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Blood Reviews

Alessandro Di Minno, Gaia Spadarella, Antonio Nardone, Mauro Mormile, Itala Ventre, Massimo Morfini, Giovanni Di Minno
Haemophilia is marked by joint bleeding (haemarthrosis) leading to cartilage damage (arthropathy). Lifelong prophylaxis-initiated after the first bleeding episode-leads to a dramatic decrease in arthropathy in haemophilia patients. However, adherence to continuous intravenous administrations of factor VIII (FVIII) or FIX products is challenging, and patients potentially suffer from breakthrough bleedings while on prophylaxis. Newer FVIII/FIX products with enhanced convenience attributes and/or easier infusion procedures are intended to improve adherence...
August 20, 2018: Blood Reviews
Elisa Quiroz, Ibrahim Aldoss, Vinod Pullarkat, Eduardo Rego, Guido Marcucci, Dan Douer
Higher incidence rates and poor outcomes have been reported among Latin American patients (Latinos) with acute lymphoblastic leukemia (ALL). Distinct patterns in recent genomic studies allude to a predisposing genetic component. In this review, we critically examine the increasing amount of empirical information on the epidemiology, outcomes and genomics of Latinos with ALL. We discuss the immense diversity within the Latino community and varying definitions of what is considered Latino, which pose an epidemiological challenge...
August 14, 2018: Blood Reviews
Luuk J J Scheres, Ingrid M Bistervels, Saskia Middeldorp
Pregnancy is a hemostatic challenge: women are prone to thromboembolism during their pregnancy and at the same time, especially during delivery, there is substantial risk of bleeding. Pregnant women are often excluded from randomized controlled trials, and high quality evidence regarding optimal anticoagulant management is thus lacking. Anticoagulants are being used in pregnancy for prevention and treatment of various pregnancy complications such as thrombotic events, preeclampsia and pregnancy loss. When anticoagulant therapy is necessary, special attention should be given to both woman and unborn child...
August 6, 2018: Blood Reviews
Lauren C Schwartz, John Mascarenhas
Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1 negative myelodysplastic (MDS)/myeloproliferative (MPN) neoplasm with poor overall survival. The current 2016 WHO classification of myeloid neoplasms allows clinicians to more accurately differentiate aCML from its similar MDS/MPN overlap and MPN counterparts. In addition, the advent of next-generation sequencing has expanded our understanding of the molecular pathogenesis of aCML and its therapeutic potential. Hematopoietic stem cell transplant (HSCT) remains the first consideration in the treatment algorithm for aCML, however, with the advances in mutational analysis, opportunities for targeted therapy have expanded...
July 29, 2018: Blood Reviews
Moussab Damlaj, Riad El Fakih, Shahrukh K Hashmi
Recent advancements in cancer care, coupled with early detection and an aging population have resulted in significant growth of cancer survivors. Long term follow up of such survivors is essential given the heightened risk for development of late effects such as secondary neoplasms, cardiovascular disease or psychosocial dysfunction among others. As more patients with hematologic malignancies are cured or managed over protracted periods of time, awareness of such issues is paramount for the practicing clinicians for optimal patient management...
July 25, 2018: Blood Reviews
Abraham Degarege, Merhawi T Gebrezgi, Gladys Ibanez, Mats Wahlgren, Purnima Madhivanan
Understanding how ABO blood group interacts with Plasmodium falciparum (P. falciparum) infection may facilitate development of antimalarial treatments and vaccines. This study systematically summarizes information on the relationship of ABO blood group with severe P. falciparum infection, level of parasitemia and haemoglobin. A total of 1923 articles were retrieved from five databases. After removal of duplicates, and two levels of screening, 21 articles were selected for inclusion in the meta-analysis. A meta-analysis of the studies showed an increased odds of severe P...
July 17, 2018: Blood Reviews
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
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...
June 28, 2018: Blood Reviews
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
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
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...
September 2018: Blood Reviews
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...
September 2018: Blood Reviews
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...
September 2018: Blood Reviews
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...
September 2018: Blood Reviews
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...
September 2018: Blood Reviews
Erin J Howden, André La Gerche, Jane F Arthur, Julie R McMullen, Garry L Jennings, David W Dunstan, Neville Owen, Sharon Avery, Bronwyn A Kingwell
Hematological cancer survivors are highly vulnerable to cardiometabolic complications impacting long-term health status, quality of life and survival. Elevated risk of diabetes and cardiovascular disease arises not only from the effects of the cancers themselves, but also from the toxic effects of cancer therapies, and deconditioning arising from reduced physical activity levels. Regular physical activity can circumvent or reverse adverse effects on the heart, skeletal muscle, vasculature and blood cells, through a combination of systemic and molecular mechanisms...
September 2018: Blood Reviews
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
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
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
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
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