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https://www.readbyqxmd.com/read/28644114/midostaurin-plus-chemotherapy-for-acute-myeloid-leukemia-with-a-flt3-mutation
#1
RANDOMIZED CONTROLLED TRIAL
Richard M Stone, Sumithra J Mandrekar, Ben L Sanford, Kristina Laumann, Susan Geyer, Clara D Bloomfield, Christian Thiede, Thomas W Prior, Konstanze Döhner, Guido Marcucci, Francesco Lo-Coco, Rebecca B Klisovic, Andrew Wei, Jorge Sierra, Miguel A Sanz, Joseph M Brandwein, Theo de Witte, Dietger Niederwieser, Frederick R Appelbaum, Bruno C Medeiros, Martin S Tallman, Jürgen Krauter, Richard F Schlenk, Arnold Ganser, Hubert Serve, Gerhard Ehninger, Sergio Amadori, Richard A Larson, Hartmut Döhner
BACKGROUND: Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin - an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation - to standard chemotherapy would prolong overall survival in this population. METHODS: We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo...
August 3, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28548080/discovery-of-first-in-class-reversible-dual-small-molecule-inhibitors-against-g9a-and-dnmts-in-hematological-malignancies
#2
Edurne San José-Enériz, Xabier Agirre, Obdulia Rabal, Amaia Vilas-Zornoza, Juan A Sanchez-Arias, Estibaliz Miranda, Ana Ugarte, Sergio Roa, Bruno Paiva, Ander Estella-Hermoso de Mendoza, Rosa María Alvarez, Noelia Casares, Victor Segura, José I Martín-Subero, François-Xavier Ogi, Pierre Soule, Clara M Santiveri, Ramón Campos-Olivas, Giancarlo Castellano, Maite Garcia Fernandez de Barrena, Juan Roberto Rodriguez-Madoz, Maria José García-Barchino, Juan Jose Lasarte, Matias A Avila, Jose Angel Martinez-Climent, Julen Oyarzabal, Felipe Prosper
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28297628/genetic-basis-of-acute-lymphoblastic-leukemia
#3
REVIEW
Ilaria Iacobucci, Charles G Mullighan
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and despite cure rates exceeding 90% in children, it remains an important cause of morbidity and mortality in children and adults. The past decade has been marked by extraordinary advances into the genetic basis of leukemogenesis and treatment responsiveness in ALL. Both B-cell and T-cell ALL comprise multiple subtypes harboring distinct constellations of somatic structural DNA rearrangements and sequence mutations that commonly perturb lymphoid development, cytokine receptors, kinase and Ras signaling, tumor suppression, and chromatin modification...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28297626/clinical-applications-of-the-genomic-landscape-of-aggressive-non-hodgkin-lymphoma
#4
REVIEW
Andrea B Moffitt, Sandeep S Dave
In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28153603/high-programmed-death-1-expression-on-t-cells-in-aplastic-anemia
#5
Wanhong Zhao, Yilin Zhang, Pengyu Zhang, Juan Yang, Longjin Zhang, Aili He, Wanggang Zhang, Tamura Hideto
Programmed death 1 (PD-1) has been reported to be associated with aberrant regulation of T cells activation in aplastic anemia (AA). However, the connection between PD-1 expression status and AA needs to be further explored. The aim of this study is to investigate PD-1 expression status on T cells in AA patients and to explore the effect of PD-1 on apoptosis of T cells and BMHSCs. The concentration of platelet, lymphocyte and hemoglobin in peripheral blood of AA patients and healthy volunteers was detected by automatic blood-counter system...
March 2017: Immunology Letters
https://www.readbyqxmd.com/read/28146266/how-i-manage-patients-with-hairy-cell-leukaemia
#6
REVIEW
Philip A Thompson, Farhad Ravandi
Patients with hairy cell leukaemia (HCL) have highly favourable outcomes after purine analogue therapy. However, most patients subsequently relapse and require re-treatment. A minority of patients develop purine analogue-refractory disease. Targeted therapies have improved outcomes for such patients. Recently, the BRAF V600E mutation was identified in most patients with classical HCL, resulting in constitutive mitogen-activated protein kinase pathway activation; impressive responses are achieved in heavily pre-treated patients with BRAF inhibition...
May 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27009448/single-cell-rna-sequencing-reveals-molecular-and-functional-platelet-bias-of-aged-haematopoietic-stem-cells
#7
Amit Grover, Alejandra Sanjuan-Pla, Supat Thongjuea, Joana Carrelha, Alice Giustacchini, Adriana Gambardella, Iain Macaulay, Elena Mancini, Tiago C Luis, Adam Mead, Sten Eirik W Jacobsen, Claus Nerlov
Aged haematopoietic stem cells (HSCs) generate more myeloid cells and fewer lymphoid cells compared with young HSCs, contributing to decreased adaptive immunity in aged individuals. However, it is not known how intrinsic changes to HSCs and shifts in the balance between biased HSC subsets each contribute to the altered lineage output. Here, by analysing HSC transcriptomes and HSC function at the single-cell level, we identify increased molecular platelet priming and functional platelet bias as the predominant age-dependent change to HSCs, including a significant increase in a previously unrecognized class of HSCs that exclusively produce platelets...
March 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27895058/diagnosis-and-management-of-aml-in-adults-2017-eln-recommendations-from-an-international-expert-panel
#8
REVIEW
Hartmut Döhner, Elihu Estey, David Grimwade, Sergio Amadori, Frederick R Appelbaum, Thomas Büchner, Hervé Dombret, Benjamin L Ebert, Pierre Fenaux, Richard A Larson, Ross L Levine, Francesco Lo-Coco, Tomoki Naoe, Dietger Niederwieser, Gert J Ossenkoppele, Miguel Sanz, Jorge Sierra, Martin S Tallman, Hwei-Fang Tien, Andrew H Wei, Bob Löwenberg, Clara D Bloomfield
The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations...
January 26, 2017: Blood
https://www.readbyqxmd.com/read/28096088/how-i-treat-acquired-aplastic-anemia
#9
REVIEW
Andrea Bacigalupo
Acquired severe aplastic anemia (SAA) is a rare hematologic disease associated with significant morbidity and mortality. Immune destruction of hemopoietic stem cells plays an important role in pathogenesis, as shown by successful treatment with immunosuppressive agents, leading to transfusion independence or complete recovery of peripheral blood counts in a proportion of patients. Growth factors can be combined with immunosuppressive therapy (IST) and may improve response rates, as recently shown with thrombopoietin analogs...
March 16, 2017: Blood
https://www.readbyqxmd.com/read/28094456/waldenstr%C3%A3-m-macroglobulinemia-2017-update-on-diagnosis-risk-stratification-and-management
#10
Morie A Gertz
Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. DIAGNOSIS: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients. Risk Stratification: Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis...
February 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/27799160/sensing-of-the-microbiota-by-nod1-in-mesenchymal-stromal-cells-regulates-murine-hematopoiesis
#11
Chiaki Iwamura, Nicolas Bouladoux, Yasmine Belkaid, Alan Sher, Dragana Jankovic
The microbiota is known to influence the generation of hematopoietic progenitors, although the pathways underlying this process are still poorly understood. NOD1 and NOD2 are intracellular sensors for both Gram-positive and Gram-negative bacteria, but their role in steady-state hematopoiesis has never been characterized. We observed that stimulation with NOD1 or NOD2 ligand had no effect on the survival/proliferation of hematopoietic precursors. Nonetheless, NOD1, but not NOD2, ligand induced expression of multiple hematopoietic cytokines (interleukin-7 [IL-7], Flt3L, stem cell factor [SCF], ThPO, and IL-6) from bone marrow mesenchymal stromal cells (MSCs) in vitro...
January 12, 2017: Blood
https://www.readbyqxmd.com/read/27731885/transfusion-thresholds-and-other-strategies-for-guiding-allogeneic-red-blood-cell-transfusion
#12
REVIEW
Jeffrey L Carson, Simon J Stanworth, Nareg Roubinian, Dean A Fergusson, Darrell Triulzi, Carolyn Doree, Paul C Hebert
BACKGROUND: There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients. OBJECTIVES: The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions...
October 12, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27489982/venous-thromboembolism-in-patients-with-hematologic-malignancy-and-thrombocytopenia
#13
Nabin Khanal, R Gregory Bociek, Baojiang Chen, Julie M Vose, James O Armitage, Philip J Bierman, Lori J Maness, Matthew A Lunning, Krishna Gundabolu, Vijaya R Bhatt
The optimal management of hematologic malignancy-associated venous thromboembolism (VTE) in patients with moderate-to-severe thrombocytopenia is unclear. This is a retrospective study of 128 adult patients with hematologic malignancies who were diagnosed with VTE. The outcome of patients with significant thrombocytopenia (≤50,000/µL) was compared with those without. Forty-seven patients (36.7%) had a platelet count ≤50,000/µL during a period of time of perceived need for new or continued anticoagulation...
November 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27445412/clonal-hematopoiesis-in-aa
#14
(no author information available yet)
No abstract text is available yet for this article.
July 21, 2016: Blood
https://www.readbyqxmd.com/read/27410923/ipilimumab-for-patients-with-relapse-after-allogeneic-transplantation
#15
MULTICENTER STUDY
Matthew S Davids, Haesook T Kim, Pavan Bachireddy, Caitlin Costello, Rebecca Liguori, Alexandra Savell, Alexander P Lukez, David Avigan, Yi-Bin Chen, Peter McSweeney, Nicole R LeBoeuf, Michael S Rooney, Michaela Bowden, Chensheng W Zhou, Scott R Granter, Jason L Hornick, Scott J Rodig, Masahiro Hirakawa, Mariano Severgnini, F Stephen Hodi, Catherine J Wu, Vincent T Ho, Corey Cutler, John Koreth, Edwin P Alyea, Joseph H Antin, Philippe Armand, Howard Streicher, Edward D Ball, Jerome Ritz, Asad Bashey, Robert J Soiffer
BACKGROUND: Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. METHODS: We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT...
July 14, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27367478/-acute-myeloid-leukemia-a-comprehensive-review-and-2016-update
#16
REVIEW
I De Kouchkovsky, M Abdul-Hay
Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with an incidence of over 20 000 cases per year in the United States alone. Large chromosomal translocations as well as mutations in the genes involved in hematopoietic proliferation and differentiation result in the accumulation of poorly differentiated myeloid cells. AML is a highly heterogeneous disease; although cases can be stratified into favorable, intermediate and adverse-risk groups based on their cytogenetic profile, prognosis within these categories varies widely...
July 1, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/26436602/comparison-of-a-restrictive-versus-liberal-red-cell-transfusion-policy-for-patients-with-myelodysplasia-aplastic-anaemia-and-other-congenital-bone-marrow-failure-disorders
#17
REVIEW
Yisu Gu, Lise J Estcourt, Carolyn Doree, Sally Hopewell, Paresh Vyas
BACKGROUND: Bone marrow failure disorders include a heterogenous group of disorders, of which myelodysplastic syndrome (MDS), forms the largest subgroup. MDS is predominantly a disease of the elderly, with many elderly people managed conservatively with regular allogeneic red blood cell (RBC) transfusions to treat their anaemia. However, RBC transfusions are not without risk. Despite regular transfusions playing a central role in treating such patients, the optimal RBC transfusion strategy (restrictive versus liberal) is currently unclear...
October 5, 2015: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27341755/the-2016-revision-of-who-classification-of-myeloproliferative-neoplasms-clinical-and-molecular-advances
#18
REVIEW
T Barbui, J Thiele, H Gisslinger, G Finazzi, A M Vannucchi, A Tefferi
Clinical evidence supports the need of changing the diagnostic criteria of the 2008 updated WHO classification for polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In JAK2-mutated patients who show characteristic bone marrow (BM) morphology, clinical studies demonstrated that a hemoglobin level of 16.5g/dL in men and 16.0g/dl for women or a hematocrit value of 49% in men and 48% in women are the optimal cut off levels for distinguishing JAK2-mutated ET from "masked/prodromal" PV...
November 2016: Blood Reviews
https://www.readbyqxmd.com/read/27332908/fine-tuning-the-treatment-of-hodgkin-s-lymphoma
#19
EDITORIAL
Nancy L Bartlett
No abstract text is available yet for this article.
June 23, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/26352815/chimeric-antigen-receptor-t-cells-against-cd19-for-multiple-myeloma
#20
Alfred L Garfall, Marcela V Maus, Wei-Ting Hwang, Simon F Lacey, Yolanda D Mahnke, J Joseph Melenhorst, Zhaohui Zheng, Dan T Vogl, Adam D Cohen, Brendan M Weiss, Karen Dengel, Naseem D S Kerr, Adam Bagg, Bruce L Levine, Carl H June, Edward A Stadtmauer
A patient with refractory multiple myeloma received an infusion of CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after myeloablative chemotherapy (melphalan, 140 mg per square meter of body-surface area) and autologous stem-cell transplantation. Four years earlier, autologous transplantation with a higher melphalan dose (200 mg per square meter) had induced only a partial, transient response. Autologous transplantation followed by treatment with CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at the most recent evaluation, 12 months after treatment...
September 10, 2015: New England Journal of Medicine
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