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Therapeutic Advances in Hematology

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https://www.readbyqxmd.com/read/30013767/a-case-series-of-kimura-s-disease-a-diagnostic-challenge
#1
Vivek Kumar, Navneet Mittal, Yiwu Huang, Jasminka Balderracchi, Huo Xiang Zheng, Zujin Li, Yiqing Xu
Kimura's disease (KD) is a rare, benign disorder characterized by subcutaneous masses with regional lymph-node enlargement. It is considered to be due to chronic inflammation of unclear etiology. Most cases have been reported in young, 20-30-year-old men of Asian descent. The diagnosis of KD is based on pathological features and elevated immunoglobulin E levels. Characteristic pathological features include intact lymph-node architecture, florid germinal center hyperplasia, extensive eosinophilic infiltrates, and proliferation of postcapillary venules...
July 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/30013766/bay-81-8973-a-full-length-recombinant-factor-viii-for-the-treatment-of-hemophilia-a-product-review
#2
REVIEW
Johnny N Mahlangu, Sanjay P Ahuja, Jerzy Windyga, Nikki Church, Anita Shah, Lawrence Schwartz
BAY 81-8973 (Kovaltry® ) is an unmodified, full-length recombinant factor VIII (rFVIII) approved for the prevention and treatment of bleeding episodes in patients with hemophilia A. The amino acid sequence for BAY 81-8973 is identical to that of sucrose-formulated rFVIII (rFVIII-FS; Kogenate® FS/KOGENATE® , Bayer), but the two products differ in their manufacturing approaches. The manufacture of BAY 81-8973 includes several modifications and enhancements, such as the introduction of the gene for human heat shock protein 70, a molecular chaperone protein that facilitates folding of proteins; no addition of human- or animal-derived proteins in the cell culture, purification process, or final formulation; and use of a 20-nm filter to remove any potential aggregates and pathogens...
July 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/30013765/update-on-the-role-of-lenalidomide-in-patients-with-multiple-myeloma
#3
REVIEW
Sarah A Holstein, Vera J Suman, Philip L McCarthy
Lenalidomide is a derivative of thalidomide and belongs to the class of drugs known as the immunomodulatory drugs (IMiDs). The IMiDs have played a large role in improving the survival outcomes of patients with multiple myeloma. In particular, lenalidomide is currently standard of care in the newly diagnosed setting, in the maintenance setting post-autologous stem cell transplant, as well as in the relapsed/refractory setting. While the combination of lenalidomide and various proteasome inhibitors has proven particularly effective, there are emerging data demonstrating the effectiveness of lenalidomide in combination with other important classes of drugs including the monoclonal antibodies...
July 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/30013764/the-role-of-enasidenib-in-the-treatment-of-mutant-idh2-acute-myeloid-leukemia
#4
REVIEW
Iman Abou Dalle, Courtney D DiNardo
Recurrent mutations affecting cellular metabolism and epigenetic regulation are implicated in the pathogenesis of acute myeloid leukemia (AML). Isocitrate dehydrogenase 2 ( IDH2 ) gene mutations are described in 12% of patients with AML and 5% of patients with myelodysplastic syndromes. IDH2 enzyme is involved in the Krebs cycle, catalyzing α-ketoglutarate from isocitrate. Mutant IDH2 enzymes acquire a neomorphic enzymatic activity with the ability to produce 2-hydroxyglutarate from α-ketoglutarate, inhibiting multiple α-ketoglutarate-dependent dioxygenase reactions; leading to aberrant DNA hypermethylation and differentiation block in myeloid precursors and ultimately promoting leukemogenesis...
July 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29899890/pharmacokinetic-based-prediction-of-real-life-dosing-of-extended-half-life-clotting-factor-concentrates-on-hemophilia
#5
REVIEW
Massimo Morfini, Stefano Gherardini
The improvement of clotting factor concentrates (CFCs) has undergone an impressive boost during the last six years. Since 2010, several new recombinant factor (rF)VIII/IX concentrates entered phase I/II/III clinical trials. The improvements are related to the culture of human embryonic kidney (HEK) cells, post-translational glycosylation, PEGylation, and co-expression of the fragment crystallizable (Fc) region of immunoglobulin (Ig)G1 or albumin genes in the manufacturing procedures. The extended half-life (EHL) CFCs allow an increase of the interval between bolus administrations during prophylaxis, a very important advantage for patients with difficulties in venous access...
June 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29899889/acute-myeloid-leukemia-chimeric-antigen-receptor-t-cell-immunotherapy-how-far-up-the-road-have-we-traveled
#6
REVIEW
Sarah K Tasian
Chemotherapy resistance and relapse remain significant sources of mortality for children and adults with acute myeloid leukemia (AML). Further intensification of conventional cytotoxic chemotherapy is likely not feasible due to the severity of acute and long-term side effects upon normal tissues commonly induced by these drugs. Successful development and implementation of new precision medicine treatment approaches for patients with AML, which may improve leukemia remission and diminish toxicity, is thus a major priority...
June 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29713445/the-evolution-of-stem-cell-transplantation-in-multiple-myeloma
#7
REVIEW
Sarakshi Mahajan, Nidhi Tandon, Shaji Kumar
Autologous stem-cell transplantation (ASCT) remains an integral part of treatment for previously untreated, and may have value in the treatment of relapsed patients with, multiple myeloma (MM). The addition of novel agents like immunomodulators and proteasome inhibitors as induction therapy before and as consolidation/maintenance therapy after ASCT has led to an improvement in complete response (CR) rates, progression-free survival (PFS) and overall survival (OS). With advances in supportive care, older patients and patients with renal insufficiency are now able to safely undergo the procedure...
May 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29713444/personalizing-initial-therapy-in-acute-myeloid-leukemia-incorporating-novel-agents-into-clinical-practice
#8
REVIEW
Christin B DeStefano, Christopher S Hourigan
While the past decade has seen a revolution in understanding of the genetic and molecular etiology of the disease, in clinical practice, initial therapy for acute myeloid leukemia (AML) patients has been a relatively straightforward choice between intensive combination cytotoxic induction therapy as used for decades or less-intensive hypomethylating therapy. The year 2017, however, witnessed US Food and Drug Administration approvals of midostaurin, enasidenib, gemtuzumab ozogamicin and CPX-351 for AML patients, with many other promising agents currently in clinical trials...
May 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29623180/pembrolizumab-and-its-role-in-relapsed-refractory-classical-hodgkin-s-lymphoma-evidence-to-date-and-clinical-utility
#9
REVIEW
Polina Shindiapina, Lapo Alinari
Immune evasion is a critical mechanism of malignant cell survival, and relies in part on molecular signaling through the programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1) axis that contributes to T cell exhaustion. Immune modulatory therapy with monoclonal antibodies against PD-1 designed to enhance antitumor immune response have shown promise in the treatment of advanced solid tumors and hematologic malignancies. Classical Hodgkin's lymphoma (cHL), a unique B cell malignancy characterized by an extensive but ineffective immune cell infiltrate surrounding a small number of tumor cells, has shown significant response to anti-PD-1 directed therapy...
April 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29623179/co-expression-of-myc-and-bcl2-predicts-poorer-outcomes-for-relapsed-refractory-diffuse-large-b-cell-lymphoma-with-r-ice-and-intent-to-transplant
#10
Joshua Allen, Ana Lucia Ruano Mendez, Lisa Rybicki, Yazeed Sawalha, Deepa Jagadeesh, Robert Dean, Brad Pohlman, Mitchell R Smith, Eric D Hsi, Brian T Hill
Diffuse large B-cell lymphoma (DLBCL) with co-expression of MYC and BCL2 protein by immunohistochemistry (IHC) - that is, double-expresser lymphoma (DEL) - is associated with poor outcomes after standard frontline therapy. Less is known about the prognostic impact of DEL in patients with relapsed/refractory disease treated with salvage therapy and autologous stem cell transplantation (ASCT). We analyzed the outcomes of 167 patients with relapsed/refractory DLBCL treated with R-ICE (rituximab, ifosfamide, carboplatin and etoposide), of whom 111 patients (66%) underwent ASCT...
April 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29531660/safety-and-efficacy-of-nilotinib-in-routine-clinical-practice-in-patients-with-chronic-myeloid-leukemia-in-chronic-or-accelerated-phase-with-resistance-or-intolerance-to-imatinib-results-from-the-novel-study
#11
Ching-Yuan Kuo, Po-Nan Wang, Wen-Li Hwang, Cheng-Hwai Tzeng, Li-Yaun Bai, Jih-Luh Tang, Ming-Chih Chang, Sheng-Fung Lin, Tsai-Yun Chen, Yeu-Chin Chen, Tran-Der Tan, Chih-Yi Hsieh, Chinjune Lin, Clinton Lai, Darko Miljkovic, Cheng-Shyong Chang
Background: Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), is approved for the treatment of patients with chronic myeloid leukemia (CML) in many countries, including Taiwan. Though a number of controlled clinical trials have demonstrated the safety and efficacy of nilotinib, studies assessing the safety and efficacy of nilotinib in routine clinical practice are limited. Methods: The current study was an open-label, single-arm study conducted across 12 centers in Taiwan in adult patients with CML in chronic or accelerated phase with confirmed Ph+ chromosome (or BCR-ABL) and resistant or intolerant to one or more previous TKIs...
March 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29387330/novel-therapies-and-current-clinical-progress-in-hemophilia-a
#12
REVIEW
Pauline Balkaransingh, Guy Young
The evolution of hemophilia treatment and care is a fascinating one but has been fraught with many challenges at every turn. Over the last 50 years or so patients with hemophilia and providers have witnessed great advances in the treatment of this disease. With these advances, there has been a dramatic decrease in the mortality and morbidity associated with hemophilia. Even with the remarkable advancements in treatment, however, new and old challenges continue to plague the hemophilia community. The cost of factor replacement and the frequency of infusions, especially in patients with severe hemophilia on prophylaxis, remains a significant challenge for this population...
February 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29317998/new-and-emerging-therapies-for-acute-and-chronic-graft-versus-host-disease
#13
REVIEW
LaQuisa Hill, Amin Alousi, Partow Kebriaei, Rohtesh Mehta, Katayoun Rezvani, Elizabeth Shpall
Graft versus host disease (GVHD) remains a major cause of morbidity and mortality following allogeneic hematopoietic stem-cell transplantation (HSCT). Despite the use of prophylactic GVHD regimens, a significant proportion of transplant recipients will develop acute or chronic GVHD following HSCT. Corticosteroids are standard first-line therapy, but are only effective in roughly half of all cases with ~50% of patients going on to develop steroid-refractory disease, which increases the risk of nonrelapse mortality...
January 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29317997/experience-with-ibrutinib-for-first-line-use-in-patients-with-chronic-lymphocytic-leukemia
#14
REVIEW
Gilad Itchaki, Jennifer R Brown
Ibrutinib is the first in-class, orally administered, Bruton's tyrosine kinase (BTK) inhibitor that abrogates the critical signaling downstream of the B-cell receptor (BCR). This signaling is required for B-cell survival, proliferation and interaction with the microenvironment. Ibrutinib proved active in preclinical models of lymphoproliferative diseases and achieved impressive response rates in heavily pretreated relapsed and refractory (R/R) patients with chronic lymphocytic leukemia (CLL). Ibrutinib prolonged survival compared to standard therapy and mitigated the effect of most poor prognostic factors in CLL, thus becoming the main therapeutic option in high-risk populations...
January 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29204262/the-role-of-oral-anticoagulant-therapy-in-patients-with-acute-coronary-syndrome
#15
REVIEW
Jae Youn Moon, Deepa Nagaraju, Francesco Franchi, Fabiana Rollini, Dominick J Angiolillo
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist represents the current standard of care to prevent atherothrombotic recurrences in patients with acute coronary syndrome (ACS). However, despite the use of DAPT, the recurrence rate of cardiovascular ischemic events still remains high. This persistent risk may be in part attributed to the sustained activation of the coagulation cascade leading to generation of thrombin, which may continue to play a key role in thrombus formation. The use of vitamin K antagonists (VKAs) as a strategy to reduce atherothrombotic recurrences after an ACS has been previously tested, leading to overall unfavorable outcomes due to the high risk of bleeding complications...
December 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29204261/recombinant-human-factor-viia-rfviia-in-hemophilia-mode-of-action-and-evidence-to-date
#16
REVIEW
Muriel Giansily-Blaizot, Jean-François Schved
Recombinant activated factor VII (rFVIIa) is a bypassing agent widely used both in the treatment and prevention of hemorrhagic complications due to hemophilia with inhibitor. In such cases, antihemophilic factors cannot be used. The normal physiology of factor VII/ factor VIIa (FVII/FVIIa) in the hemostatic process requires the presence of tissue factor (TF) that links to FVII leading to a FVIIa-TF complex which activates both factor X and factor IX. The therapeutic use of rFVIIa requires high amount of FVIIa...
December 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29204260/the-evolving-role-of-targeted-biological-agents-in-the-management-of-indolent-b-cell-lymphomas
#17
REVIEW
Trent Peng Wang, John Harwood Scott, Stefan Klaus Barta
Improved understanding of the mechanisms of lymphomagenesis has resulted in a surge of development for new targeted agents. An impressive number of biological agents targeting different steps in the pathways of tumor proliferation, survival and apoptosis have become available. The management of patients with indolent non-Hodgkin lymphomas (iNHLs) is rapidly transforming with incorporation of those targeted biological agents into the front-line and relapsed/refractory setting. This review highlights several categories of novel biological agents and will discuss their potential role in the contemporary management of patients with iNHLs...
December 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29093807/biological-and-clinical-implications-of-telomere-dysfunction-in-myeloid-malignancies
#18
REVIEW
Ashwin Kishtagari, Justin Watts
Telomeres at the ends of linear chromosomes protect the genome. Telomeres shorten with each round of cell division, placing a finite limit on cell growth. Telomere attrition is associated with cell senescence and apoptosis. Telomerase, a specialized ribonucleoprotein complex, maintains telomeres homeostasis through repeat addition of telomere sequences to the 3' telomeric overhang. Telomere biology is closely related to cancer and normal aging. Upregulation of telomerase or activation of the alternative pathway of telomere lengthening is a hallmark of cancer cells, making telomerase an attractive target for cancer therapeutics...
November 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29051801/current-and-emerging-factor-viii-replacement-products-for-hemophilia-a
#19
REVIEW
Lorraine A Cafuir, Christine L Kempton
Hemophilia A is a congenital X-linked bleeding disorder caused by coagulation factor VIII (FVIII) deficiency. Routine infusion of factor replacement products is the current standard of care; however, the development of alloantibodies against FVIII remains a challenge. The treatment of hemophilia has undergone major advances over the past century to improve safety, effectiveness, manufacturing, and convenience of factor products. Major recent advances in the treatment of hemophilia A include the emergence of extended half-life products, factor VIII orthologs, and gene therapy products...
October 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29051800/current-strategies-for-salvage-treatment-for-relapsed-classical-hodgkin-lymphoma
#20
REVIEW
Liana Nikolaenko, Robert Chen, Alex F Herrera
Hodgkin lymphoma (HL) is curable in 70-80% of patients with first-line therapy. However, relapses occur in a minority of patients with favorable early stage disease and are more frequent in patients with advanced HL. Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) for patients with chemotherapy-sensitive disease is a standard treatment sequence for relapsed or refractory (rel/ref) HL. Patients who achieve complete response prior to ASCT have better survival outcomes...
October 2017: Therapeutic Advances in Hematology
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