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Blood Reviews

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https://www.readbyqxmd.com/read/29728319/current-status-and-trends-in-the-diagnostics-of-aml-and-mds
#1
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/29709246/infections-in-patients-with-chronic-lymphocytic-leukaemia-mitigating-risk-in-the-era-of-targeted-therapies
#2
REVIEW
Benjamin W Teh, Constantine S Tam, Sasanka Handunnetti, Leon J Worth, Monica A Slavin
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection...
April 23, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29691090/myeloid-derived-suppressor-cells-in-lymphoma-the-good-the-bad-and-the-ugly
#3
REVIEW
A Betsch, O Rutgeerts, S Fevery, B Sprangers, G Verhoef, D Dierickx, M Beckers
Lymphomas cause significant morbidity and mortality worldwide. A substantial number of patients ultimately relapse after standard treatment. However, the efficacy of these therapies can be counteracted by the patients' immune system, more specifically by myeloid-derived suppressor cells (MDSC). MDSC are a heterogeneous group of immature myeloid cells that suppress the innate and adaptive immune system via different mechanisms and accumulate under pathological conditions, such as cancer. MDSC play a role in the induction and progression of cancer and immune evasion...
April 19, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29709247/blocking-don-t-eat-me-signal-of-cd47-sirp%C3%AE-in-hematological-malignancies-an-in-depth-review
#4
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...
April 14, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29699840/iron-toxicity-its-effect-on-the-bone-marrow
#5
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...
April 13, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29703513/t-cell-acute-lymphoblastic-leukemia-from-mirna-perspective-basic-concepts-experimental-approaches-and-potential-biomarkers
#6
REVIEW
Monika Drobna, Bronisława Szarzyńska-Zawadzka, Małgorzata Dawidowska
T-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive and heterogeneous malignancy originating from T-cell precursors. The mechanisms of T-ALL pathogenesis related to non-protein coding part of the genome are currently intensively studied. miRNAs are short, non-coding molecules acting as negative regulators of gene expression which shape phenotype of cells in a complex and context-specific manner. miRNAs may act as oncogenes or tumor suppressors; several miRNAs have been related to drug resistance and treatment response in various malignancies...
April 12, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29678553/recipient-and-donor-cells-in-the-graft-versus-solid-tumor-effect-it-takes-two-to-tango
#7
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...
April 12, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29627078/the-roles-of-jak2-in-dna-damage-and-repair-in-the-myeloproliferative-neoplasms-opportunities-for-targeted-therapy
#8
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...
March 30, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29706486/time-to-repeal-and-replace-response-criteria-for-acute-myeloid-leukemia
#9
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...
March 27, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29605154/prognostication-of-diffuse-large-b-cell-lymphoma-in-the-molecular-era-moving-beyond-the-ipi
#10
REVIEW
Joel C Wight, Geoffrey Chong, Andrew P Grigg, Eliza A Hawkes
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. Despite the majority of patients being cured with combination chemoimmunotherapy, up to 30% eventually succumb to the disease. Until recently, baseline prognostic assessment has centred on the International Prognostic Index (IPI), although this index is yet to impact strongly on treatment choice. Molecular features such as cell of origin, MYC and BCL-2 genetic alterations and protein overexpression were identified over a decade ago, yet their prognostic value is still not fully elucidated...
March 26, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29571669/chronic-lymphocytic-leukemia-and-infection-risk-in-the-era-of-targeted-therapies-linking-mechanisms-with-infections
#11
REVIEW
Talal Hilal, Juan C Gea Banacloche, Jose F Leis
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the world. Patient with CLL are at particular risk for infections due to inherent disease-related immune dysfunction in addition to the effect of certain systemic therapies on the immune system. The advent of B-cell receptor (BCR) inhibitors such as ibrutinib and idelalisib has led to a practice change that utilizes these targeted agents in the treatment of CLL, either in place of chemoimmunotherapy (CIT) or in later line settings. In this paper, we review the pathophysiology of immune dysfunction in CLL, the spectrum of immunodeficiency with the various therapeutic agents along with prevention strategies with a focus on targeted therapies...
March 16, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29551465/the-possible-role-of-maintenance-treatment-for-primary-central-nervous-system-lymphoma
#12
REVIEW
Osnat Bairey, Tali Siegal
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive brain tumor. The prognosis is poor, with high rates of relapse and disease progression after treatment. In addition, PCNSL affects a largely older population, so that a significant proportion of patients are ineligible for intensive therapies and high-dose chemotherapy. The elderly patients are also susceptible to the accelerated and detrimental cognitive side effects of whole-brain irradiation which is an alternative consolidation to high-dose chemotherapy...
March 11, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29602612/to-chelate-or-not-to-chelate-in-mds-that-is-the-question
#13
REVIEW
Amer M Zeidan, Elizabeth A Griffiths
Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopathies that exhibit physical manifestations with clinical consequences of bone marrow failure and inherent risk of progression to acute myeloid leukemia. Iron overload (IO) is common in MDS due to chronic transfusion support and disease-related alterations in iron metabolism. IO has been conclusively associated with inferior outcomes among MDS patients. Despite lack of randomized trials showing a survival impact of iron chelation therapy (ICT), ICT is recommended by experts and guidelines for select MDS patients with IO and is often used...
March 8, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29555368/approach-to-pancytopenia-diagnostic-algorithm-for-clinical-hematologists
#14
REVIEW
Jerome Gnanaraj, Aric Parnes, Charles W Francis, Ronald S Go, Clifford M Takemoto, Shahrukh K Hashmi
Pancytopenia is a relatively common phenomenon encountered in clinical practice. The evaluation of a patient with pancytopenia requires a comprehensive approach and identifying the underlying cause can be challenging given the wide range of etiologies including drugs, autoimmune conditions, malignancies, infections, hemophagocytosis, and inheritable conditions. Recent advances in molecular hematology which include genomic profiling and next-generation sequencing have helped gain major insights into various hematological conditions and can guide diagnosing specific diseases in a shorter time at lower costs...
March 5, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29126566/venous-thromboembolic-events-in-lymphoma-patients-actual-relationships-between-epidemiology-mechanisms-clinical-profile-and-treatment
#15
REVIEW
Darko Antic, Jelena Jelicic, Vojin Vukovic, Srdjan Nikolovski, Biljana Mihaljevic
Venous thromboembolic events (VTE) are an underestimated health problem in patients with lymphoma. Many factors contribute to the pathogenesis of thromboembolism and the interplay between various mechanisms that provoke VTE is still poorly understood. The identification of parameters that are associated with an increased risk of VTE in lymphoma patients led to the creation of several risk-assessment models. The models that evaluate potential VTE risk in lymphoma patients in particular are quite limited, and have to be validated in larger study populations...
March 2018: Blood Reviews
https://www.readbyqxmd.com/read/29122300/using-prognostic-models-in-cll-to-personalize-approach-to-clinical-care-are-we-there-yet
#16
REVIEW
Alain Mina, Jose Sandoval Sus, Elsa Sleiman, Javier Pinilla-Ibarz, Farrukh T Awan, Mohamed A Kharfan-Dabaja
Four decades ago, two staging systems were developed to help stratify CLL into different prognostic categories. These systems, the Rai and the Binet staging, depended entirely on abnormal exam findings and evidence of anemia and thrombocytopenia. Better understanding of biologic, genetic, and molecular characteristics of CLL have contributed to better appreciating its clinical heterogeneity. New prognostic models, the GCLLSG prognostic index and the CLL-IPI, emerged. They incorporate biologic and genetic information related to CLL and are capable of predicting survival outcomes and cases anticipated to need therapy earlier in the disease course...
March 2018: Blood Reviews
https://www.readbyqxmd.com/read/29033137/the-global-problem-of-early-deaths-in-acute-promyelocytic-leukemia-a-strategy-to-decrease-induction-mortality-in-the-most-curable-leukemia
#17
REVIEW
A P Jillella, V K Kota
Acute promyelocytic leukemia (APL) is a hyper-acute illness and presents with profound cytopenias in most patients and disseminated intravascular coagulation (DIC). Excellent treatment options are now available with drugs such as all-trans retinoic acid (ATRA), arsenic trioxide (ATO), anthracyclines and cytarabine. The outcome in APL has improved tremendously in the last 50years due to better understanding of the disease, development of effective targeted agents and improvement in supportive care. Carefully selected groups of patients treated in large multi-center trials on a protocol and in experienced centers have shown survival rates in excess of 85%...
March 2018: Blood Reviews
https://www.readbyqxmd.com/read/28969872/closing-the-gap-novel-therapies-in-treating-acute-lymphoblastic-leukemia-in-adolescents-and-young-adults
#18
REVIEW
Brian D Friend, Gary J Schiller
Acute lymphoblastic leukemia (ALL) is one of the most common cancer diagnoses identified in adolescents and young adults (AYAs). Although most children with ALL are cured of their disease, AYAs have experienced much worse outcomes over time, with event-free survival ranging from 30 to 45%. This survival disparity is likely due to differences in tumor biology, treatment-related toxicities, and nonmedical issues. This review summarizes these differences as well as focusing on the various trials that have demonstrated superior outcomes with pediatric protocols in AYAs with ALL...
March 2018: Blood Reviews
https://www.readbyqxmd.com/read/28965757/erythroleukemia-historical-perspectives-and-recent-advances-in-diagnosis-and-management
#19
REVIEW
Prajwal Boddu, Christopher B Benton, Wei Wang, Gautam Borthakur, Joseph D Khoury, Naveen Pemmaraju
Acute erythroleukemia is a rare form of acute myeloid leukemia recognized by its distinct phenotypic attribute of erythroblastic proliferation. After a century of its descriptive history, many diagnostic, prognostic, and therapeutic implications relating to this unique leukemia subset remain uncertain. The rarity of the disease and the simultaneous involvement of its associated myeloid compartment have complicated in vitro studies of human erythroleukemia cell lines. Although murine and cell line erythroleukemia models have provided valuable insights into pathophysiology, translation of these concepts into treatment are not forthcoming...
March 2018: Blood Reviews
https://www.readbyqxmd.com/read/28943040/treatment-of-musculo-skeletal-pain-in-haemophilia
#20
REVIEW
E Carlos Rodriguez-Merchan
Musculo-skeletal pain treatment is inadequate in many haemophilic patients. Analgesics are used only by 36% of adult patients. FVIII/FIX intravenous infusion is mainly used to lessen pain, followed in frequency by usage of NSAIDS (primarily COX-2 inhibitors). In about 30% of patients, pain continues after infusion of F VIII/IX. In acute haemarthroses pain treatment must continue until total disappearance (checked by ultrasonography) and include haematologic treatment, short-term rest of the involved joint, cryotherapy, joint aspiration and analgesic medication (paracetamol in mild pain, metamizole for more intense pain, and in a few precise patients, soft opioids such as codeine or tramadol)...
March 2018: Blood Reviews
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