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Expert Review of Hematology

Douglas Tremblay, John Mascarenhas
Treatment with ruxolitinib, a selective JAK1/2 inhibitor, has significantly improved the lives of patients with myelofibrosis. Unfortunately, this treatment is frequently limited by cytopenias, precluding a high-risk group characterized by baseline thrombocytopenia. Additionally, there are no approved treatments for patients who have progressed while receiving ruxolitinib. Pacritinib is a novel JAK2/FLT3 inhibitor associated with less treatment-related myelosuppression that has the potential to fill these unmet treatment needs...
July 12, 2018: Expert Review of Hematology
Marcel Levi, Suthesh Sivapalaratnam
Activation of the hemostatic system can occur in many clinical conditions. However, a systemic and strong activation of coagulation complicating clinical settings such as sepsis, trauma or malignant disease may result in the occurrence disseminated intravascular coagulation (DIC). Areas covered: This article reviews the clinical manifestation and relevance of DIC, the various conditions that may precipitate DIC and the pathogenetic pathways underlying the derangement of the hemostatic system, based on clinical and experimental studies...
July 12, 2018: Expert Review of Hematology
Shaoying Li, Pei Lin, L Jeffrey Medeiros
The designation high-grade B-cell lymphoma (HGBL) has been incorporated into the 2016 Revision of the WHO classification of lymphoid neoplasms and includes two types: (1) HGBL, not otherwise specified; and (2) HGBL with MYC and BCL2 and/or BCL6 rearrangements, also known as double or triple hit lymphoma (DHL/THL). These categories of lymphomas represent 1-2% of non-Hodgkin lymphomas and a considerable portion of DLBCL patients who are primary refractory to R-CHOP therapy. It corresponds to the designation 'B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma' in the 2008 WHO classification...
July 10, 2018: Expert Review of Hematology
Francesca R Mauro, Maria D Caputo, Serena Rosati, Sara Pepe, Daniela De Benedittis, Maria L De Luca, Robin Foà
In recent years, innovative mechanism-based drugs have enriched the therapeutic armamentarium for patients with chronic lymphocytic leukemia [CLL] and are widely used in the clinical practice. These small molecules targeting the B-cell receptor signaling pathway and the Bcl-2 anti-apoptotic protein offer new chemo-free options to both unfit patients and high-risk patients who show a poor response to chemoimmunotherapy. Nonetheless, treatment with ibrutinib, idelalisib and venetoclax is associated with unique side effects...
July 3, 2018: Expert Review of Hematology
Martina Crysandt, Kira Brings, Fabian Beier, Christian Thiede, Tim H Brümmendorf, Edgar Jost
Germline predisposition to myeloid neoplasms has been incorporated in the WHO 2016 classification of myeloid neoplasms and acute leukemia. The new category of disease is named hereditary myeloid disorder (HMD). Although most myeloid neoplasms are sporadic, germline mutations and familial predisposition can contribute to development of chronic myeloid diseases and acute myeloid leukemia. This finding and upcoming frequent use of genome wide detection of molecular aberrations will lead to a higher detection rate of a genetic predisposition and influence treatment decisions...
June 29, 2018: Expert Review of Hematology
Gareth J Morgan, Leo Rasche
Utilizing advances in genetic and immunologic analysis to segment and direct treatment is potentially a way of maintaining therapeutic progress toward cure in multiple myeloma (MM). This approach works well using clinical segments but can be optimized using recent genetic and immunologic technologies, which have opened the possibility of enhancing risk stratification and disease subclassification. Areas covered: This position paper discusses strategies to segment myeloma into subgroups with distinct risk profiles and distinct targetable lesions are presented...
June 26, 2018: Expert Review of Hematology
Tim R de Back, Arnon P Kater, Sanne H Tonino
Chronic lymphocytic leukemia (CLL) is frequently complicated by cytopenias, either due to bone marrow infiltration or autoimmunity, resulting in autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia (PRCA) or autoimmune neutropenia (AIN). Morbidity due to autoimmune cytopenias (AIC) can be substantial; in addition, infection risk increases and pre-existing infections might deteriorate due to immunosuppressive medication. In the aging population, CLL occurs more frequently and AIC related to CLL represent a growing clinical challenge...
June 20, 2018: Expert Review of Hematology
Jamile M Shammo, Rami S Komrokji
Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS...
June 19, 2018: Expert Review of Hematology
Giorgio Minotti, Haiyong Han, Valérie Cattan, Anton Egorov, Francesco Bertoni
Pixantrone is a first-in-class aza-anthracenedione approved as monotherapy for treatment of relapsed or refractory aggressive diffuse B-cell non-Hodgkin's lymphoma (NHL), a patient group which is notoriously difficult to treat. It has a unique chemical structure and pharmacologic properties distinguishing it from anthracyclines and anthracenediones. Areas covered: The chemical structure and mode of action of pixantrone versus doxorubicin and mitoxantrone; preclinical evidence for pixantrone's therapeutic effect and cardiac tolerability; efficacy and safety of pixantrone in clinical trials; ongoing and completed trials of pixantrone alone or as combination therapy; and the risk of cardiotoxicity of pixantrone versus doxorubicin and mitoxantrone...
June 18, 2018: Expert Review of Hematology
Giancarlo Castaman
The health benefits of prophylactic dosing regimens for clotting factor therapy in patients with hemophilia include reduced joint damage and improved quality of life and, as such, prophylaxis is recommended in treatment guidelines. However, many patients with hemophilia B are treated on demand, and prophylaxis has been utilized less frequently than in hemophilia A. Areas covered: This review discusses the opportunities and evidence for prophylaxis in hemophilia B, in the context of treatment guidelines and with regard to factor IX (FIX) replacement therapies, including long-acting recombinant FIX (rFIX)...
June 18, 2018: Expert Review of Hematology
Luciana Teofili, Antonietta R Silini, Maria Bianchi, Caterina Giovanna Valentini, Ornella Parolini
Human term placenta is comprised of various tissues from which different cell populations can be obtained, including hematopoietic stem cells and mesenchymal stem/stromal cells (MSCs). Areas covered: This review will discuss the possibility to incorporate placental tissue cells in cord blood banking. It will discuss general features of human placenta, with a brief review of the immune cells at the fetal-maternal interface and the different cell populations isolated from placenta, with a particular focus on MSCs...
June 1, 2018: Expert Review of Hematology
Giancarlo Castaman, Silvia Linari
Early long-term prophylaxis is the standard of care to prevent joint bleeding and chronic arthropathy in patients with severe hemophilia. Areas covered: Despite the obvious prophylaxis advantages upon the clinical outcomes, there are still several drawbacks to be addressed for the optimal patients' compliance. Frequency of treatment due to short half-life of conventional FVIII and FIX concentrates, difficult venous access, adherence to the prescribed therapy and costs may represent significant critical issues...
July 2018: Expert Review of Hematology
Alexis Leonard, John F Tisdale
Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide, and is a life-limiting disease with limited therapeutic options to reduce disease severity. Despite being a monogenic disorder, the clinical phenotypes of SCD are variable, with few reliable predictors of disease severity easily identifying patients where the benefits of curative therapy outweigh the risks. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option, though significant advances in gene therapy raise the promise for additional curative methods...
July 2018: Expert Review of Hematology
Elisa Rumi, Emanuela Sant'Antonio, Emanuela Boveri, Daniela Pietra, Chiara Cavalloni, Elisa Roncoroni, Cesare Astori, Luca Arcaini
The 2016 WHO classification comprises two stages of primary myelofibrosis (PMF): early/prefibrotic primary myelofibrosis (pre-PMF) and overt fibrotic PMF (overt PMF). Diagnostic criteria rely on bone marrow morphology, fibrosis grade (0-1 in pre-PMF, 2-3 in overt PMF), and clinical features (leukoerythroblastosis, anemia, leucocytosis, increased lactate dehydrogenase, and palpable splenomegaly). An accurate differentiation from essential thrombocythemia (ET) is pivotal because the two entities show different clinical presentation and outcome, in terms of survival, leukemic evolution, and rates of progression to overt myelofibrosis...
July 2018: Expert Review of Hematology
Jessica Liegel, David Avigan, Jacalyn Rosenblatt
Immunotherapy seeks to restore and augment the unique ability of the immune system to recognize and kill malignant cells. This strategy has previously been incorporated into standard of care in myeloma with the use of immunomodulatory drugs and allogeneic transplant. The following review will discuss the rationale for immunotherapy to reverse critical aspects of the immunosuppressive milieu in myeloma and avenues where cellular therapies are now revolutionizing myeloma treatment. Areas covered: A particular focus is outcomes of clinical trials in myeloma published in PubMed database or abstract form using vaccines or adoptive cell transfer: marrow infiltrating lymphocytes, T-cell receptor and chimeric antigen receptor T cells...
July 2018: Expert Review of Hematology
Giuseppe Visani, Federica Loscocco, Alessandro Isidori, Pier Paolo Piccaluga
Despite substantial progresses in acute myeloid leukemia (AML) diagnosis and treatment, at least half of patient will eventually die for the disease. In the last decades, the use of genetic and genomic approaches allowed the identification of patients with higher risk of recurrence after and/or resistance to CHT. However, though many novel drugs have been proposed and tested, only little clinical improvements have been made concerning the treatment of the so called 'high risk' patients. Areas covered: In this article, the authors, based on their own experience and the most updated literature, review the basic knowledge of AML prognostication and treatment prediction developed throughout genetic and genomic profiling, and focus on the use of gene expression profiling as a promising predictive tool...
June 2018: Expert Review of Hematology
Hikmat Abdel-Razeq, Antoine Finianos, Ali T Taher
After the CLOT study, LMWHs (low-molecular weight heparins) have gradually replaced warfarin as the treatment of choice for VTE (venous thromboembolism) in cancer patients. Randomized controlled studies comparing DOACs (direct oral anticoagulants) to LMWHs in cancer patients are still limited. However, new emerging data are supporting the use of DOACs in cancer-associated thrombosis. Areas covered: This review will discuss the recent studies that addressed the utilization of such agents in the treatment of VTE in cancer patients...
June 2018: Expert Review of Hematology
Stefano Molica
Novel targeted therapies - including ibrutinib, venetoclax, and idelalisib - have revolutionized the treatment landscape of chronic lymphocytic leukemia (CLL). Therefore, studying combinations of novel agents (NAs) with a distinct mechanism of action and nonoverlapping toxicities is challenging. Area covered: The 2017 American Society Hematology Annual Meeting has represented a showcase for several trials combining NAs. These studies are currently evaluating the efficacy NA plus anti-CD20 monoclonal antibody, NA plus NA (with or without anti-CD20 monoclonal antibody), and NA plus chemo-immunotherapy...
June 2018: Expert Review of Hematology
Magdalini Migkou, Maria Gavriatopoulou, Evangelos Terpos, Meletios Athanasios Dimopoulos
Multiple myeloma prognosis has improved significantly during the past decade, with survival prolongation mainly due to the incorporation of novel agents. Bortezomib represents one of the main backbone agents of antimyeloma treatment. Areas covered: This review aims to identify possible and available therapeutic options for patients who experience disease refractoriness following bortezomib exposure. Expert commentary: For patients who finally relapse after bortezomib exposure treatment strategy should be individualized...
June 2018: Expert Review of Hematology
Sam Keeping, Elise Wu, Keith Chan, Ali Mojebi, Shannon Allen Ferrante, Arun Balakumaran
BACKGROUND: There is significant unmet need among patients with relapsed and refractory classical Hodgkin's lymphoma (RRcHL) who have failed multiple lines of therapy, including brentuximab vedotin (BV). Pembrolizumab, an immune checkpoint inhibitor, is one possible treatment solution for this population. RESEARCH METHODS: The objective of this study was to compare progression-free survival (PFS) with standard of care (SOC) versus pembrolizumab in previously BV treated RRcHL patients...
June 2018: Expert Review of Hematology
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