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Blood Reviews

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https://www.readbyqxmd.com/read/29455932/a-paradigm-shift-on-beta-thalassaemia-treatment-how-will-we-manage-this-old-disease-with-new-therapies
#1
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...
February 12, 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
#2
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...
February 3, 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
#3
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...
February 2, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29426727/setting-the-stage-for-individualized-therapy-in-hemophilia-what-role-can-pharmacokinetics-play
#4
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)...
January 31, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29397262/consequences-of-dysregulated-complement-regulators-on-red-blood-cells
#5
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...
January 31, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29306488/reintroduction-of-anticoagulant-therapy-after-intracranial-haemorrhage-if-and-when
#6
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...
December 20, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29289361/the-pathobiology-of-primary-testicular-diffuse-large-b-cell-lymphoma-implications-for-novel-therapies
#7
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...
December 20, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29276026/dueling-for-dual-inhibition-means-to-enhance-effectiveness-of-pi3k-akt-mtor-inhibitors-in-aml
#8
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...
December 2, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29223447/clinical-laboratory-and-imaging-findings-in-castleman-s-disease-the-subtype-decides
#9
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...
November 29, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29198753/cell-therapies-for-hematological-malignancies-don-t-forget-non-gene-modified-t-cells
#10
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...
November 27, 2017: 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
#11
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)...
November 15, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29132746/diabetes-mellitus-as-a-poor-mobilizer-condition
#12
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...
November 8, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29157973/when-the-good-go-bad-mutant-npm1-in-acute-myeloid-leukemia
#13
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...
November 4, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28802907/the-who-how-and-why-allogeneic-transplant-for-acute-myeloid-leukemia-in-patients-older-than-60years
#14
REVIEW
Sarah A Wall, Steven Devine, Sumithira Vasu
Acute myelogenous leukemia (AML) is primarily a disease of the elderly, and as such, our approach to treatment needs to be tailored to address an aging population. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative treatment for intermediate and high risk AML, and until recently, its use had been limited to a younger population and dependent on availability of a donor. Advances in conditioning regimens, supportive care, and the use of alternative donor sources have greatly expanded access to this therapy...
November 2017: Blood Reviews
https://www.readbyqxmd.com/read/28802906/pathways-towards-indolent-b-cell-lymphoma-etiology-and-therapeutic-strategies
#15
REVIEW
Michiel van den Brand, Blanca Scheijen, Corine J Hess, J Han Jm van Krieken, Patricia J T A Groenen
Although patients with indolent B-cell lymphomas have a relatively good survival rate, conventional chemotherapy is not curative. Disease courses are typically characterized by multiple relapses and progressively shorter response duration with subsequent lines of therapy. There has been an explosion of innovative targeted agents in the past years. This review discusses current knowledge on the etiology of indolent B-cell lymphomas with respect to the role of micro-organisms, auto-immune diseases, and deregulated pathways caused by mutations...
November 2017: Blood Reviews
https://www.readbyqxmd.com/read/28797519/treatment-of-acute-myeloid-leukemia-in-the-next-decade-towards-real-time-functional-testing-and-personalized-medicine
#16
REVIEW
Stephen Sze-Yuen Lam, Alex Bai-Liang He, Anskar Yu-Hung Leung
Information arising from next generation sequencing of leukemia genome has shed important light on the heterogeneous and combinatorial driver events in acute myeloid leukemia (AML). It has also provided insight into its intricate signaling pathways operative in the disease pathogenesis. These have also become biomarkers and targets for therapeutic intervention. Emerging evidence from in vitro drug screening has demonstrated its potential value in predicting clinical drug responses in specific AML subtypes. However, the best culture conditions and readouts have yet to be standardized and the drugs included in these screening exercises frequently revised in view of the rapid emergence of new therapeutic agents in the oncology field...
November 2017: Blood Reviews
https://www.readbyqxmd.com/read/28784423/diagnosis-and-management-of-the-antiphospholipid-syndrome
#17
REVIEW
Shruti Chaturvedi, Keith R McCrae
Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy complications in the presence of persistent antiphospholipid antibodies (APLA). Laboratory diagnosis of APLA depends upon the detection of a lupus anticoagulant, which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin (aCL) and anti-β2-glycoprotein-1 (β2GPI) antibodies. APLA are primarily directed toward phospholipid binding proteins. Pathophysiologic mechanisms underlying thrombosis and pregnancy loss in APS include APLA induced cellular activation, inhibition of natural anticoagulant and fibrinolytic systems, and complement activation, among others...
November 2017: Blood Reviews
https://www.readbyqxmd.com/read/28756877/platelet-populations-and-priming-in-hematological-diseases
#18
REVIEW
Constance C F M J Baaten, Hugo Ten Cate, Paola E J van der Meijden, Johan W M Heemskerk
In healthy subjects and patients with hematological diseases, platelet populations can be distinguished with different response spectra in hemostatic and vascular processes. These populations partly overlap, and are less distinct than those of leukocytes. The platelet heterogeneity is linked to structural properties, and is enforced by inequalities in the environment. Contributing factors are variability between megakaryocytes, platelet ageing, and positive or negative priming of platelets during their time in circulation...
November 2017: Blood Reviews
https://www.readbyqxmd.com/read/28755795/therapeutic-use-of-transferrin-to-modulate-anemia-and-conditions-of-iron-toxicity
#19
REVIEW
M Boshuizen, K van der Ploeg, L von Bonsdorff, B J Biemond, S S Zeerleder, R van Bruggen, N P Juffermans
As the main iron transporter, transferrin delivers iron to target tissues like the bone marrow for erythropoiesis. Also, by binding free iron, transferrin prevents formation of reactive oxygen species. Transferrin deficiency due to congenital hypotransferrinemia is characterized by anemia as well as oxidative stress related to toxic free iron. Transferrin supplementation may be beneficial in two ways. First, transferrin can correct anemia by modulating the amount of iron that is available for erythropoiesis...
November 2017: Blood Reviews
https://www.readbyqxmd.com/read/28732587/the-skin-as-a-window-to-the-blood-cutaneous-manifestations-of-myeloid-malignancies
#20
REVIEW
Alvin W Li, Emily S Yin, Maximilian Stahl, Tae Kon Kim, Gauri Panse, Amer M Zeidan, Jonathan S Leventhal
Cutaneous manifestations of myeloid malignancies are common and have a broad range of presentations. These skin findings are classified as specific, due to direct infiltration by malignant hematopoietic cells, or non-specific. Early recognition and diagnosis can have significant clinical implications, as skin manifestations may be the first indication of underlying hematologic malignancy, can reflect the immune status and stage of disease, and cutaneous reactions may occur from conventional and targeted agents used to treat myeloid disease...
November 2017: Blood Reviews
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