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Blood Reviews

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https://read.qxmd.com/read/30711308/genetically-engineered-pigs-as-sources-for-clinical-red-blood-cell-transfusion-what-pathobiological-barriers-need-to-be-overcome
#1
REVIEW
Benjamin Smood, Hidetaka Hara, Leah J Schoel, David K C Cooper
An alternative to human red blood cells (RBCs) for clinical transfusion would be advantageous, particularly in situations of massive acute blood loss (where availability and compatibility are limited) or chronic hematologic diseases requiring frequent transfusions (resulting in alloimmunization). Ideally, any alternative must be neither immunogenic nor pathogenic, but readily available, inexpensive, and physiologically effective. Pig RBCs (pRBCs) provide a promising alternative due to their several similarities with human RBCs, and our increasing ability to genetically-modify pigs to reduce cellular immunogenicity...
January 28, 2019: Blood Reviews
https://read.qxmd.com/read/30704767/radiosynovectomy-in-haemophilia
#2
REVIEW
E Carlos Rodriguez-Merchan
Radiosynovectomy (RS) is a simple, effective and safe procedure for the control of haemophilic synovitis that causes repetitive haemarthrosis. It must be done after confirming clinically (hard and painless mass on palpation) and by ultrasonography the existence of synovitis in a joint with recurrent haemarthrosis. RS should be the first invasive option (instead of arthroscopic synovectomy) for treatment of chronic synovitis. The technique is highly cost effective in comparison to arthroscopic synovectomy. The indication for RS is the presence of repeated haemarthroses associated with synovitis (confirmed clinically and by imaging techniques) that cannot be controlled by means of haematological treatment...
January 25, 2019: Blood Reviews
https://read.qxmd.com/read/30683446/management-of-infectious-complications-in-multiple-myeloma-patients-expert-panel-consensus-based-recommendations
#3
REVIEW
Corrado Girmenia, Michele Cavo, Massimo Offidani, Francesco Scaglione, Alessandro Corso, Francesco Di Raimondo, Pellegrino Musto, Maria Teresa Petrucci, Giovanni Barosi
The introduction of new therapeutic agents in multiple myeloma (MM), including proteasome inhibitors, immunoregulatory drugs and monoclonal antibodies, has improved the outcomes of patients, but in parallel has changed the frequency and epidemiology of infections. Hence, the great strides in the indications and use of new active treatments for MM need parallel progresses on the best approach to prophylaxis and supportive therapy for infections. Moving from the recognition that the above issue represents an unmet clinical need in MM, an expert panel assessed the scientific literature and composed a framework of recommendations for optimal infection control in patients candidate to active treatment for MM...
January 9, 2019: Blood Reviews
https://read.qxmd.com/read/30553527/immunotherapy-in-acute-myeloid-leukemia-and-myelodysplastic-syndromes-the-dawn-of-a-new-era
#4
REVIEW
Yuxin Liu, Jan Philipp Bewersdorf, Maximilian Stahl, Amer M Zeidan
Immunotherapy has revolutionized therapy in both solid and liquid malignancies. The ability to cure acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an allogeneic hematopoietic stem cell transplant (HSCT) is proof of concept for the application of immunotherapy in AML and MDS. However, outside of HSCT, only the anti-CD33 antibody drug conjugate gemtuzumab ozogamicin is currently approved as an antibody-targeted therapy for AML. Several avenues of immunotherapeutic drugs are currently in different stages of clinical development...
December 5, 2018: Blood Reviews
https://read.qxmd.com/read/30616747/modelling-human-haemoglobin-switching
#5
REVIEW
Sarah T Diepstraten, Adam H Hart
Genetic lesions of the β-globin gene result in haemoglobinopathies such as β-thalassemia and sickle cell disease. To discover and test new molecular medicines for β-haemoglobinopathies, cell-based and animal models are now being widely utilised. However, multiple in vitro and in vivo models are required due to the complex structure and regulatory mechanisms of the human globin gene locus, subtle species-specific differences in blood cell development, and the influence of epigenetic factors. Advances in genome sequencing, gene editing, and precision medicine have enabled the first generation of molecular therapies aimed at reactivating, repairing, or replacing silenced or damaged globin genes...
January 2019: Blood Reviews
https://read.qxmd.com/read/30041977/are-low-molecular-weight-heparins-safe-and-effective-in-children-a-systematic-review
#6
REVIEW
Irene L M Klaassen, Jeanine J Sol, Monique H Suijker, K Fijnvandraat, Marianne D van de Wetering, C Heleen van Ommen
The incidence of venous thromboembolism (VTE) in children is rising. Hence, there is an increasing off-label use of low-molecular-weight heparin (LMWH). There is little data about therapeutic and prophylactic LWMH dosages, and their safety and efficacy. This systematic review provided an oversight of the therapeutic and prophylactic dosages of LMWH required to reach therapeutic and prophylactic target ranges. Furthermore, the safety and efficacy of LMWH, in terms of bleeding complications, achieving therapeutic and prophylactic anti-factor Xa levels, development of (recurrent) VTE and cloth resolution were reviewed...
January 2019: Blood Reviews
https://read.qxmd.com/read/30501907/the-impact-of-nf-%C3%AE%C2%BAb-signaling-on-pathogenesis-and-current-treatment-strategies-in-multiple-myeloma
#7
REVIEW
Dávid Vrábel, Luděk Pour, Sabina Ševčíková
Multiple myeloma, which ranks as the second most common hematological malignancy, is known for its great genetic heterogeneity. One pathway, however, stands out in this diverse group. NF-κB pathway is one of the most important pathways in multiple myeloma not only for its role in pathogenesis, but also for its importance in various treatment strategies. Mutations in several major components of the NF-κB pathway and its regulators are present in at least 17% of primary multiple myeloma tumors and 42% of multiple myeloma cell lines...
November 23, 2018: Blood Reviews
https://read.qxmd.com/read/30528964/recent-advances-in-car-t-cell-toxicity-mechanisms-manifestations-and-management
#8
REVIEW
Jennifer N Brudno, James N Kochenderfer
Chimeric antigen receptor (CAR) T-cell therapy is an effective new treatment for hematologic malignancies. Two CAR T-cell products are now approved for clinical use by the U.S. FDA: tisagenlecleucel for pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma subtypes (DLBCL), and axicabtagene ciloleucel for DLBCL. CAR T-cell therapies are being developed for multiple myeloma, and clear evidence of clinical activity has been generated. A barrier to widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) and neurologic toxicity...
November 14, 2018: Blood Reviews
https://read.qxmd.com/read/30467067/allogeneic-hematopoietic-cell-transplantation-the-current-renaissance
#9
REVIEW
Edward A Copelan, Aleksander Chojecki, Hillard M Lazarus, Belinda R Avalos
Allogeneic hematopoietic cell transplantation (HCT) provides the best chance for cure for many patients with malignant and nonmalignant hematologic disorders. Recent advances in selecting candidates and determining risk, procedure safety, utilization in older patients, use of alternative donors, and new or novel application of anti-cancer, immunosuppressive and antimicrobial agents have improved outcomes and expanded the role of HCT in hematologic disorders. Relapse remains the predominant cause of failure but enlightened use of new targeted and immunotherapeutic agents in combination with HCT promises to reduce relapse and further improve HCT outcomes...
November 8, 2018: Blood Reviews
https://read.qxmd.com/read/30401586/prognostic-and-therapeutic-role-of-clec12a-in-acute-myeloid-leukemia
#10
REVIEW
Linde M Morsink, Roland B Walter, Gert J Ossenkoppele
CLEC12A has recently been identified as an antigen, expressed on leukemic stem cells and leukemic blasts. Given the fact that this expression profile seems stable throughout diagnosis, treatment and relapse on leukemic blasts and leukemic stem cells, CLEC12A can be considered a highly potent and reliable marker for the detection of measurable residual disease and therefore applicable for risk stratification and prognostication in AML. Low CLEC12A expression on leukemic blasts seems to be independently associated with lower likelihood of achieving complete remission after 1 cycle of induction chemotherapy, shorter event free survival, as well as overall survival, indicating potential prognostic properties of CLEC12A expression itself...
November 1, 2018: Blood Reviews
https://read.qxmd.com/read/30075986/plasma-contact-factors-as-therapeutic-targets
#11
REVIEW
Benjamin F Tillman, Andras Gruber, Owen J T McCarty, David Gailani
Direct oral anticoagulants (DOACs) are small molecule inhibitors of the coagulation proteases thrombin and factor Xa that demonstrate comparable efficacy to warfarin for several common indications, while causing less serious bleeding. However, because their targets are required for the normal host-response to bleeding (hemostasis), DOACs are associated with therapy-induced bleeding that limits their use in certain patient populations and clinical situations. The plasma contact factors (factor XII, factor XI, and prekallikrein) initiate blood coagulation in the activated partial thromboplastin time assay...
November 2018: Blood Reviews
https://read.qxmd.com/read/29728319/current-status-and-trends-in-the-diagnostics-of-aml-and-mds
#12
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...
November 2018: Blood Reviews
https://read.qxmd.com/read/29709247/blocking-don-t-eat-me-signal-of-cd47-sirp%C3%AE-in-hematological-malignancies-an-in-depth-review
#13
REVIEW
Atlantis Russ, Anh B Hua, William R Montfort, Bushra Rahman, Irbaz Bin Riaz, Muhammad Umar Khalid, Jennifer S Carew, Steffan T Nawrocki, Daniel Persky, Faiz Anwer
Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148...
November 2018: Blood Reviews
https://read.qxmd.com/read/29699840/iron-toxicity-its-effect-on-the-bone-marrow
#14
REVIEW
Alessandro Isidori, Lorenza Borin, Elena Elli, Roberto Latagliata, Bruno Martino, Giuseppe Palumbo, Federica Pilo, Federica Loscocco, Giuseppe Visani, Paolo Cianciulli
Excess iron can be extremely toxic for the body and may cause organ damage in the absence of iron chelation therapy. Preclinical studies on the role of free iron on bone marrow function have shown that iron toxicity leads to the accumulation of reactive oxygen species, affects the expression of genes coding for proteins that regulate hematopoiesis, and disrupts hematopoiesis. These effects could be partially attenuated by iron-chelation treatment with deferasirox, suggesting iron toxicity may have a negative impact on the hematopoietic microenvironment...
November 2018: Blood Reviews
https://read.qxmd.com/read/29678553/recipient-and-donor-cells-in-the-graft-versus-solid-tumor-effect-it-takes-two-to-tango
#15
REVIEW
Isabelle Dierckx de Casterlé, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation (alloHSCT) produces -similar to the long-established graft-versus-leukemia effect- graft-versus-solid-tumor effects. Clinical trials reported response rates of up to 53%, occurring mostly but not invariably in association with full donor chimerism and/or graft-versus-host disease. Although donor-derived T cells are considered the principal effectors of anti-tumor immunity after alloHSCT or donor leukocyte infusion (DLI), growing evidence indicate that recipient-derived immune cells may also contribute...
November 2018: Blood Reviews
https://read.qxmd.com/read/30448050/infection-control-in-patients-with-myelodysplastic-syndromes-who-are-candidates-for-active-treatment-expert-panel-consensus-based-recommendations
#16
REVIEW
Corrado Girmenia, Anna Candoni, Mario Delia, Roberto Latagliata, Alfredo Molteni, Esther N Oliva, Giuseppe A Palumbo, Antonella Poloni, Prassede Salutari, Valeria Santini, Maria Teresa Voso, Pellegrino Musto
The improvement in supportive care and the introduction of new therapeutic agents, including lenalidomide and hypomethylating agents, in myelodysplastic syndromes have improved patients' outcomes; however, at the same time, the frequency and epidemiology of infections have changed. Therefore, the great strides in the indications and use of new treatment strategies for myelodysplastic syndromes need a parallel progress in the best approach to prophylaxis and supportive therapy for infections. Based on the recognition that the above issues represent an unmet clinical need in myelodysplastic syndromes, an Italian expert panel performed a review of the literature and composed a framework of the best recommendations for optimal infection control in patient candidates to receive active treatment for myelodysplastic syndromes...
October 28, 2018: Blood Reviews
https://read.qxmd.com/read/30318111/temporary-removal-are-thrombocytopenia-and-platelet-transfusions-associated-with-major-bleeding-in-preterm-neonates-a-systematic-review
#17
S F Fustolo-Gunnink, E J Huijssen-Huisman, J G van der Bom, F M A van Hout, S Makineli, E Lopriore, K Fijnvandraat
No abstract text is available yet for this article.
October 9, 2018: Blood Reviews
https://read.qxmd.com/read/30314642/epidemiology-of-myelodysplastic-syndromes-why-characterizing-the-beast-is-a-prerequisite-to-taming-it
#18
REVIEW
Amer M Zeidan, Rory M Shallis, Rong Wang, Amy Davidoff, Xiaomei Ma
Myelodysplastic syndromes (MDS) consist of a heterogeneous group of myeloid neoplasms characterized by inefficient hematopoiesis, variable cytopenias and a considerable risk of progression to acute myeloid leukemia. Epidemiological assessment of MDS has been hampered by evolving diagnostic criteria and delayed classification of MDS as cancers until 2001. The poorly-understood nature of these neoplasms combined with the lack of effective therapies for decades contributed to suboptimal case ascertainment and underreporting...
September 21, 2018: Blood Reviews
https://read.qxmd.com/read/29706486/time-to-repeal-and-replace-response-criteria-for-acute-myeloid-leukemia
#19
REVIEW
Clara Derber Bloomfield, Elihu Estey, Lisa Pleyer, Andre C Schuh, Eytan M Stein, Martin S Tallman, Andrew Wei
The International Working Group (IWG) response criteria for acute myeloid leukemia, published in 2003, have remained the standard by which the efficacy of new drugs is measured in clinical trials. Over the last decade, concepts related to treatment response have been challenged by several factors; for example, the dissociation between early clinical response and survival outcome in older patients, the recognition that epigenetic and newer differentiating-agent therapies may produce delayed responses and also hematologic improvement/transfusion independence without a morphologic response, and evidence that remissions without minimal (or measurable) residual disease (MRD) may result in outcomes superior to those of morphologic remissions with persistent MRD...
September 2018: Blood Reviews
https://read.qxmd.com/read/29627078/the-roles-of-jak2-in-dna-damage-and-repair-in-the-myeloproliferative-neoplasms-opportunities-for-targeted-therapy
#20
REVIEW
Theodoros Karantanos, Alison R Moliterno
The JAK2V617F-positive myeloproliferative neoplasms (MPN) serve as an excellent model for the study of genomic instability accumulation during cancer progression. Recent studies highlight the implication of JAK2 activating mutations in the development of DNA damage via reactive oxygen species (ROS) production, replication stress induction and the accumulation of genomic instability via the increased degradation of p53 and acquisition of a "mutagenic" phenotype. The accumulation of genomic instability and acquisition of mutations in critical DNA damage repair (DDR) mediators appears to be implicated in the progression of JAK2V617F-positive MPN...
September 2018: Blood Reviews
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