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Leukemia

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34 papers 100 to 500 followers
https://www.readbyqxmd.com/read/29110361/hairy-cell-leukemia-2018-update-on-diagnosis-risk-stratification-and-treatment
#1
Xavier Troussard, Edouard Cornet
DISEASE OVERVIEW: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. DIAGNOSIS: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation...
December 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29102721/cellular-immunotherapy-for-haematological-malignancies-beyond-bone-marrow-transplant
#2
REVIEW
Melita Cirillo, Peter Tan, Marian Sturm, Catherine Cole
Immunotherapy has changed treatment practices for many haematological malignancies. Despite the current era of targeted therapy, chemotherapy remains the backbone of treatment for many haematological malignancies, especially in acute leukaemia, where relapse remains the major cause of mortality. Application of novel immunotherapies in haematology attempts to harness the killing power of the immune system against leukaemia and lymphoma. Cellular immunotherapy is evolving rapidly for high risk haematological disorders...
November 1, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28644114/midostaurin-plus-chemotherapy-for-acute-myeloid-leukemia-with-a-flt3-mutation
#3
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
#4
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/28572287/how-i-treat-chronic-myelomonocytic-leukemia
#5
REVIEW
Eric Solary, Raphael Itzykson
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that may deserve specific management. Defined by a persistent peripheral blood monocytosis ≥1 × 10(9)/L and monocytes accounting for ≥10% of the white blood cells, this aging-associated disease combines cell proliferation as a consequence of myeloid progenitor hypersensitivity to granulocyte-macrophage colony-stimulating factor with myeloid cell dysplasia and ineffective hematopoiesis. The only curative option for CMML remains allogeneic stem cell transplantation...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/21505136/use-of-whole-genome-sequencing-to-diagnose-a-cryptic-fusion-oncogene
#6
John S Welch, Peter Westervelt, Li Ding, David E Larson, Jeffery M Klco, Shashikant Kulkarni, John Wallis, Ken Chen, Jacqueline E Payton, Robert S Fulton, Joelle Veizer, Heather Schmidt, Tammi L Vickery, Sharon Heath, Mark A Watson, Michael H Tomasson, Daniel C Link, Timothy A Graubert, John F DiPersio, Elaine R Mardis, Timothy J Ley, Richard K Wilson
CONTEXT: Whole-genome sequencing is becoming increasingly available for research purposes, but it has not yet been routinely used for clinical diagnosis. OBJECTIVE: To determine whether whole-genome sequencing can identify cryptic, actionable mutations in a clinically relevant time frame. DESIGN, SETTING, AND PATIENT: We were referred a difficult diagnostic case of acute promyelocytic leukemia with no pathogenic X-RARA fusion identified by routine metaphase cytogenetics or interphase fluorescence in situ hybridization (FISH)...
April 20, 2011: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28205134/minimal-residual-disease-in-acute-lymphoblastic-leukemia-how-to-recognize-and-treat-it
#7
REVIEW
Nicholas J Short, Elias Jabbour
In recent years, the identification of minimal residual disease (MRD) that persists after chemotherapy has emerged as the most powerful tool in determining the prognosis of patients with ALL, often superseding historically relevant prognostic factors. Multiple methods to detect MRD exist, each with their own advantages and disadvantages. Multiparameter flow cytometry and quantitative polymerase chain reaction are the most commonly used methods of MRD detection in clinical practice, although there is promise in the use of more sensitive assays utilizing next-generation sequencing that may be able to further refine MRD-based risk stratification...
January 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28357672/overview-of-targeted-therapies-for-adult-t-cell-leukemia-lymphoma
#8
Rihab Nasr, Ambroise Marçais, Olivier Hermine, Ali Bazarbachi
Adult T-Cell Leukemia/lymphoma (ATL) is the first human malignancy associated with a chronic infection by a retrovirus, the human T-cell lymphotropic virus type I (HTLV-I). ATL occurs, after a long latency period, only in about 5% of 10-20 millions infected individuals. ATL has a dismal prognosis with a median survival of less than 1 year, mainly due to its resistance to chemotherapy and to a profound immunosuppression. The viral oncoprotein, Tax, plays a major role in ATL oncogenic transformation by interfering with cell proliferation, cell cycle, apoptosis, and DNA repair...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28254820/3-7-flt3-inhibitors-1-1-%C3%A2-2
#9
Richard M Stone
No abstract text is available yet for this article.
March 2, 2017: Blood
https://www.readbyqxmd.com/read/28325865/venetoclax-and-obinutuzumab-in-chronic-lymphocytic-leukemia
#10
LETTER
Kirsten Fischer, Othman Al-Sawaf, Anna-Maria Fink, Mark Dixon, Jasmin Bahlo, Simon Warburton, Thomas J Kipps, Robert Weinkove, Sue Robinson, Till Seiler, Stephen Opat, Carolyn Owen, Javier López, Kathryn Humphrey, Rod Humerickhouse, Eugen Tausch, Lukas Frenzel, Barbara Eichhorst, Clemens-M Wendtner, Stephan Stilgenbauer, Anton W Langerak, Jacque J M van Dongen, Sebastian Böttcher, Matthias Ritgen, Valentin Goede, Mehrdad Mobasher, Michael Hallek
No abstract text is available yet for this article.
May 11, 2017: Blood
https://www.readbyqxmd.com/read/28297625/genomics-of-hairy-cell-leukemia
#11
REVIEW
Enrico Tiacci, Valentina Pettirossi, Gianluca Schiavoni, Brunangelo Falini
Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28297624/genomics-of-acute-myeloid-leukemia-diagnosis-and-pathways
#12
REVIEW
Lars Bullinger, Konstanze Döhner, Hartmut Döhner
In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28297623/clinical-implications-of-novel-genomic-discoveries-in-chronic-lymphocytic-leukemia
#13
REVIEW
Gregory Lazarian, Romain Guièze, Catherine J Wu
Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy with a remarkably heterogeneous course, ranging from indolent disease with no need for immediate therapy to rapidly progressive disease associated with therapeutic resistance. The recent US Food and Drug Administration approvals of novel targeted therapies such as inhibitors of B-cell receptor signaling and B-cell lymphoma 2 have opened up new opportunities in the clinical management of patients with CLL and heralded a new era in the clinical treatment of this disease...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27903528/consensus-guidelines-for-the-diagnosis-and-management-of-patients-with-classic-hairy-cell-leukemia
#14
Michael R Grever, Omar Abdel-Wahab, Leslie A Andritsos, Versha Banerji, Jacqueline Barrientos, James S Blachly, Timothy G Call, Daniel Catovsky, Claire Dearden, Judit Demeter, Monica Else, Francesco Forconi, Alessandro Gozzetti, Anthony D Ho, James B Johnston, Jeffrey Jones, Gunnar Juliusson, Eric Kraut, Robert J Kreitman, Loree Larratt, Francesco Lauria, Gerard Lozanski, Emili Montserrat, Sameer A Parikh, Jae H Park, Aaron Polliack, Graeme R Quest, Kanti R Rai, Farhad Ravandi, Tadeusz Robak, Alan Saven, John F Seymour, Tamar Tadmor, Martin S Tallman, Constantine Tam, Enrico Tiacci, Xavier Troussard, Clive S Zent, Thorsten Zenz, Pier Luigi Zinzani, Brunangelo Falini
Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/28064238/myeloid-malignancies-and-the-microenvironment
#15
Claudia Korn, Simón Méndez-Ferrer
Research in the last few years has revealed a sophisticated interaction network between multiple bone marrow cells that regulate different hematopoietic stem cell (HSC) properties such as proliferation, differentiation, localization, and self-renewal during homeostasis. These mechanisms are essential to keep the physiological HSC numbers in check and interfere with malignant progression. In addition to the identification of multiple mutations and chromosomal aberrations driving the progression of myeloid malignancies, alterations in the niche compartment recently gained attention for contributing to disease progression...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28159738/therapeutic-targeting-of-acute-myeloid-leukemia-stem-cells
#16
REVIEW
Daniel A Pollyea, Craig T Jordan
For more than 50 years, investigators have considered a malignant stem cell as the potential origin of and a key therapeutic target for acute myeloid leukemia (AML) and other forms of cancer.(1-4) The nature and existence of tumor-initiating cells for leukemia and other malignancies have long been the subject of intense and rigorous study; indeed, the promise of the potential to eradicate such cells is clear. However, until recently, deficiencies in our understanding of the nature of these cell populations, coupled with a limited ability to therapeutically exploit their weaknesses, have been limiting factors in realizing the goal of targeting leukemic stem cells (LSCs)...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/27385790/integrating-clinical-features-and-genetic-lesions-in-the-risk-assessment-of-patients-with-chronic-myelomonocytic-leukemia
#17
Chiara Elena, Anna Gallì, Esperanza Such, Manja Meggendorfer, Ulrich Germing, Ettore Rizzo, Jose Cervera, Elisabetta Molteni, Annette Fasan, Esther Schuler, Ilaria Ambaglio, Maria Lopez-Pavia, Silvia Zibellini, Andrea Kuendgen, Erica Travaglino, Reyes Sancho-Tello, Silvia Catricalà, Ana I Vicente, Torsten Haferlach, Claudia Haferlach, Guillermo F Sanz, Luca Malcovati, Mario Cazzola
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm with variable clinical course. To predict the clinical outcome, we previously developed a CMML-specific prognostic scoring system (CPSS) based on clinical parameters and cytogenetics. In this work, we tested the hypothesis that accounting for gene mutations would further improve risk stratification of CMML patients. We therefore sequenced 38 genes to explore the role of somatic mutations in disease phenotype and clinical outcome...
September 8, 2016: Blood
https://www.readbyqxmd.com/read/28115371/management-of-adults-with-t-cell-lymphoblastic-leukemia
#18
REVIEW
David I Marks, Clare Rowntree
T-cell acute lymphoblastic leukemia (ALL) is a rare disease in adults with inferior survival outcomes compared with those seen in pediatric patients. Although potentially curable with ∼50% survival at 5 years, adult patients with relapsed disease have dismal outcomes with <10% of patients surviving long term. This review will discuss the diagnosis and management of adult patients with newly diagnosed T-cell ALL with an emphasis on the immunophenotypic and genetic analyses required to assign prognosis, risk stratify, and guide post-remission therapy...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/27872057/how-i-treat-flt3-mutated-aml
#19
Keith W Pratz, Mark Levis
FLT3-mutated acute myeloid leukemia (AML), despite not being recognized as a distinct entity in the World Health Organization (WHO) classification system, is readily recognized as a particular challenge by clinical specialists who treat acute leukemia. This is especially true with regards to the patients harboring the most common type of FLT3 mutation, the internal tandem duplication (FLT3-ITD) mutation. Here we present 4 patient cases from our institution and discuss how our management reflects what we have learned about this subtype of the disease...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/28096090/how-i-manage-ibrutinib-refractory-chronic-lymphocytic-leukemia
#20
REVIEW
Jennifer A Woyach
The introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has dramatically changed the management of chronic lymphocytic leukemia (CLL). Although responses have been durable in the majority of patients, relapses do occur, especially in the high-risk patient population. Most relapses occur as the result of acquired mutations in BTK and PLCG2, which may facilitate success with alternative targeted therapies. As outcomes after ibrutinib relapse have been reported to be poor, specific strategies are needed for this patient population...
March 9, 2017: Blood
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