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Expert Review of Hematology

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https://www.readbyqxmd.com/read/28504024/detection-of-driver-and-subclonal-mutations-in-myelofibrosis-clinical-impact-on-pharmacologic-and-transplant-based-treatment-strategies
#1
Maria Chiara Finazzi, Federico Lussana, Silvia Salmoiraghi, Orietta Spinelli, Alessandro Rambaldi
Myelofibrosis (MF) is the most aggressive form among Philadelphia negative (Ph-) myeloproliferative neoplasms (MPNs). In the last years, the mutational landscape of MF has expanded remarkably by the identification of additional recurrent mutations, called subclonal mutations. Areas covered: Here we describe the available data about the currently identified subclonal mutations and their prognostic value in MF patients. We also review the practical value of including such molecular information in available prognostic models for both outcome prediction and possibly treatment decision with regards to transplant indication...
May 25, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28471695/current-use-and-potential-role-of-procalcitonin-in-the-diagnostic-work-up-and-follow-up-of-febrile-neutropenia-in-hematological-patients
#2
Benedetto Bruno, Alessandro Busca, Stefano Vallero, Stefania Raviolo, Nicola Mordini, Luca Nassi, Alessandro Cignetti, Ernesta Audisio, Moreno Festuccia, Alessandra Corsetti, Lorella Depaoli, Maura Faraci, Concetta Micalizzi, Silvia Corcione, Massimo Berger, Francesco Saglio, Paola Caropreso, Giulio Mengozzi, Vincenzo Squadrone, Francesco Giuseppe De Rosa, Luisa Giaccone
Febrile neutropenia (FN) represents a life-threatening complication in hematological malignancies. Its etiology is most often due to infections even though FN of other origins, such as tumor-related fever and non-infectious inflammation, should rapidly be ruled out. Initially, C-reactive protein and, more recently, procalcitonin (PCT) have been proposed as useful biomarkers for differential diagnosis. PCT was shown to be a good biomarker of bacterial infections and their clinical outcomes. Definition of standard cut-offs and design of PCT-guided treatment protocols remain however to be defined...
May 24, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28511567/treating-the-chronic-phase-chronic-myeloid-leukemia-patient-which-tki-when-to-switch-and-when-to-stop
#3
Ami B Patel, Brandon W Wilds, Michael W Deininger
With the discovery of imatinib mesylate nearly 20 years ago, tyrosine kinase inhibitors (TKIs) were found to be effective in chronic myeloid leukemia (CML). TKI therapy has since revolutionized the treatment of CML and has served as a paradigm of success for targeted drug therapy in cancer. Several new TKIs for CML have been approved over the last two decades that exhibit improved potency over imatinib and have different off-target profiles, providing options for individualized therapy selection. Areas covered: Current management of chronic phase CML, including guidance on the sequential use of imatinib and newer-generation TKIs and evolving treatment strategies such as TKI discontinuation...
May 22, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28482712/heme-mediated-cell-activation-the-inflammatory-puzzle-of-sickle-cell-anemia
#4
Caroline Conceição da Guarda, Rayra Pereira Santiago, Luciana Magalhães Fiuza, Milena Magalhães Aleluia, Júnia Raquel Dutra Ferreira, Camylla Vilas Boas Figueiredo, Setondji Cocou Modeste Alexandre Yahouedehou, Rodrigo Mota de Oliveira, Isa Menezes Lyra, Marilda de Souza Gonçalves
Hemolysis triggers the onset of several clinical manifestations of sickle cell anemia (SCA). During hemolysis, heme, which is derived from hemoglobin (Hb), accumulates due to the inability of detoxification systems to scavenge sufficiently. Heme exerts multiple harmful effects, including leukocyte activation and migration, enhanced adhesion molecule expression by endothelial cells and the production of pro-oxidant molecules. Area covered: In this review, we describe the effects of heme on leukocytes and endothelial cells, as well as the features of vascular endothelial cells related to vaso-occlusion in SCA...
May 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28480766/follicular-lymphomas-and-their-transformation-past-and-current-research
#5
Miriam Mendez, Maria Torrente, Mariano Provencio
Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL). Histological transformation (HT) refers to the evolution of a clinically indolent NHL to a clinically aggressive one, defined as those lymphomas in which survival is limited to a few months when untreated. Areas covered: HT is associated with rapid progression of lymphadenopathy, infiltration of extranodal sites, development of systemic symptoms, and elevated serum level of lactate dehydrogenase (LDH). It is frequently related to a poor prognosis, and the median survival after transformation is less than 2 years...
May 16, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28504554/how-is-patient-care-for-multiple-myeloma-advancing
#6
Sonja Genadieva Stavric, Francesca Bonello, Sara Bringhen, Mario Boccadoro, Alessandra Larocca
Treatment of multiple myeloma has undergone profound changes in the past years thanks to the increased understanding of the biology of the disease and the new treatment options. New drugs and effective approaches are currently available for the treatment of multiple myeloma, including immunomodulatory agents, proteasome inhibitors and autologous stem cell transplantation. Areas covered. We have described the recent updated criteria to start treatment in multiple myeloma and summarized clinical data from major studies including most recent agents...
May 15, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28503958/neonatal-management-and-outcome-in-alloimmune-hemolytic-disease
#7
Isabelle M C Ree, Vivianne E H J Smits-Wintjens, Johanna G van der Bom, Jeanine M M van Klink, Dick Oepkes, Enrico Lopriore
Hemolytic disease of the fetus and newborn (HDFN) occurs when fetal and neonatal erythroid cells are destroyed by maternal erythrocyte alloantibodies, it leads to anemia and hydrops in the fetus, and hyperbilirubinemia and kernicterus in the newborn. Postnatal care consists of intensive phototherapy and exchange transfusions to treat severe hyperbilirubinemia and top-up transfusions to treat early and late anemia. Other postnatal complications have been reported such as thrombocytopenia, iron overload and cholestasis requiring specific management...
May 13, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28475434/enhancing-acute-myeloid-leukemia-therapy-monitoring-response-using-residual-disease-testing-as-a-guide-to-therapeutic-decision-making
#8
Benjamin Tomlinson, Hillard M Lazarus
Current standards for monitoring the response of acute myeloid leukemia (AML) are based on morphologic assessments of the bone marrow and recovery of peripheral blood counts. A growing experience is being developed to enhance the detection of small amounts of AML, or minimal residual disease (MRD). Areas covered: Available techniques include multi-color flow cytometry (MFC) of leukemia associated immunophenotypes (LAIP), quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) for detecting fusion and mutated genes (RUNX1-RUNX1T1, CBFB-MYH11, and NPM1), overexpression of genes such as WT1, and next generation sequencing (NGS) for MRD...
May 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28460542/hematological-disorders-at-birth-in-complicated-monochorionic-twins
#9
Lianne Verbeek, Femke Slaghekke, Marieke Sueters, Johanna M Middeldorp, Frans J Klumper, Monique C Haak, Dick Oepkes, Enrico Lopriore
Monochorionic twins are at risk of severe complications including twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS) and acute peripartum TTTS. The pathophysiology is based on inter-twin blood transfusion through placental vascular anastomoses. Areas covered: This review focuses on the incidence, management and outcome of neonatal hematological complications at birth in TTTS, TAPS and acute peripartum TTTS. Expert commentary: Hematological disorders are often present at birth in monochorionic twins and include acute or chronic anemia, polycythemia and thrombocytopenia...
May 10, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28395546/post-transplant-cyclophosphamide-a-promising-anti-graft-versus-host-disease-prophylaxis-where-do-we-stand
#10
Alberto Mussetti, Raffaella Greco, Jacopo Peccatori, Paolo Corradini
Post transplant cyclophosphamide (PT/Cy) in association to other immunosuppressive agents or alone has emerged as a promising pharmacological strategy in the setting of allogeneic hematopoietic cell transplant (allo-HCT). Its safety profile and effectiveness in reducing GvHD (acute GvHD incidence comprised between 15 and 30%, chronic GvHD 20-30% in the haploidentical setting) contributed to the spreading of this technique all over the world. Areas covered: This review summarizes the use of PT/Cy in the setting of allo-HCT, both for oncological and non-malignant hematological diseases...
May 5, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28468596/multiple-viral-infections-in-primary-effusion-lymphoma-a-model-of-viral-cooperation-in-lymphomagenesis
#11
Annunziata Gloghini, Chiara C Volpi, Ambra V Gualeni, Riccardo Dolcetti, Italia Bongarzone, Paolo De Paoli, Antonino Carbone
Primary effusion lymphoma (PEL) is a rare B-cell lymphoid neoplasm mainly associated with HIV infection, presenting as pleural, peritoneal, and pericardial effusions. A defining property of PEL is its consistent association with Kaposi sarcoma associated herpesvirus (KSHV) infection, and, in most cases, Epstein Barr virus (EBV) co-infection. On these grounds, a review of the literature related to viral cooperation and lymphomagenesis can help to understand the complex interplay between KSHV and EBV in PEL pathogenesis...
May 4, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28452257/updates-on-the-pathophysiology-and-treatment-of-aplastic-anemia-a-comprehensive-review
#12
Prajwal Chaitanya Boddu, Tapan Mahendra Kadia
The past decade or longer has witnessed an acceleration in our understanding of previously developed immune system and clonal evolution mechanisms, and the genesis of more novel concepts of telomere attrition. Many of these concepts are steadily finding their way into translation in various aspects of clinical practice, and provide prospects to improve AA management and inform therapeutic strategy development. In this review, we intend to discuss the pathophysiology and treatments with an emphasis on most recent developments to provide an update on our understanding of disease mechanisms...
April 28, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28448199/deferiprone-for-the-treatment-of-transfusional-iron-overload-in-thalassemia
#13
Janet L Kwiatkowski, Ami Belmont
Transfusional iron overload can lead to hepatic fibrosis, arrhythmias and congestive heart failure and a number of endocrinopathies. Deferiprone is an oral iron chelator recently approved for use in the United States as a second line agent for the treatment of transfusional iron overload in patients with thalassemia. Areas covered: This article will review the data regarding the efficacy of deferiprone for iron chelation and prevention and reversal of iron related complications, the drug's adverse effect profile, and the use of this drug in combination regimens...
April 27, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28448172/the-macrophage-stimulating-anti-cancer-agent-rrx-001-protects-against-ischemia-reperfusion-injury
#14
Pedro Cabrales, Scott Caroen, Arnold Oronsky, Corey Carter, Jane Trepel, Thomas Summers, Tony Reid, Neil Oronsky, Michelle Lybeck, Bryan Oronsky
Introduction RRx-001, a clinical macrophage-stimulating anti-cancer agent that also produces nitric oxide (NO) was studied in a model of ischemia-reperfusion injury. Methods The production of NO is dependent on the oxygen tension because nitric oxide synthases convert l-arginine to NO and l-citrulline in the presence of O2. Since the P450 enzymes, which metabolize nitrate esters such as nitroglycerin are dependent on oxygen, the generation of 'exogenous' NO is also sensitive to alterations in tissue PO2. I/R injury was studied in a hamster chamber window, with compression of the periphery of the window for 1 hour to induce ischemia...
April 27, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28395559/management-of-myelofibrosis-jak-inhibition-and-beyond
#15
Maximilian Stahl, Amer M Zeidan
Myelofibrosis (MF) is characterized by bone marrow fibrosis with subsequent extramedullary hematopoiesis and abnormal cytokine expression leading to splenomegaly, constitutional symptoms and cytopenias. The discovery of the JAK2 V617F mutation in the majority of MF patients has been followed by significant progress in drug development for MF. Areas covered: In this article, we review advances in the understanding of the underlying disease biology, prognostic assessment and therapeutic modalities for MF. We provide clinical trial evidence behind using the JAK2 inhibitor ruxolitinib, erythropoiesis stimulating agents, androgens, immunomodulatory drugs, interferon, cytoreductive drugs and hypomethylating agents in MF...
April 26, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28395545/lymphoma-classification-update-b-cell-non-hodgkin-lymphomas
#16
Manli Jiang, N Nora Bennani, Andrew L Feldman
Lymphomas are classified based on the normal counterpart, or cell of origin, from which they arise. Because lymphocytes have physiologic immune functions that vary both by lineage and by stage of differentiation, the classification of lymphomas arising from these normal lymphoid populations is complex. Recent genomic data have contributed additional complexity. Areas covered: Lymphoma classification follows the World Health Organization (WHO) system, which reflects international consensus and is based on pathological, genetic, and clinical factors...
April 24, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28388244/which-therapies-will-move-to-the-front-line-for-multiple-myeloma
#17
María J Cejalvo, Javier de la Rubia
Despite substantial progress, multiple myeloma (MM) remains an incurable disease. Recently the availability of several novel drugs with different and innovative mechanisms of action (daratumumab, elotuzumab, carfilzomib, ixazomib, and panobinostat) has increased the therapeutic options but has also increased complexity in the management of patients with MM. Areas covered: The outstanding results observed in the relapsed setting with regimens including these new drugs has provided the investigators with several treatment options that are being tested also in patients with newly diagnosed MM...
April 24, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28374619/super-resolution-microscopy-in-the-diagnosis-of-platelet-granule-disorders
#18
Alex E Knight, Keith Gomez, Daniel F Cutler
Platelet granule deficiencies lead to bleeding disorders, but their specific diagnosis typically requires whole mount transmission electron microscopy, which is often not available and has a number of important limitations. We recently proposed the use of advanced forms of fluorescence microscopy - the so-called 'super-resolution' microscopies - as a possible solution. Areas covered: In this special report, we review the diagnosis of platelet granule deficiencies, and discuss how recent developments in fluorescence microscopy may be useful in improving diagnostic approaches to these and related disorders...
April 13, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28402197/minimal-residual-disease-or-cure-in-mpns-rationales-and-perspectives-on-combination-therapy-with-interferon-alpha2-and-ruxolitinib
#19
Mads Emil Bjørn, Hans Carl Hasselbalch
The therapeutic landscape of the Philadelphia-negative myeloproliferative neoplasms (MPNs) is markedly changing consequent to the development of JAK-inhibitors and the use of ruxolitinib (RUX) in patients with myelofibrosis (MF) and patients with polycythemia vera (PV) who develop refractoriness or intolerance to hydroxyurea. The use of Interferon-alpha2 (IFN) is rapidly expanding in several countries, based upon favourable safety and efficacy profiles in several single-arm studies during the last 30 years, displaying complete hematological remissions in a large proportion of patients, a reduction in the JAK2V617 F and CALR mutational burden and in a subset of patients with PV with normalisation of the bone marrow after long-term treatment - even being sustained for several years after discontinuation of IFN...
April 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28402148/should-modulation-of-p50-be-a-therapeutic-target-in-the-critically-ill
#20
Amudan J Srinivasan, Clare Morkane, Daniel S Martin, Ian J Welsby
A defining feature of human hemoglobin is its oxygen binding affinity, quantified by the partial pressure of oxygen at which hemoglobin is 50% saturated (p50), and the variability of this parameter over a range of physiological and environmental states. Modulation of this property of hemoglobin can directly affect the degree of peripheral oxygen offloading and tissue oxygenation. Areas covered: This review summarizes the role of hemoglobin oxygen affinity in normal and abnormal physiology and discusses the current state of the literature regarding artificial modulation of p50...
April 12, 2017: Expert Review of Hematology
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