bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alemtuzumab Use In Relapsed and Refractory Chronic Lymphocytic Leukemia
Authors: Arnason Jon E. , Brown Jennifer R. 
Published: December 2011

Abstract
A 62-year-old woman with chronic lymphocytic leukemia (CLL) who initially presented with lymphocytosis and 13q deletion in 1996 now presents to the clinic for recommendations regarding relapsed disease. The patient has received multiple prior therapies, including single-agent fludarabine, fludarabine and rituximab, and bendamustine and rituximab. She now has recurrent lymphocytosis with a WBC count that has increased from 13 000 2 months ago to 115 000 today and a platelet count of 55 000 but no lymphadenopathy. In addition, your evaluation finds that she has acquired a 17p deletion.
Endovascular Procedures in the Management of DVT
Authors: Vedantham Suresh 
Published: December 2011

Abstract
The post-thrombotic syndrome (PTS) develops in 25%-50% of patients with proximal lower extremity deep vein thrombosis (DVT) despite the use of standard anticoagulant therapy and elastic compression stockings. PTS is a major cause of quality of life impairment in DVT patients and often leads to limiting venous claudication, work disability, and venous ulcers. Endovascular thrombolytic procedures that eliminate venous thrombus, restore venous flow, and show strong potential to prevent PTS are now under study in multicenter randomized clinical trials. In addition, endovascular procedures can be used to treat valvular reflux and venous obstruction and thereby provide symptom improvement to patients with chronic established PTS.
New Insights into Therapeutic Targets in Myeloma
Authors: Anderson Kenneth C. 
Published: December 2011

Abstract
Patient outcome in multiple myeloma (MM) has been remarkably improved due to the use of combination therapies including proteasome inhibitors and immunomodulatory drugs, which target the tumor in its BM microenvironment. Ongoing efforts to improve the treatment paradigm even further include using oncogenomics to better characterize molecular pathogenesis and to develop refined patient stratification and personalized medicine in MM; using models of MM in its BM milieu to identify novel targets and to validate next-generation therapeutics directed at these targets; developing immune-based therapies including mAbs, immunotoxins targeting MM cells and cytokines, and novel vaccine strategies; and using functional oncogenomics to inform the design of novel combination therapies. With continued rapid evolution of progress in these areas, MM will be a chronic illness with sustained complete response in a significant number of patients.
Posttransplantation Maintenance Therapy and Optimal Frontline Therapy in Myeloma
Authors: Reece Donna E. 
Published: December 2011

Abstract
One of the major efforts to improve the results of intensive therapy and autologous stem cell transplantation (ASCT) in multiple myeloma involves the integration of novel agents into the transplantation sequence. This can include their administration before, during, and after the transplantation procedure. Several phase 2 and 3 studies have evaluated the use of novel agents as part of induction therapy before transplantation to produce higher response rates and progression-free survival (PFS). Similarly, posttransplantation maintenance—or consolidation—with these agents consistently improves PFS. Survival benefits have been more difficult to demonstrate, although one trial using bortezomib before and after transplantation and a second using lenalidomide as maintenance have shown significantly longer survival times. This article reviews the different regimens used with ASCT, with an emphasis on randomized trials.
What is the Benefit of Maintenance Therapy with Lenalidomide or Bortezomib after Autologous Stem Cell Transplantation in Multiple Myeloma and What is the Risk of Developing a Secondary Primary Malignancy?
Authors: Scott Emma , Reece Donna 
Published: December 2011

Abstract
An otherwise healthy 60-year-old male was diagnosed with stage II multiple myeloma by the International Staging System characterized by anemia, diffuse lytic bone lesions, IgG kappa paraproteinemia, 45% bone marrow plasmacytosis and the t(4;14) by FISH and conventional cytogenetics. The patient had a very good partial remission with initial induction therapy consisting of four 3-week cycles of bortezomib 1.3 mg/m2 IV on days 1, 4, 8, and 11 plus dexamethasone 40 mg days 1-4 (all cycles), followed by a cyclophosphamide and G-CSF mobilized melphalan 200 mg/m2 autologous stem cell transplantation (ASCT) and experienced minimal side effects. He is doing well 60 days post-ASCT and is in a near complete remission. His oncologist recommends maintenance therapy with lenalidomide or bortezomib, but the patient is concerned about the increased risk of developing a secondary malignancy (SM), and because he has had such an encouraging response to induction therapy, he wonders if he could remain off therapy.
Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy
Authors: Parker Charles J. 
Published: December 2011

AbstractDespite the availability of safe, effective targeted therapy that controls intravascular hemolysis, the management of paroxysmal nocturnal hemoglobinuria (PNH) remains complicated because of disease heterogeneity and close association with BM failure syndromes. The purpose of this review is to provide a framework for individualizing treatment based on disease classification. According to the recommendations of the International PNH Interest Group, patients can be placed into one of the following 3 categories: (1) classic PNH, (2) PNH in the setting of another BM failure syndrome, or (3) subclinical PNH. The PNH clone in patients with subclinical disease is insufficiently large to produce even biochemical evidence of hemolysis, and consequently, patients who fit into this category require no PNH-specific therapy. Patients with PNH in the setting of another BM failure syndrome (usually aplastic anemia or low-risk myelodysplastic syndrome) have at least biochemical evidence of hemolysis, but typically the PNH clone is small (< 10%) so that hemolysis does not contribute significantly to the underlying anemia. In these cases, the focus of treatment is on the BM failure component of the disease. Intravascular hemolysis is the dominant feature of classic PNH, and this process is blocked by the complement inhibitor eculizumab. The thrombophilia of PNH also appears to be ameliorated by eculizumab, but the drug has no effect on the BM failure component of the disease. Low-grade extravascular hemolysis due to complement C3 opsonization develops in most patients treated with eculizumab, and in some cases is a cause for suboptimal response to treatment. Allogeneic BM transplantation can cure classic PNH, but treatment-related toxicity suggests caution for this approach to management.
Novel Antibody-Based Therapies For Acute Lymphoblastic Leukemia
Authors: Hoelzer Dieter 
Published: December 2011

AbstractA major breakthrough in the treatment of acute lymphoblastic leukemia (ALL) was the availability of targeted therapies targeting either specific transcripts, such as bcr-abl fusion protein by tyrosine kinase inhibitors (TKIs), or specific antigens by mAbs. ALL blast cells express a variety of specific antigens (eg, CD19, CD20, CD22, CD33, and CD52) that serve as targets for mAbs. To date, the most data are available for anti-CD20 (rituximab), which has been combined with chemotherapy for the treatment of mature B-ALL/Burkitt lymphoma. Studies with rituximab have also been completed in B-precursor ALL. Another antigen, CD19, is of great interest due to a very high rate of expression in ALL. It can be targeted by a bispecific mAb, blinatumomab, directed against CD19 and CD3. Smaller studies or case reports are also available for the anti-CD52 (alemtuzumab), anti-CD22 (epratuzumab), and anti-CD33 (gemtuzumab) mAbs. Available data demonstrate that mAb therapy in ALL is a highly promising treatment approach. However, several details for an optimal treatment approach, such as the required level of antigen expression, timing, schedule, dosage, and stage of disease, still need to be defined.
Successes and Failures of Stem Cell Transplantation in Autoimmune Diseases
Authors: Tyndall Alan 
Published: December 2011

Abstract
Over the past 15 years, more than 1500 patients have received HSCT, mostly autologous, as treatment for a severe autoimmune disease (AD). More than 1000 of these have been registered in the European Group for Bone Marrow Transplantation (EBMT) and European League Against Rheumatism (EULAR) combined database. A recent retrospective analysis of 900 patients showed that the majority had multiple sclerosis (MS; n = 345) followed by systemic sclerosis (SSc; n = 175), systemic lupus erythematosus (SLE; n = 85), rheumatoid arthritis (RA; n = 89), juvenile idiopathic arthritis (JIA; n = 65), and idiopathic cytopenic purpura (ITP; n = 37). An overall 85% 5-year survival and 43% progression-free survival was seen, with 100-day transplantation-related mortality (TRM) ranging between 1% (RA) and 11% (SLE and JIA). Approximately 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many patients, such as in those with SSc, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented beyond any predicted known effects of intense immunosuppression alone. The high TRM was in part related to conditioning intensity, comorbidity, and age, but until the results of the 3 prospective randomized trials are known, an evidence-based modification of the conditioning regimen will not be possible.1 In recent years, multipotent mesenchymal stromal cells (MSCs) have been tested in various AD, exploiting their immune-modulating properties and apparent low acute toxicity. Despite encouraging small phase 1/2 studies, no positive data from randomized, prospective studies are as yet available in the peer-reviewed literature.
Allogeneic Immunotherapy to Optimize the Graft-versus-Tumor Effect: Concepts and Controversies
Authors: Porter David L. 
Published: December 2011

AbstractAllogeneic stem cell transplantation (SCT) can be considered the most successful method of adoptive immunotherapy of cancer. It is successful in part because of the potent graft-versus-tumor (GVT) effects of the donor graft, which are independent of the conditioning regimen. This potent GVT reaction can be harnessed in some cases to treat patients who relapse after allogeneic SCT with the use of donor leukocyte infusions (DLIs). This has led to the rapid development of reduced-intensity conditioning (RIC) regimens for allogeneic SCT, an approach that relies primarily on GVT activity. However, the effects of GVT have clear disease specificity and remain associated with significant GVHD. Optimization of GVT induction will require a better understanding of the important target antigens and effector cells, as well as the development of methods that enhance GVT reactivity without excessive GVHD. The appropriate clinical setting and timing for GVT induction need to be defined more clearly, but ultimately, the immunologic control of cancer through allogeneic adoptive immunotherapy represents one of the most potent and promising therapeutic strategies for patients with hematologic malignancies.
Positron Emission Tomography in the Management of Hodgkin Lymphoma
Authors: Connors Joseph M. 
Published: December 2011

Abstract
Accurate imaging of lymphoma is essential for optimal management. Positron emission tomography (PET), by providing both anatomic and functional information, is fundamentally altering staging, monitoring of response, response assessment, and choice of treatment modality for lymphomas, including Hodgkin lymphoma. This imaging technique, when used carefully in conjunction with standard testing, increases the sensitivity of lesion detection, provides an opportunity to monitor the quality of response during treatment, permits separation of fibronecrotic scar tissue from viable tumor, and adds prognostic information. PET has become integral to modern lymphoma management, but as a relatively new diagnostic technique, it is still being studied and neither its full potential nor its major limitations are fully understood. Discussed herein are recent observations from clinical trials and single-center experiences with PET to explore its advantages and limitations from a clinician's point of view.
Tricky and Terrible T-Cell Tumors: These are Thrilling Times for Testing: Molecular Pathology of Peripheral T-Cell Lymphomas
Authors: de Leval Laurence , Gaulard Philippe 
Published: December 2011

Abstract
Peripheral T-cell lymphomas (PTCLs) encompass a group of rare and usually clinically aggressive diseases. The classification and diagnosis of these diseases are compounded by their marked pathological heterogeneity and complex clinical features. With the exception of ALK-positive anaplastic large cell lymphoma (ALCL), which is defined on the basis of ALK rearrangements, genetic features play little role in the definition of other disease entities. In recent years, hitherto unrecognized chromosomal translocations have been reported in small subsets of PTCLs, and genome-wide array-based profiling investigations have provided novel insights into their molecular characteristics. This article summarizes the current knowledge on the best-characterized genetic and molecular alterations underlying the pathogenesis of PTCLs, with a focus on recent discoveries, their relevance to disease classification, and their management implications from a diagnostical and therapeutical perspective.
Targeting Epigenetic Programs in MLL-Rearranged Leukemias
Authors: Bernt Kathrin M. , Armstrong Scott A. 
Published: December 2011

Abstract
Rearrangements of the Mixed-Lineage Leukemia (MLL) gene are found in > 70% of infant leukemia, ∼ 10% of adult acute myelogenous leukemia (AML), and many cases of secondary acute leukemias. The presence of an MLL rearrangement generally confers a poor prognosis. There are more than 60 known fusion partners of MLL having some correlation with disease phenotype and prognosis. The most common fusion proteins induce the inappropriate expression of homeotic (Hox) genes, which, during normal hematopoiesis, are maintained by wild-type MLL. MLL-rearranged leukemias display remarkable genomic stability, with very few gains or losses of chromosomal regions. This may be explained by recent studies suggesting that MLL-rearranged leukemias are largely driven by epigenetic dysregulation. Several epigenetic regulators that modify DNA or histones have been implicated in MLL-fusion driven leukemogenesis, including DNA methylation, histone acetylation, and histone methylation. The histone methyltransferase DOT1L has emerged as an important mediator of MLL-fusion–mediated leukemic transformation. The clinical development of targeted inhibitors of these epigenetic regulators may therefore hold promise for the treatment of MLL-rearranged leukemia.
Recommendations for Broader Coverage Antifungal Prophylaxis in Childhood Acute Myeloid Leukemia: ASH Evidence-Based Review 2011
Authors: Gramatges Maria M. , Winter Stuart S. 
Published: December 2011

AbstractA 16-year-old female diagnosed with acute myeloid leukemia (AML) with inversion 16, a favorable prognostic indicator, has persistent neutropenia after her fourth cycle of dose-intensified chemotherapy. She was recently admitted for treatment with empiric antibiotics for febrile neutropenia, and an astute intern noticed a new lesion on her right foot with a dark necrotic center. A biopsy of the lesion showed spreading hyphae, consistent with Aspergillus. Despite her compliance with fluconazole fungal prophylaxis, computed tomography imaging revealed disseminated aspergillosis involving her lungs, liver, and kidneys. Amphotericin was started, but systemic fungemia and the development of multiorgan failure resulted in her death. You are in the difficult position of having to explain to her parents that she died in remission from chemotherapy-related complications. All of those involved in this unfortunate scenario wonder if something could have been done to prevent her death.
Diagnosis and Management of Immune Thrombocytopenia in the Era of Thrombopoietin Mimetics
Authors: Liebman Howard A. , Pullarkat Vinod 
Published: December 2011

Abstract
The recognition of that patients with Immune Thrombocytopenia (ITP) have functional thrombopoietin deficiency and decreased platelet production due to immune-mediated megakaryocytic injury has challenged the traditional view of this disease as predominantly a disorder of antibody-mediated platelet destruction. The therapy of chronic refractory ITP has been transformed by the approval of the thrombopoietin minetics, romiplostim and eltrombopag, which have shown remarkable efficacy in randomized trials. The use of these agents earlier in the disease course after failure of corticosteroid therapy remains controversial. In this article, we review the current data on the efficacy and safety of thrombopoietin receptor agonists and discuss other therapies as well as diagnostic work up of ITP.
Acquired Disorders of Platelet Function
Authors: Konkle Barbara A. 
Published: December 2011

AbstractPlatelet dysfunction is commonly acquired due to medications, procedures, medical conditions, and underlying hematologic disease. These issues are presented, the data reviewed, and recommendations given herein. Many medications and dietary supplements have platelet-inhibitory effects in vitro, although the clinical effects on bleeding risks are unclear for many. Platelet-inhibitory drugs are key in the treatment of vascular disease. Data are available to aid in the management of these medications to prevent hemorrhagic complications. Bleeding in patients with renal failure has decreased with improved dialysis and the use of erythropoietin, but remains a challenge. Platelet dysfunction accompanies cardiac valvular disease and use of cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation. Hematologic disorders including myeloproliferative disorders (MPDs), myelodysplasia, paraproteinemias, and immune thrombocytopenia (ITP) can also be associated with hemorrhagic complications due to platelet dysfunction. Knowledge of which factors affect bleeding risk and how to treat individuals with acquired platelet dysfunction are important in optimizing patient care.
What Is the Evidence for Using Hydroxyurea for Secondary Stroke Prevention?
Authors: Lebensburger Jeffrey D. , DeBaun Michael R. , Thompson Alexis A. 
Published: December 2011

Abstract
A 10-year-old male patient with hemoglobin SS suffered a stroke at 7 years of age and was initially transfused at the time of presentation to lower the hemoglobin S concentration to < 30%. You are asked by the family if their child can be treated with oral hydroxyurea rather than monthly transfusions for the secondary prevention of strokes.
Immunoregulatory Effects of Stored Red Blood Cells
Authors: Yazdanbakhsh Karina , Bao Weili , Zhong Hui 
Published: December 2011

AbstractSome clinical studies have identified potential adverse patient outcomes associated with RBC storage length. This may in part be due to the release of potentially hazardous bioactive products that accumulate during storage and are delivered at high concentrations during transfusion. In this situation, a proinflammatory tissue microenvironment may be established that can alter immunoregulatory mechanisms. This review highlights some of the potential immunomodulatory effects of stored RBCs that may be responsible for adverse transfusion reactions.
Genetics of Myelodysplastic Syndromes: New Insights
Authors: Graubert Timothy , Walter Matthew J. 
Published: December 2011

Abstract
Myelodysplastic syndromes (MDS) are a heterogenous group of hematologic malignancies characterized by clonal expansion of BM myeloid cells with impaired differentiation. The identification of recurrent mutations in MDS samples has led to new insights into the pathophysiology of these disorders. Of particular interest is the recent recognition that genes involved in the regulation of histone function (EZH2, ASXL1, and UTX) and DNA methylation (DNMT3A, IDH1/IDH2, and TET2) are recurrently mutated in MDS, providing an important link between genetic and epigenetic alterations in this disease. The mechanism by which these mutated genes contribute to disease pathogenesis is an active area of research, with a current focus on which downstream target genes may be affected. Recent advances from sequencing studies suggest that multiple mutations are required for MDS initiation and progression to acute myeloid leukemia (AML). The past several years have yielded many new insights, but the complete genetic landscape of MDS is not yet known. Moreover, few (if any) of the findings are sufficiently robust to be incorporated into routine clinical practice at this time. Additional studies will be required to understand the prognostic implications of these mutations for treatment response, progression to AML, and survival.
Advances in Antiplatelet Therapy
Authors: Michelson Alan D. 
Published: December 2011

Abstract
Because of the central role of platelets in cardiovascular atherothrombosis, there is a well-established therapeutic role for antiplatelet therapy that includes aspirin (a cyclooxygenase 1 [COX1] inhibitor), clopidogrel (an antagonist of the ADP P2Y12 receptor), and the GPIIb-GPIIIa (αIIbβ3) antagonists. However, there remains a significant incidence of arterial thrombosis in patients treated with currently available antiplatelet therapy. Novel P2Y12 antagonists such as the recently US Food and Drug Administration (FDA)–approved prasugrel, along with ticagrelor, cangrelor, and elinogrel, have advantages over clopidogrel, including more rapid, less variable, and more complete inhibition of platelet function. Currently ongoing phase 3 studies will determine whether these new P2Y12 antagonists will result in better and/or more rapid antithrombotic effects than clopidogrel, without an unacceptable increase in hemorrhagic or other side effects, as has been recently reported in some clinical settings for prasugrel and ticagrelor. Antagonists of the thrombin receptor protease-activated receptor 1 (PAR1) are also undergoing phase 3 trials, and many other novel antiplatelet agents are under investigation as antithrombotic agents.
Too Much of a Good Thing at the Site of Tissue Injury: The Instructive Example of the Complement System Predisposing to Thrombotic Microangiopathy
Authors: Liszewski M. Kathryn , Atkinson John P. 
Published: December 2011

Abstract
The interplay between the complement and coagulation systems is just beginning to be explored and characterized. This interaction, however, is ancient. For example, if endotoxin is added to the hemolymph of the horseshoe crab, a protease is activated that triggers both the coagulation and complement systems. However, in extant mammals, these 2 cascades have diverged. These infamous “terrible C's” are the scourge of many a medical student (and possibly even a few hematologists). They also are intimately involved in the pathophysiology of thrombomicroangiopathies (TMAs). The complement system generates a procoagulant microenvironment and the coagulation system forms a clot in the renal microvasculature, and thus the 2 systems are partners in mediating multiple pathophysiological conditions.