepatic nodular regenerative hyperplasia and cirrhosis. Accelerated telomere attrition is a likely pathophysiology of cancer arising from chronic inflammation. Telomerase can be modulated by sex hormones, which may explain the activity of androgens in marrow failure. Measurement of telomere length of peripheral blood leukocytes is a simple screening clinical assay. Detection of a mutation in a patient has implications for therapy, prognosis, monitoring, and genetic counseling. For research in hematology and oncology, telomere biology could be assessed as a risk for secondary malignancies and in graft-versus-host disease, for progression in a variety of blood cancers, and as potentially modifiable by hormone replacement strategies.
Relapsed Multiple Myeloma
Authors: Lonial Sagar 
Published: January 2011

Abstract
Advances in treatment options for patients with multiple myeloma have made a significant impact on the overall survival of patients and have helped achieve levels of response and duration of remission previously not achievable with standard chemotherapy-based approaches. These improvements are due, in large part, to the development of the novel agents thalidomide, bortezomib, and lenalidomide, each of which has substantial single-agent activity. In addition, a large number of second-generation agents are also in clinical development, such that the repertoire of available treatment options continues to expand. To better interpret clinical trials performed in the relapsed setting, it is important that definitions of relapse categories are used to help better pinpoint the specific benefit for a given therapy, especially in the combination therapy setting as it aids in determining if ongoing work should be continued or abandoned for a given new agent. Insights from preclinical modeling and in vitro work have identified several new combinations, new targets and second- or third-generation versions of existing targets that hold great promise in the setting of relapsed myeloma. Combinations of thalidomide, bortezomib, and lenalidomide with conventional agents or among each other have resulted in enhanced response rates and efficacy. Clinical trials of agents such as carfilzomib, pomalidomide, vorinostat, panobinostat, and elotuzomab are just a few of the many exciting new compounds that are being tested in phase 1 and phase 2 clinical trials for relapsed patients. Further clinical and translational testing are critical to better understanding how best to combine these new agents, as well as identifying patient populations that may best benefit from treatment with these developing new agents.
How Much? How Frequent? How Long? A Clinical Guide to New Therapies in Myelodysplastic Syndromes
Authors: Blum William 
Published: January 2011

AbstractAdvances in the treatment of myelodysplastic syndromes (MDSs) over the last decade have given patients and their hematologists a multitude of treatment options. Therapeutic options now exist that reduce disease-related symptoms, improve quality of life, and alter the natural history of the disease. Three drugs are now specifically Food and Drug Administration-approved for treatment of MDS: (1) azacitidine, (2) decitabine, and (3) lenalidomide. Clinical results with each of these agents, plus results with immunosuppressive therapy, are reviewed to guide clinical decision making. Although each therapy has made a substantial impact in improving the care of patients with MDS, unfortunately MDS treatment in 2010 ultimately fails in most patients, but these therapies provide a foundation on which we can build to further improve outcomes.
Evidence-Based Mini-Review: Should Patients Over the Age of 60 with INT-2 or High-Risk Myelodysplastic Syndrome Undergo Allogeneic Stem Cell Transplantation Prior to Progression to Acute Myelogenous Leukemia?
Authors: Schroeder Mark A. , Blum William 
Published: January 2011

Abstract
Case: A 65-year-old male who was previously in good health presented to his primary care physician with increasing fatigue over several months. He was found to be anemic (hemoglobin 7.5 mg/dL) and neutropenic (absolute neutrophil count 1000/μL). Further laboratory investigation showed an elevated erythropoietin level and normal iron stores. Bone marrow biopsy revealed dysplasia in two lineages and 8% blasts. Cytogenetic studies showed a clone with loss of 7q. He required red blood cell transfusions approximately every 2 weeks. He was started on hypomethylating agent treatment and referred for consultation regarding the role of hematopoietic stem cell transplantation. HLA typing results demonstrated that he had an HLA-identical sibling.
Allogeneic Hematopoietic Stem-Cell Transplantation for Myelodysplastic Syndrome
Authors: Cutler Corey 
Published: January 2011

Abstract
Transplantation is the only known cure for myelodysplastic syndrome (MDS). While some comparative analyses have demonstrated early transplantation to be the preferred strategy for all MDS patients, many of these analyses are biased. Using newly identified prognostic factors and models, a rational approach to transplantation can be undertaken. Factors such as transfusion dependency, cytogenetics, medical comorbidity, and World Health Organization (WHO) histologic subtype should all be considered when deciding on the role of transplantation for the MDS patient. Unresolved issues in transplantation include the impact of pre-transplant tumor debulking with traditional chemotherapeutic agents or the new DNA hypomethylating agents, and the optimal timing of reduced-intensity conditioning transplantation for older patients or for those with medical comorbidities.
Prognosis of Myelodysplastic Syndromes
Authors: Garcia-Manero Guillermo 
Published: January 2011

AbstractThe myelodysplastic syndromes (MDS) are a very complex group of hematopoietic disorders. The degree of complexity relates not only to the intrinsic pathobiological characteristics of the disease, but also to the group of patients whom it affects most frequently: older individuals or those who have been exposed to prior forms of chemotherapy. It is therefore crucial to develop clinical tools to predict with a certain degree of precision the prognosis and outcome for patients with specific subtypes of MDS in specific clinical situations. At the present time, patients with MDS are diagnosed using a set of well-established histopathological criteria. Prognosis is established using classifications that include morphological features, percentage of blasts, and clinical and molecular characteristics such as peripheral cytopenias and cytogenetics. The International Prognostic Scoring System (IPSS) is a classic example of this type of classification. Over the last 5 years, there has been an intense effort to develop new prognostic systems for MDS, and new molecular alterations with potential prognostic value have been discovered. Over the same period of time, several new therapeutic interventions have been developed for patients with MDS. Biomarkers of response to these agents, in particular for the hypomethylating agents, are needed to predict clinical benefit. This review summarizes current prognostic models of MDS and new molecular alterations with potential prognostic potential.
Clinical Use of Intravenous Iron: Administration, Efficacy, and Safety
Authors: Auerbach Michael , Ballard Harold 
Published: January 2011

AbstractThis section reviews the history, pharmacology, administration, efficacy, and toxicity of intravenous iron. Intravenous iron offers advantages over oral iron for the treatment of iron deficiency anemia across a wide range of disease states associated with absolute and functional iron deficiency. However, there remain concerns about the acute safety profiles of the available preparations and the potential for long-term toxicity with their repeated administration. Seven intravenous iron formulations are available. Confusion concerning the relative toxicities of the different formulations abounds. The similarities and differences are discussed. Iron repletion has been associated with adverse outcomes in infections. The relationship, if any, between intravenous iron administration and infections is reviewed. The potential advantages of total dose infusion (TDI), complete repletion in a single setting, are highlighted. A new paradigm for iron replacement therapy in iron deficiency anemia is presented.
Iron Deficiency and Heart Disease: Ironclad Evidence?
Authors: Carson Jeffrey L. , Adamson John W. 
Published: January 2011

Abstract
Patients with heart failure have elevated levels of circulating inflammatory cytokines and commonly have iron deficiency anemia or anemia of chronic inflammation. Clinical trials in patients with congestive heart failure and iron deficiency have demonstrated that intravenous iron treatment appears to improve subjective and objective outcomes. Most patients in these trials were not anemic or only had mild anemia, and hemoglobin concentration rose only slightly after treatment with iron. Experimental evidence demonstrates that iron is a cofactor for muscle function, which could explain the improvement in clinical outcomes. Many questions remain to be answered to understand the role of iron therapy in patients with congestive heart failure.
Parenteral Iron Therapy in Cancer-Associated Anemia
Authors: Henry David H. 
Published: January 2011

AbstractAnemia is common in cancer patients. Its cause is multifactorial, so a brief workup is always necessary to rule out simple, reversible causes. Anemia of chronic disease/inflammation and chemotherapy-induced anemia are the most common causes. Symptomatic or clinically severe anemia may require treatment with blood transfusion or an erythropoiesis-stimulating agent (ESA). If ESA therapy is chosen, developing evidence now suggests that, similar to chronic renal failure patients on hemodialysis, the addition of intravenous iron can improve the response to ESA because of iron-restricted erythropoiesis, even in the iron-replete patient.
Childhood Myelodysplastic Syndrome: Focus on the Approach to Diagnosis and Treatment of Juvenile Myelomonocytic Leukemia
Authors: Loh Mignon L. 
Published: January 2011

AbstractExpansion of myeloid blasts with suppression of normal hematopoiesis is a hallmark of acute myeloid leukemia (AML). In contrast, myeloproliferative neoplasms (MPNs) are clonal disorders characterized by overproliferation of one or more lineages that retain the ability to differentiate. Juvenile myelomonocytic leukemia (JMML) is an aggressive MPN of childhood that is clinically characterized by the overproduction of monocytic cells that can infiltrate organs, including the spleen, liver, gastrointestinal tract, and lung. Major progress in understanding the pathogenesis of JMML has been achieved by mapping out the genetic lesions that occur in patients. The spectrum of mutations described thus far in JMML occur in genes that encode proteins that signal through the Ras/mitogen-activated protein kinase (MAPK) pathways, thus providing potential new opportunities for both diagnosis and therapy. These genes include NF1, NRAS, KRAS, PTPN11, and, most recently, CBL. While the current standard of care for patients with JMML relies on allogeneic hematopoietic stem-cell transplant, relapse is the most frequent cause of treatment failure. Rarely, spontaneous resolution of this disorder can occur but is unpredictable. This review is focused on the genetic abnormalities that occur in JMML, with particular attention to germ-line predisposition syndromes associated with the disorder. Current approaches to therapy are also discussed.
Aplastic Anemia: First-line Treatment by Immunosuppression and Sibling Marrow Transplantation
Authors: Passweg Jakob R. , Marsh Judith C.W. 
Published: January 2011

Abstract
Newly diagnosed aplastic anemia is a serious condition, with more than 75% (higher in young patients) becoming long-term survivors if diagnosed and treated appropriately. First-line treatment approaches include immunosuppressive treatment using the combination of antithymocyte globulin and cyclosporine A for patients without a sibling donor and HLA identical sibling transplant for patients younger than age 40 with a donor. Best transplant strategies have been defined and include conditioning with cyclophosphamide and antithymocyte globulin, marrow as a stem cell source, and graft-versus-host diease prophylaxis using cyclosporine A and methotrexate. It is against these standard treatment approaches that any therapeutic progress has to be measured.
Pediatric Acute Lymphoblastic Leukemia: Is There Still a Role for Transplant?
Authors: Davies Stella M. , Mehta Parinda A. 
Published: January 2011

Abstract
Constant questioning of the applicability of transplant for any diagnosis is appropriate. This is particularly necessary in fields such as pediatric leukemia, in which significant progress in therapy and risk classification is being made. Outcomes with chemotherapy are constantly improving, and donor availability and transplant outcomes are also better. It is important to be aware of likely outcomes when counseling families and recommending therapy, and to consider issues of likely late side effects. Biological studies that predict prognosis, for example, array-based studies, hold hope of identifying the children destined to relapse at the outset of disease. However, a rigorous approach must be taken in determining whether transplant does improve outcome whenever this strategy is applied.
Treatment of Pediatric Chronic Myeloid Leukemia in the Year 2010: Use of Tyrosine Kinase Inhibitors and Stem-Cell Transplantation
Authors: Suttorp Meinolf , Millot Frédéric 
Published: January 2011

AbstractAllogeneic hematopoietic stem cell transplantation (allo-SCT) remains the only proven cure for chronic myeloid leukemia (CML), a rare malignancy in childhood. With the excellent results induced by the tyrosine kinase inhibitor (TKI) imatinib in adults in the last decade, the appropriate management of children with CML has also changed radically, and only a minority are now transplanted as a front-line treatment. Data on pediatric experiences with imatinib in CML from controlled trials remain very limited, but this review of available data describes the role of imatinib in children with CML, addressing: 1) the starting dose; 2) pharmacokinetics in childhood; 3) possible adverse effects, with a focus on the still-growing skeleton; 4) early monitoring of treatment efficacy in an attempt to avoid failure; 5) the timing of allo-SCT in children; and 6) treatment of CML relapse after allo-SCT. Because the characteristics of CML in children seem to overlap extensively with what is described in adult internal medicine, most answers and pediatric algorithms are adapted from the treatment of CML in adults. Today in 2010, allo-SCT in children should be postponed until CML becomes refractory to imatinib. The approach for young patients with suboptimal responses is unclear because data on the efficacy and safety of second-generation TKIs in childhood are almost entirely missing. Other than being included in a formal trial on second-generation TKIs, allo-SCT for patients failing imatinib remains the first choice.
Evidence-Based Mini-Review: Is Indium-Labeled Autologous Platelet Scanning Predictive of Response to Splenectomy in Patients With Chronic Immune Thrombocytopenia?
Authors: Cuker Adam , Cines Douglas B. 
Published: January 2011

Abstract
Clinical scenario: An otherwise healthy 25-year-old woman returns to your office for management of chronic primary immune thrombocytopenia. She was diagnosed 6 months earlier and continues to require prednisone 15 mg daily and periodic infusions of intravenous immunoglobulin to maintain a hemostatic platelet count. You discuss second-line treatment options, including splenectomy. The patient asks if there are any means by which to predict likelihood of response to splenectomy. You have heard about the use of indium-labeled autologous platelet scanning for this purpose and wonder what the evidence shows.
Understanding and Evaluating Platelet Function
Authors: Brass Lawrence 
Published: January 2011

AbstractThe contribution of platelets to normal hemostasis and vascular disease is well described. However, recent studies make it clear that much remains to be learned about platelet activation at the single cell and the molecular level, and about the contribution of platelets to inflammation, tumor angiogenesis, and embryonic development. This article is divided into two themes. The first is an overview of current knowledge of the mechanisms that drive platelet function in vivo and a brief summary of some of the emerging ideas that are modifying older views. The second theme is a consideration of the strengths and weaknesses of the tools we have as hematologists to assess platelet function in the clinical setting, identify mechanisms, and evaluate the impact of antiplatelet agents.
Thrombocytopenia in Pregnancy
Authors: McCrae Keith R. 
Published: January 2011

AbstractThrombocytopenia occurs commonly during pregnancy, and may result from diverse etiologies. Awareness of these many causes facilitates proper diagnosis and management of thrombocytopenia in the pregnant setting. Some causes of thrombocytopenia are unique to pregnancy and may not be familiar to hematologists. In the review, we will discuss the differential diagnosis of thrombocytopenia in pregnancy, and the pathogenesis of selected thrombocytopenic disorders. Considerations for optimal management of the pregnant patient with thrombocytopenia will also be described.
Neurobiological Mechanisms of Pain in Sickle Cell Disease
Authors: Wang Zaijie J. , Wilkie Diana J. , Molokie Robert 
Published: January 2011

AbstractPain is a frequent complaint of people living with sickle cell disease (SCD); however, the neurobiology of pain in SCD remains poorly understood. Whereas this pain has been thought to be primarily related to visceral and somatic tissue injury subsequent to vaso-occlusion events, emerging evidence from human and animal studies has suggested that a component of SCD pain may be related to neuropathic processes. Significant knowledge has been obtained from studies of molecular and neurobiological mechanisms leading to and maintaining neuropathic pain. Some of the most promising evidence has implicated major roles of protein kinase C and Ca2+/calmodulin-dependent protein kinase II, and their interaction with the N-methyl-D-aspartate receptors and the transient receptor potential vanilloid 1 receptor in the development of neuropathic pain. The latest evidence from our studies suggests that these pathways are important for SCD pain as well. Coupled with emerging animal models of SCD pain, we can now start to elucidate neurobiological mechanisms underlying pain in SCD, which may lead to better understanding and effective therapies.
Sickle-Cell Pain: Advances in Epidemiology and Etiology
Authors: Smith Wally R. , Scherer Marshall 
Published: January 2011

AbstractNew epidemiological findings recast pain in sickle-cell disease (SCD) as being more often a chronic manifestation than was previously thought, although acute pain is still the hallmark of the disease. SCD pain intensity, the number of painful locations, and the frequency of hospitalizations due to SCD pain may worsen with age. In adults and even in children, the quantity and severity of SCD pain may be vastly underestimated, because most of the “iceberg” of SCD pain is “submerged” at home, and only the tip of the iceberg is seen by health care providers when acute SCD care is rendered in emergency rooms and hospitals. Implications of this “iceberg phenomenon” are significant for clinicians, researchers, employers, policy makers, and the public. Nevertheless, both emergency room and hospital utilization for SCD pain remain prevalent. Often, utilization recurs early, perhaps emblematic of poor acute pain management. New data show the protean impacts of SCD pain on health-related quality of life, sleep, and psychological and social health. The relationship of the severity of SCD pain to the severity of underlying sickle vasculopathy is unclear, but epidemiologic evidence and patient descriptors suggest a temporal evolution of pain mechanisms. At first, increasingly worse nociceptive pain from vaso-occlusion and local lesions may evolve over the first two decades of life. Then, in the third and following decades, central neuropathic pain may also evolve due to past and continuing nociceptive stimuli. New findings confirm environmental contributors to SCD pain, including seasonal (colder) temperatures, barometric pressure, and wind speed.
Evidence-Based Mini-Review: Are Systemic Corticosteroids an Effective Treatment for Acute Pain in Sickle Cell Disease?
Authors: Black L. Vandy , Smith Wally R. 
Published: January 2011

Abstract
An 18-year-old African-American male with sickle cell disease (SCD) is admitted to the hospital with a vaso-occlusive pain crisis affecting his chest and right upper extremity. He has a history of asthma but does not have a fever or respiratory symptoms, and a chest X-ray is negative for an infiltrate. He is treated with intravenous fluids and morphine. You are asked about the potential efficacy of systemic corticosteroids as an adjunctive treatment for pain control.