bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line therapy for young patients with CLL
Authors: Jain Nitin , O’Brien Susan 
Published: December 2016

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 fellow you are supervising about the best treatment of this patient.
Chronic myeloid leukemia: sequencing of TKI therapies
Authors: Cortes Jorge , Kantarjian Hagop 
Published: December 2016

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). Sequencing of TKIs has become standard practice, and the proper use of sequenced TKIs is likely to optimize outcomes and resource utilization.
Thrombosis in the setting of cancer
Authors: Streiff Michael B. 
Published: December 2016

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 patients are receiving cancer treatment. The efficacy of direct oral anticoagulants in the treatment of cancer-associated thrombosis remains incompletely defined. Central venous catheter (CVC)–associated VTE should be treated with anticoagulation alone, unless the CVC is no longer required. Recent studies indicate that anticoagulation may be appropriate for patients with persistent thrombocytopenia or solid tumor brain metastases. Management of recurrent VTE includes the identification of the cause(s) of the recurrence and solutions targeted at addressing the potential precipitants.
Anti-Xa monitoring of low-molecular-weight heparin in adult patients with cancer
Authors: Kreuziger Lisa Baumann , Streiff Michael 
Published: December 2016

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?
Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria
Authors: Parker Charles J. 
Published: December 2016

AbstractOnce 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, relationship between PNH and immune-mediated bone marrow failure, and that PNH is an acquired, nonmalignant clonal disease of the hematopoietic stem cells. Bone marrow failure complicates management of PNH because compromised erythropoiesis contributes, to a greater or lesser degree, to the anemia; in addition, the extent to which the mutant stem cell clone expands in an individual patient determines the magnitude of the hemolytic component of the disease. An understanding of the unique pathobiology of PNH in relationship both to complement physiology and immune-mediated bone marrow failure provides the basis for a systematic approach to management.
Cold agglutinin disease
Authors: Berentsen Sigbjørn 
Published: December 2016

AbstractPrimary 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. CAD should not be treated with corticosteroids. Based on an individualized approach, rituximab monotherapy or rituximab-fludarabine in combination is recommended as first-line therapy. Rituximab-bendamustine is still an investigational therapy. Although complement-modulating agents are still to be considered experimental in CAD, therapy with the anti-C1s monoclonal antibody TNT009 seems promising.
Congenital and acquired bleeding disorders in pregnancy
Authors: Gernsheimer Terry B. 
Published: December 2016

AbstractObstetrical 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 includes the hematologist, obstetrician, and anesthesiologist; the patient should be followed closely during pregnancy, through delivery, and in the immediate postpartum period. Acquired disorders of hemostasis that occur with pregnancy may present particular diagnostic difficulties and require rapid diagnosis and management.
Platelets in infectious disease
Authors: Middleton Elizabeth , Rondina Matthew T. 
Published: December 2016

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 sepsis is needed. Platelets are small, anucleate cells that have hemostatic, inflammatory, and immune-mediating properties. Platelets are the second most common circulating blood cell, and emerging evidence suggests that platelets serve as sentinel and effector cells during infectious syndromes. Nevertheless, the molecular and functional changes that occur in platelets during sepsis, and their impact on the clinical course of infected patients, remain incompletely understood. In this review, we first highlight the complex and dynamic pathophysiology characteristics of acute, systemic infections and we then discuss established and emerging evidence of the roles of platelets in sepsis.
Frontline strategy for follicular lymphoma: are we ready to abandon chemotherapy?
Authors: Fowler Nathan 
Published: December 2016

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 chemotherapy. However, these regimens are also associated with significant cost as well as a unique toxicity profile. Large randomized studies are underway to compare noncytotoxic regimens with chemotherapy in the frontline, and several new combinations are being tested in the phase 2 setting. Ongoing work to identify predictive biomarkers and investment in mechanistic studies will ultimately lead to the personalization of therapy in the frontline setting for follicular lymphoma.
Diffuse large B-cell lymphoma: R-CHOP failure—what to do?
Authors: Coiffier Bertrand , Sarkozy Clémentine 
Published: December 2016

AbstractAlthough 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 refractory patients exhibit double-hit lymphoma (MYC-BCL2 rearrangement) or double-protein-expression lymphoma (MYC-BCL2 hyperexpression) which have a more aggressive clinical picture. New strategies are currently being explored to obtain better CR rates and fewer relapses. Although young relapsing patients are treated with high-dose therapy followed by autologous transplant, there is an unmet need for better salvage regimens in this setting. To prevent relapse, maintenance therapy with immunomodulatory agents such as lenalidomide is currently undergoing investigation. New drugs will most likely be introduced over the next few years and will probably be different for relapsing and refractory patients.
Checkpoint inhibition and cellular immunotherapy in lymphoma
Authors: Lulla Premal , Heslop Helen E. 
Published: December 2016

AbstractHodgkin and non-Hodgkin lymphoma are both good targets for immunotherapy, as they are accessible to antibodies and cell-based immunotherapy, express costimulatory molecules, and express lineage-restricted, viral, and unique tumor antigens. Blockade of the programmed-death 1 (PD-1) immune checkpoint has produced very encouraging response rates in patients with Hodgkin lymphoma, whereas adoptive transfer of Epstein-Barr Virus (EBV)-specific T cells has shown clinical activity in patients with posttransplant lymphoma and other EBV-associated lymphomas. T cells can also be genetically modified with chimeric antigen receptors (CARs) to confer specificity for surface antigens, and studies of CD19 CARs in lymphoma also have had encouraging response rates. Future directions include combination of checkpoint blockade and adoptive T-cell studies.
The post-thrombotic syndrome
Authors: Kahn Susan R. 
Published: December 2016

Abstract
The post-thrombotic syndrome (PTS) is a frequent, sometimes disabling complication of deep vein thrombosis (DVT) that reduces quality of life and is costly. This article discusses risk factors for PTS after DVT and available means to prevent and treat PTS, with a focus on new information in the field. After DVT, PTS will develop in 20% to 50% of patients, and severe PTS, including venous ulcers, will develop in 5% to 10%. The principal risk factors for PTS are anatomically extensive DVT, recurrent ipsilateral DVT, persistent leg symptoms 1 month after acute DVT, obesity, and older age. By preventing the initial DVT and ipsilateral DVT recurrence, primary and secondary prophylaxes of DVT will prevent cases of PTS. Based on recent evidence from a large multicenter trial, routine use of elastic compression stockings (ECS) after DVT to prevent PTS is not advocated, but in patients with DVT-related leg swelling that is bothersome, a trial of ECS is reasonable. Selecting DVT patients for catheter-directed thrombolytic treatment as a means of preventing PTS should be done on a case-by-case basis, with a focus on patients with extensive thrombosis, recent symptoms onset, and low bleeding risk. For patients with established PTS, daily use of ECS may help to relieve symptoms and edema. Intermittent compression devices can be tried in patients with moderate-to-severe PTS whose symptoms are inadequately controlled with ECS alone. A supervised exercise training program may improve PTS symptoms. Management of post-thrombotic ulcers should ideally involve a multidisciplinary approach. Important areas for future research are summarized.
Understanding red blood cell alloimmunization triggers
Authors: Hendrickson Jeanne E. , Tormey Christopher A. 
Published: December 2016

AbstractBlood group alloimmunization is “triggered” when a person lacking a particular antigen is exposed to this antigen during transfusion or pregnancy. Although exposure to an antigen is necessary for alloimmunization to occur, it is not alone sufficient. Blood group antigens are diverse in structure, function, and immunogenicity. In addition to red blood cells (RBCs), a recipient of an RBC transfusion is exposed to donor plasma, white blood cells, and platelets; the potential contribution of these elements to RBC alloimmunization remains unclear. Much attention in recent years has been placed on recipient factors that influence RBC alloantibody responses. Danger signals, identified in murine and human studies alike as being risk factors for alloimmunization, may be quite diverse in nature. In addition to exogenous or condition-associated inflammation, autoimmunity is also a risk factor for alloantibody formation. Triggers for alloimmunization in pregnancy are not well-understood beyond the presence of a fetal/maternal bleed. Studies using animal models of pregnancy-induced RBC alloimmunization may provide insight in this regard. A better understanding of alloimmunization triggers and signatures of “responders” and “nonresponders” is needed for prevention strategies to be optimized. A common goal of such strategies is increased transfusion safety and improved pregnancy outcomes.
Treatment options for patients with myelodysplastic syndromes after hypomethylating agent failure
Authors: Carraway Hetty E. 
Published: December 2016

Abstract
The treatment of patients with myelodysplastic syndromes (MDSs) has hinged primarily on supportive care (ie, blood transfusions, colony stimulating agents, iron chelation, etc.) and the US Food and Drug Administration-approved agents, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For patients no longer benefitting from these agents, there is a paucity of effective therapies. The challenges at this time include our limited understanding of the mechanisms of resistance to these therapies and the variables employed to select next best therapies for patients based on: (1) their performance status and medical comorbidities; (2) the molecular feature(s) of their MDS; (3) the prior treatments they have received; and (4) the long-term goal(s)/possibilities for their future treatment (ie, transplant vs no transplant).
Transplantation for myelodysplastic syndromes: who, when, and which conditioning regimens
Authors: Saber Wael , Horowitz Mary M. 
Published: December 2016

Abstract
Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for myelodysplastic syndrome (MDS). Broad application is hindered by high risks of transplant-related morbidity and mortality, especially in the older age range represented by the MDS population. However, recent advances in strategies to minimize regimen-related toxicity make HCT a viable option for many more patients. Appropriate selection of patients involves consideration of patient factors, including use of geriatric assessment tools and comorbidity scales, that predict risks of regimen-related toxicity as well as disease factors, including genetic markers, which predict survival with both non-HCT and HCT therapy. Optimal timing of HCT for fit patients must consider MDS risk scores and life-years to be gained, with earlier transplantation indicated for patients with intermediate-2 and high-risk disease but judicious delay for lower risk patients. Selection of suitable conditioning regimens must balance risks of toxicity with opportunity for maximum disease control.
Sequencing of nontransplant treatments in multiple myeloma patients with active disease
Authors: Yee Andrew J. , Raje Noopur S. 
Published: December 2016

AbstractThe approval of several different classes of drugs in recent years has resulted in a dramatic expansion of treatment options for multiple myeloma patients, improving both survival and quality of life. Lenalidomide and bortezomib are now core components of treatment both at time of diagnosis and at relapse. Next-generation immunomodulatory drugs, like pomalidomide, and newer proteasome inhibitors like carfilzomib and ixazomib are available for use at relapse. Drugs with novel mechanisms of action such as the histone deacetylase inhibitor panobinostat and the monoclonal antibodies targeting SLAMF7 (elotuzumab) and CD38 (daratumumab) are significant steps forward. Recent clinical trials describing novel combinations of these drugs have demonstrated unprecedented improvements in efficacy while maintaining tolerability. All of these options provide not only a challenge for choice of therapy, but also the opportunity to aim for increasing depth of response. This chapter will describe an approach on how to sequence and incorporate these therapies, focusing on patients where high-dose melphalan and autologous stem cell transplant are deferred or not applicable.
Advances and practical use of monoclonal antibodies in multiple myeloma therapy
Authors: Lee Hans C. , Weber Donna M. 
Published: December 2016

Abstract
The use of proteasome inhibitors and immunomodulatory agents in the treatment of myeloma have resulted in significant improvements in patient outcomes over the last decade. Although these agents now form the backbone of current myeloma treatment regimens both in the frontline and in a relapsed setting, drug resistance remains an inevitable challenge that most patients will encounter during their disease course. Hence, new treatment strategies continue to be explored, and the recent regulatory approvals of the monoclonal antibodies (mAbs) daratumumab (DARA) and elotuzumab (ELO), which target the plasma cell surface proteins CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), respectively, have heralded the long-awaited era of antibody-based approaches in the treatment of myeloma. Hoping to build on these advances, a number of other mAbs are in various stages of clinical development, including those targeting myeloma cell surface antigens, the bone marrow microenvironment, and immune effector T cells such as anti-programmed cell death protein 1 antibodies. In this review, the current landscape and practical use of mAb-based therapy in myeloma will be discussed.
Single-dose intravenous iron for iron deficiency: a new paradigm
Authors: Auerbach Michael , Deloughery Thomas 
Published: December 2016

AbstractIron-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 therefore will analyze evidence based overstated concerns regarding serious adverse events highlighting unnecessary interventions for minor, self-limiting infusion reactions, which infrequently occur with intravenous iron administration. Recent data for the use of IV iron in a variety of clinic situations will be reviewed including women with heavy uterine bleeding, pregnancy, bariatric surgery, inflammatory bowel disease, and restless legs syndrome. Briefly discussed is the new frontier of IV iron’s use in the prevention of acute (high altitude) mountain sickness. It is clear that in many clinical situations IV iron is a new and improved standard of care offering advantages over oral iron in efficacy, toxicity, and convenience to patients and health care providers.
Treatment of older patients with acute lymphoblastic leukemia
Authors: Gökbuget Nicola 
Published: December 2016

AbstractThe treatment of older patients with acute lymphoblastic leukemia (ALL) is an unmet medical need. With increasing age, ALL patients have a significantly lower clinical remission rate, higher early mortality, higher relapse rate, and poorer survival compared with younger patients. This is only partly explained by a higher incidence of poor prognostic factors in the older age group. Most importantly, intensive chemotherapy with or without stem cell transplantation (SCT) is less well tolerated in older patients. Some progress has been made with delivering age-adapted, moderately intensive chemotherapy protocols for Ph/BCR–ABL-negative ALL and combinations of tyrosine kinase inhibitors with chemotherapy in Ph/BCR–ABL-positive ALL. For the future, optimizing supportive care, introducing targeted therapies, novel immunotherapies, moderately intensified consolidation strategies, and reduced intensity SCT are promising approaches. Prospective clinical trials for older patients are urgently needed to test these approaches.
Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches
Authors: Meeks Shannon L. , Batsuli Glaivy 
Published: December 2016

Abstract
The immune response to infused factor concentrates remains a major source of morbidity and mortality in the treatment of patients with hemophilia A and B. This review focuses on current treatment options and novel therapies currently in clinical trials. After a brief review of immune tolerance regimens, the focus of the discussion is on preventing bleeding in patients with hemophilia and inhibitors. Recombinant factor VIIa and activated prothrombin complex concentrates are the mainstays in treating bleeds in patients with inhibitors. Both agents have been shown to reduce bleeding episodes to a similar degree when infused prophylactically; however, individual patients may respond better to one agent over the other at any given time. The international immune tolerance trial revealed that a high-dose factor VIII regimen provided significantly better bleeding protection than the low-dose regimen. Given the high cost of treatment and the potential for a high-dose immune tolerance regimen to prevent bleeding in some patients, we discuss how we treat patients to maximize the prevention of bleeds while minimizing cost. Novel approaches to treatment of these patients are in development. These include agents that mimic factor VIII or augment thrombin generation by bypassing the inhibitor, as well as agents that inhibit the natural anticoagulants.