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Blood Reviews

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https://www.readbyqxmd.com/read/30005817/rationale-for-assessing-the-therapeutic-potential-of-resveratrol-in-hematological-malignancies
#1
REVIEW
J Luis Espinoza, Yu Kurokawa, Akiyoshi Takami
Promising results from pre-clinical studies on the naturally-occurring polyphenol resveratrol have generated considerable interest and somewhat excessive expectations regarding the therapeutic potential of this compound for treating or preventing various diseases, including cardiovascular and neurodegenerative disorders and cancer. Resveratrol has potent inhibitory activity in vitro against various tumor types, including cell lines derived from virtually all blood malignancies. Pharmacological studies have shown that resveratrol is safe for humans but has poor bioavailability, due to its extensive hepatic metabolism...
July 5, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29857920/increased-bone-resorption-in-hemophilia
#2
REVIEW
E Carlos Rodriguez-Merchan, Leonard A Valentino
In patients with hemophilia, osteoporosis is frequently observed for which the etiology remains unclear. The aim of this paper is to review the available experimental evidence indicating the presence of this disorder in patients with hemophilia, explore the potential mechanisms which may lead to reduced bone mineral density (BMD) and speculate on useful interventions to circumvent it. A narrative review of the English literature up to April 2018 was performed. The available evidence demonstrates an increased rate of bone resorption and an excess of osteoporosis among patients with hemophilia...
May 25, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29866493/the-evolving-understanding-of-factor-viii-binding-sites-and-implications-for-the-treatment-of-hemophilia-a
#3
REVIEW
Gary E Gilbert
Hemophilia A is caused by decreased or dysfunctional blood coagulation factor VIII (FVIII). Recent developments in the understanding of FVIII biology, in particular the nature of FVIII binding sites on platelets, may provide new insight into the limitations of current assays. Recent data suggest that the phospholipid vesicles, which represent nonphysiologic membranes of high phosphatidylserine (PS) content, poorly reflect functional FVIII binding sites critical to coagulation. This narrative review describes the function of FVIII in clotting and discusses our evolving understanding of FVIII binding sites and their clinical implications...
May 24, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29728319/current-status-and-trends-in-the-diagnostics-of-aml-and-mds
#4
REVIEW
Evgenii Shumilov, Johanna Flach, Alexander Kohlmann, Yara Banz, Nicolas Bonadies, Martin Fiedler, Thomas Pabst, Ulrike Bacher
Diagnostics of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) have recently been experiencing extensive modifications regarding the incorporation of next-generation sequencing (NGS) strategies into established diagnostic algorithms, classification and risk stratification systems, and minimal residual disease (MRD) detection. Considering the increasing arsenal of targeted therapies (e.g. FLT3 or IDH1/IDH2 inhibitors) for AML, timely and comprehensive molecular mutation screening has arrived in daily practice...
April 27, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29482895/bispecific-antibody-based-therapeutics-strengths-and-challenges
#5
REVIEW
Archana Thakur, Manley Huang, Lawrence G Lum
Monoclonal antibody-based targeted therapy has greatly improved treatment options for patients. However, long-term efficacy of such antibodies is limited by resistance mechanisms. New insights into the mechanisms by which tumors evade immune control have driven innovative therapeutic strategies to eliminate cancer by re-directing immune cells to tumors. Advances in protein engineering technology have generated multiple bispecific antibody (BsAb) formats capable of targeting multiple antigens as a single agent...
July 2018: Blood Reviews
https://www.readbyqxmd.com/read/29482894/review-of-immune-tolerance-induction-in-hemophilia-a
#6
REVIEW
S J Schep, R E G Schutgens, K Fischer, M L Boes
At first sight the bleeding disorder hemophilia A seems to have little in common with immune disorders, but immunology research intersects with other disciplines including hematology. Nowadays, the most important complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors) against exogenous administered factor VIII (FVIII), which occurs in approximately 30% of all patients with severe hemophilia A. This antibody response renders FVIII replacement therapy ineffective, thereby increasing the risk for uncontrollable bleeding and morbidity, decreasing quality of life and increasing healthcare costs...
July 2018: Blood Reviews
https://www.readbyqxmd.com/read/29475779/anti-cancer-vaccine-therapy-for-hematologic-malignancies-an-evolving-era
#7
REVIEW
Myrna R Nahas, Jacalyn Rosenblatt, Hillard M Lazarus, David Avigan
The potential promise of therapeutic vaccination as effective therapy for hematologic malignancies is supported by the observation that allogeneic hematopoietic cell transplantation is curative for a subset of patients due to the graft-versus-tumor effect mediated by alloreactive lymphocytes. Tumor vaccines are being explored as a therapeutic strategy to re-educate host immunity to recognize and target malignant cells through the activation and expansion of effector cell populations. Via several mechanisms, tumor cells induce T cell dysfunction and senescence, amplifying and maintaining tumor cell immunosuppressive effects, resulting in failure of clinical trials of tumor vaccines and adoptive T cell therapies...
July 2018: Blood Reviews
https://www.readbyqxmd.com/read/29455932/a-paradigm-shift-on-beta-thalassaemia-treatment-how-will-we-manage-this-old-disease-with-new-therapies
#8
REVIEW
Maria Domenica Cappellini, John B Porter, Vip Viprakasit, Ali T Taher
Beta-thalassaemia causes defective haemoglobin synthesis leading to ineffective erythropoiesis, chronic haemolytic anaemia, and subsequent clinical complications. Blood transfusion and iron chelation allow long-term disease control, and haematopoietic stem cell transplantation offers a potential cure for some patients. Nonetheless, there are still many challenges in the management of beta-thalassaemia. The main treatment option for most patients is supportive care; furthermore, the long-term efficacy and safety of current therapeutic strategies are limited and adherence is suboptimal...
July 2018: Blood Reviews
https://www.readbyqxmd.com/read/29454474/cardiovascular-pulmonary-and-metabolic-toxicities-complicating-tyrosine-kinase-inhibitor-therapy-in-chronic-myeloid-leukemia-strategies-for-monitoring-detecting-and-managing
#9
REVIEW
Bruno C Medeiros, Jennifer Possick, Michael Fradley
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, the incidence of which increases with age. Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment, including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib. Beyond matching patient disease profiles with TKI specificity, differences in the efficacy and toxicity profiles and a patient's comorbid risk factors should be considered when selecting the most appropriate agent. Our objectives are to review the incidence and severity of cardiovascular, metabolic, and pulmonary disorders associated with these TKIs, highlighting differences in adverse event profiles, suggested risk-mitigation strategies, and guidance for TKI selection in different settings...
July 2018: Blood Reviews
https://www.readbyqxmd.com/read/29426727/setting-the-stage-for-individualized-therapy-in-hemophilia-what-role-can-pharmacokinetics-play
#10
REVIEW
H C A M Hazendonk, I van Moort, R A A Mathôt, K Fijnvandraat, F W G Leebeek, P W Collins, M H Cnossen
Replacement therapy with clotting factor concentrates (CFC) is the mainstay of treatment in hemophilia. Its widespread application has led to a dramatic decrease in morbidity and mortality in patients, with concomitant improvement of quality of life. However, dosing is challenging and costs are high. This review discusses benefits and limitations of pharmacokinetic (PK)-guided dosing of replacement therapy as an alternative for current dosing regimens. Dosing of CFC is now primarily based on body weight and based on its in vivo recovery (IVR)...
July 2018: Blood Reviews
https://www.readbyqxmd.com/read/29402471/direct-oral-anticoagulant-use-in-patients-with-thrombophilia-antiphospholipid-syndrome-or-venous-thrombosis-of-unusual-sites-a-narrative-review
#11
REVIEW
Laurent Bertoletti, Ygal Benhamou, Yannick Béjot, Sylvestre Marechaux, Saida Cheggour, Boris Aleil, Nicolas Lellouche, Jean-Guillaume Dillinger, Aurélien Delluc
Direct oral anticoagulants (DOACs) are indicated in the treatment and prevention of venous thromboembolism (VTE). However, the use of DOACs in unusual VTE, including cerebral venous thrombosis (CVT) and splanchnic venous thrombosis (SVT), and in patients with biological thrombophilia including minor thrombophilia (Factor V Leiden and prothrombin G20210A), major innate thrombophilia (protein C and S deficiency, and antithrombin) and major acquired thrombophilia (antiphospholipid syndrome [APS]), remains controversial due to the paucity of available data...
July 2018: Blood Reviews
https://www.readbyqxmd.com/read/29397262/consequences-of-dysregulated-complement-regulators-on-red-blood-cells
#12
REVIEW
Astrid J F Thielen, Sacha Zeerleder, Diana Wouters
The complement system represents the first line of defense that is involved in the clearance of pathogens, dying cells and immune complexes via opsonization, induction of an inflammatory response and the formation of a lytic pore. Red blood cells (RBCs) are very important for the delivery of oxygen to tissues and are continuously in contact with complement proteins in the blood plasma. To prevent complement activation on RBCs, various complement regulatory proteins can be found in plasma and on the cell membrane...
July 2018: Blood Reviews
https://www.readbyqxmd.com/read/29306488/reintroduction-of-anticoagulant-therapy-after-intracranial-haemorrhage-if-and-when
#13
REVIEW
Martin Scott, Ryan Low, Dawn Swan, Jecko Thachil
Intracranial haemorrhage is a devastating complication of anticoagulation. In surviving patients, physicians will be faced with the dilemma of if and when treatment should be reintroduced. There is little evidence to support this decision making and guidelines refrain from making specific recommendations. Existing data relates almost exclusively to vitamin K antagonists and is entirely retrospective. There appears to be an overall benefit to reintroducing anticoagulation in most patients; although, this may not be advocated in those at the highest risk of recurrent bleeding...
May 2018: Blood Reviews
https://www.readbyqxmd.com/read/29289361/the-pathobiology-of-primary-testicular-diffuse-large-b-cell-lymphoma-implications-for-novel-therapies
#14
REVIEW
David D W Twa, Anja Mottok, Kerry J Savage, Christian Steidl
Primary testicular lymphomas (PTL) are the most prevalent type of testicular cancer arising in men over the age of 60. PTL accounts for approximately 1-2% of all non-Hodgkin lymphomas and most present with localized disease but despite this, outcome is poor. The majority of cases represent an extranodal manifestation of diffuse large B-cell lymphoma (DLBCL), known as primary testicular DLBCL (PT-DLBCL). Gene expression profiling has established that over 75% of PT-DLBCLs resemble the activated B-cell-like (ABC) or non-germinal center subtype of nodal DLBCL...
May 2018: Blood Reviews
https://www.readbyqxmd.com/read/29276026/dueling-for-dual-inhibition-means-to-enhance-effectiveness-of-pi3k-akt-mtor-inhibitors-in-aml
#15
REVIEW
Lauren Herschbein, Jane L Liesveld
The phosphatidylinositol 3-kinase/protein kinase B (Akt)/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway is amplified in 60-80% of patients with acute myelogenous leukemia (AML). Since this complex pathway is crucial to cell functions such as growth, proliferation, and survival, inhibition of this pathway would be postulated to inhibit leukemia initiation and propagation. Inhibition of the mTORC1 pathway has met with limited success in AML due to multiple resistance mechanisms including direct insensitivity of the mTORC1 complex, feedback activation of the PI3k/Akt signaling network, insulin growth factor-1 (IGF-1) activation of PI3K, and others...
May 2018: Blood Reviews
https://www.readbyqxmd.com/read/29223447/clinical-laboratory-and-imaging-findings-in-castleman-s-disease-the-subtype-decides
#16
REVIEW
Michael Haap, Julia Wiefels, Marius Horger, Annika Hoyer, Karsten Müssig
Castleman's disease (CD) is a rare lymphoproliferative disorder with its distinct unicentric (uCD) and multicentric (mCD) entities. The present work aimed at characterizing CD in more detail. From the 775 articles found by a PubMed search, 1133 cases were extracted. Two own cases were included. UCD was identified in 719 (42% males) and mCD in 416 (63% males) cases. Age in uCD was 34±17 and in mCD 48±18years. The hyaline-vascular type predominated in uCD and the plasma cell type in mCD. Clinical symptoms were more common in mCD...
May 2018: Blood Reviews
https://www.readbyqxmd.com/read/29198753/cell-therapies-for-hematological-malignancies-don-t-forget-non-gene-modified-t-cells
#17
REVIEW
Melanie L Grant, Catherine M Bollard
Cell therapy currently performs an important role in the treatment of patients with various hematological malignancies. The response to the cell therapy is regulated by multiple factors including the patient's immune system status, genetic profile, stage at diagnosis, age, and underlying disease. Cell therapy that does not require genetic manipulation can be mediated by donor lymphocyte infusion strategies, selective depletion in the post-transplant setting and the ex vivo expansion of antigen-specific T cells...
May 2018: Blood Reviews
https://www.readbyqxmd.com/read/29174416/unrelated-donor-umbilical-cord-blood-transplant-versus-unrelated-hematopoietic-stem-cell-transplant-in-patients-with-acute-leukemia-a-meta-analysis-and-systematic-review
#18
REVIEW
Xiao Lou, Chuanhua Zhao, Hu Chen
Acute leukemia is a global disease with a poor prognosis for many patients. While an increasing number of patients with acute leukemia are being treated with unrelated hematopoietic stem cell transplants (HSCT) or umbilical cord blood transplants (UCBT), recent comparative reports of these 2 procedures are lacking. Therefore, we conducted a meta-analysis of the safety and efficacy of unrelated HSCT and unrelated single-unit UCBT for the treatment of pediatric and adult patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML)...
May 2018: Blood Reviews
https://www.readbyqxmd.com/read/29157973/when-the-good-go-bad-mutant-npm1-in-acute-myeloid-leukemia
#19
REVIEW
Preethi Kunchala, Sudhakiranmayi Kuravi, Roy Jensen, Joseph McGuirk, Ramesh Balusu
Nucleophosmin 1 (NPM1) is a nucleolar phosphoprotein that performs diverse biological functions including molecular chaperoning, ribosome biogenesis, DNA repair, and genome stability. Acute myeloid leukemia (AML) is a heterogeneous disease, more than half of the AML cases exhibit normal karyotype (NK). Approximately 50-60 percent of patients with NK-AML carry NPM1 mutations which are characterized by cytoplasmic dislocation of the NPM1 protein. In AML, mutant NPM1 (NPM1c+) acts in a dominant negative fashion and also blocks the differentiation of myeloid cells through gain-of-function for the AML phenotype...
May 2018: Blood Reviews
https://www.readbyqxmd.com/read/29132746/diabetes-mellitus-as-a-poor-mobilizer-condition
#20
REVIEW
Gian Paolo Fadini, John F DiPersio
Hematopoietic stem cell (HSC) transplantation in an effective and curative therapy for numerous hematological malignancies. Mobilization of HSCs from bone marrow (BM) to peripheral blood (PB) followed by apheresis is the gold standard for obtaining HSCs for both autologous and allogeneic stem cell transplantation. After administration of granulocyte-colony stimulating factor (G-CSF), up to 30% of patients fail to mobilize "optimal" numbers of HSCs required for engraftment. This review summarizes the current experimental and clinical evidence that diabetes mellitus is a risk factor for poor mobilization...
May 2018: Blood Reviews
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