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https://www.readbyqxmd.com/read/28647672/therapeutic-targeting-of-nuclear-export-inhibition-in-lung-cancer
#1
Arjun Gupta, Jessica M Saltarski, Michael A White, Pier P Scaglioni, David E Gerber
Intracellular compartmentalization and trafficking of molecules plays a critical role in complex and essential cellular processes. In lung cancer and other malignancies, aberrant nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators results in tumorigenesis and inactivation of apoptosis. Pharmacologic targeting of this process, termed selective inhibition of nuclear export (SINE), has demonstrated anti-tumor efficacy in preclinical models and human clinical trials. Exportin-1 (XPO1)-which serves as the sole exporter of several tumor suppressor proteins and cell cycle regulators, including retinoblastoma (Rb), adenomatous polyposis coli (APC), p53, p73, p21, p27, FOXO, STAT3, IKB, topoisomerase II and PAR-4-is the principal focus of SINE drug development...
June 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28647558/durable-chimerism-and-long-term-survival-following-unrelated-umbilical-cord-blood-transplantation-for-pediatric-hemophagocytic-lymphohistiocytosis-a-single-center-experience
#2
Sachit A Patel, Heather A Allewelt, Jesse D Troy, Paul L Martin, Timothy A Driscoll, Vinod K Prasad, Joanne Kurtzberg, Kristin M Page, Suhag H Parikh
Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, CNS disease, increased inflammatory markers and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH with reported survival ranging from 50-70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplant related mortality associated with conventional MAC are major barriers to success...
June 21, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28646772/prevalence-of-immune-related-systemic-adverse-events-in%C3%A2-patients-treated-with-anti-programmed-cell-death-1-anti-programmed-cell-death-ligand-1-agents-a-single-centre-pharmacovigilance-database-analysis
#3
Sébastien Le Burel, Stéphane Champiat, Christine Mateus, Aurélien Marabelle, Jean-Marie Michot, Caroline Robert, Rakiba Belkhir, Jean-Charles Soria, Salim Laghouati, Anne-Laure Voisin, Olivier Fain, Arsène Mékinian, Laetitia Coutte, Tali-Anne Szwebel, Laetitia Dunogeant, Bertrand Lioger, Cécile Luxembourger, Xavier Mariette, Olivier Lambotte
AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)(1) a French registry of grade ≥2 irAEs occurring in ICI-treated patients...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28646676/multicenter-phase-2-study-of-combination-therapy-with-ruxolitinib-and-danazol-in-patients-with-myelofibrosis
#4
K Gowin, H Kosiorek, A Dueck, J Mascarenhas, R Hoffman, C Reeder, J Camoriano, R Tibes, K Gano, J Palmer, R Mesa
Myelofibrosis is a myeloproliferative neoplasm that is characterized by splenomegaly, profound symptom burden, and cytopenias. JAK inhibitor therapy offers improvements in splenomegaly, symptom burden, and potentially survival; however, cytopenias remain a significant challenge. Danazol has previously demonstrated improvements in myelofibrosis-associated anemia. We conducted a phase II clinical trial evaluating the efficacy and tolerability of combination therapy with ruxolitinib, an oral JAK inhibitor, and danazol...
June 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28642120/transfusion-challenges-in-hematology-oncology-and-hematopoietic-stem-cell-transplant-literature-review-and-local-experience
#5
REVIEW
Mohamed Elemary, Jerard Seghatchian, Julie Stakiw, Mark Bosch, Waleed Sabry, Hadi Goubran
Transfusion medicine plays a vital role in the supportive care of patients receiving therapy for hematology, oncology and hematopoietic stem cell transplants (HSCT). With advances in therapy with more intensive chemotherapy or radiotherapy, patients usually develop cytopenias and need frequent transfusion support with packed red blood cells, granulocyte transfusion or platelets to support them until they recover from the effect of therapy. HSCT poses unique challenges for transfusion medicine, since transplant recipients may require substantial transfusion support due to cytopenias associated with toxic medications, decreased marrow reserve, infection or their malignancy...
June 3, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28638678/detailed-features-of-hematological-involvement-and-medication-induced-cytopenia-in-systemic-lupus-erythematosus-patients-single-center-results-of-221-patients
#6
Hava Üsküdar Teke, Döndü Üsküdar Cansu, Cengiz Korkmaz
OBJECTIVE: Systemic lupus erythematosus (SLE) may affect a number of systems, with the hematological system being one of the most common. Our aim is to determine the existence of cytopenia at diagnosis or during follow-up of our SLE patients as well as the associated factors. MATERIAL AND METHODS: A cohort of SLE patients that had been followed-up in the Department of Rheumotology from 1998 to 2015 was retrospectively assessed. Clinical and laboratory findings about the patients were recorded...
June 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28637621/gata2-deficiency-and-related-myeloid-neoplasms
#7
Marcin W Wlodarski, Matthew Collin, Marshall S Horwitz
The GATA2 gene codes for a hematopoietic transcription factor that through its two zinc fingers (ZF) can occupy GATA-DNA motifs in a countless number of genes. It is crucial for the proliferation and maintenance of hematopoietic stem cells. During the past 5 years, germline heterozygous mutations in GATA2 were reported in several hundred patients with various phenotypes ranging from mild cytopenia to severe immunodeficiency involving B cells, natural killer cells, CD4(+) cells, monocytes and dendritic cells (MonoMAC/DCML), and myeloid neoplasia...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637619/practical-considerations-for-diagnosis-and-management-of-patients-and-carriers
#8
REVIEW
Charlotte M Niemeyer, Cristina Mecucci
Newly diagnosed children and adults with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) need to be screened for presence of a genetic predisposition syndrome because the information on the genetic status is likely to influence clinical care and management of the patient and the family. Scenarios in which genetic counseling is advised include presence of a mutation on somatic screen that can be associated with a germline predisposition, hematologic or cytogenetic characteristics suggestive of an underlying susceptibility syndrome, non-hematological phenotype suspicious for a familial condition, history of previous malignancy, or a family history of cancer, cytopenia, autoimmunity, or organ-system manifestation fitting a predisposition syndrome...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28626543/cerebral-stroke-in-a-teenage-girl-with-paroxysmal-nocturnal-hemoglobinuria
#9
Francesco Gervasi, Lucia D'Amelio, Antonino Trizzino, Fabrizia Ferraro, Delia Russo, Giuseppe Santangelo, Francesca Cardella, Angela Trizzino, Floriana Di Marco, Piero Farruggia
We report a case of paroxysmal nocturnal hemoglobinuria (PNH) in a 14 year-old girl presenting a cerebral arterial thrombosis. The initial diagnosis was carential anemia due to menarche following identification of slight macrocytic anemia, leucopenia and mild thrombocytopenia at routine blood analysis. The child was eventually referred to a children's hospital after the onset of progressive fatigue, anorexia and paleness. Severe anemia (hemoglobin 6 g/dL) with negative Coombs test, mild leucopenia (white blood cells 4...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28603827/prognostic-factors-predicting-overall-survival-in-moroccan-patients-with-myelodysplastic-syndrome
#10
Selim Jennane, Sanae Amelal, Mahtat El Mehdi, Samir Ahid, Nezha Messaoudi, Kamal Doghmi, Mohammed Mikdame
BACKGROUND: Prognostic scores are an indispensable tool in the management of myelodysplastic syndromes. AIM: Identify prognostic factors influencing overall survival of patients with myelodysplastic syndromes. METHODS: We included all patients with myelodysplastic syndromes treated in the clinical hematology department of the military hospital of Rabat (Morocco). RESULTS: Seventy-four patients were included. The sex ratio [M / F] was 1...
August 2016: La Tunisie Médicale
https://www.readbyqxmd.com/read/28602585/janus-kinase-2-inhibitor-fedratinib-in-patients-with-myelofibrosis-previously-treated-with-ruxolitinib-jakarta-2-a-single-arm-open-label-non-randomised-phase-2-multicentre-study
#11
Claire N Harrison, Nicolaas Schaap, Alessandro M Vannucchi, Jean-Jacques Kiladjian, Ramon V Tiu, Pierre Zachee, Eric Jourdan, Elliott Winton, Richard T Silver, Harry C Schouten, Francesco Passamonti, Sonja Zweegman, Moshe Talpaz, Joanne Lager, Zhenming Shun, Ruben A Mesa
BACKGROUND: Myelofibrosis is a chronic myeloproliferative neoplasm characterised by splenomegaly, cytopenias, bone marrow fibrosis, and debilitating symptoms including fatigue, weight loss, and bone pain. Mutations in Janus kinase-2 (JAK2) occur in approximately 50% of patients. The only approved JAK2 inhibitor for myelofibrosis is the dual JAK1 and JAK2 inhibitor, ruxolitinib. 58-71% of patients treated with ruxolitinib in clinical trials so far have not achieved the primary endpoint of 35% or more reduction in spleen volume from baseline assessed by MRI or CT...
June 8, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28601896/influence-of-tnf-and-il6-gene-polymorphisms-on-the-severity-of-cytopenias-in-argentine-patients-with-myelodysplastic-syndromes
#12
Yesica Bestach, Virginia Palau Nagore, María G Flores, Jacqueline González, Jorge Arbelbide, Nora Watman, Yamila Sieza, Irene Larripa, Carolina Belli
Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (-308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (-174 G/C), and TGFB1 (+869 C/T and +915 G/C)...
June 10, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28597691/safety-and-efficacy-of-pegfilgrastim-when-given-less-than-14-days-before-the-next-chemotherapy-cycle-retrospective-review-of-every-14-day-chemotherapy-regimen-containing-5-fu-continuous-infusion
#13
Kofi N Donkor, Julie H Selim, Ariani Waworuntu, Kelsey Lewis
BACKGROUND: Pegfilgrastim should not be given <14 days from the next chemotherapy because of concerns for cytopenias. Some clinicians are prescribing pegfilgrastim to be given <14 days in patients receiving 5-fluorouracil continuous infusion (5-FUCI) regimens. OBJECTIVE: To determine the effectiveness and safety of pegfilgrastim administered <14 days from the next chemotherapy in patients receiving 5-FUCI administered >46 hours. METHODS: Single-institution retrospective cohort study of patients who received 5-FUCI administered >46 hours from June 2013 to December 2015...
June 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28596252/success-in-bone-marrow-failure-novel-therapeutic-directions-based-on-the-immune-environment-of-myelodysplastic-syndromes
#14
REVIEW
Alyssa H Cull, Michael J Rauh
Myelodysplastic syndromes (MDS) are clonal neoplasms of aging that are associated with BM failure, related cytopenias, fatigue, susceptibility to infections, bruising, bleeding, a shortened lifespan, and a propensity for leukemic transformation. Most frail, elderly patients are not candidates for curative allogeneic BM transplantations and instead receive expectant management, supportive blood transfusions, or empirical, nontargeted therapy. It has been known for some time that MDS arises in an abnormal BM immune environment; however, connections have only recently been established with recurring MDS-associated mutations...
June 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28591503/-cytogenetics-of-myelodysplastic-syndromes-and-its-impact-as-prognostic-factor
#15
César Borjas-Gutiérrez, Martín Daniel Domínguez-Cruz, Juan Ramón González-García
Myelodysplastic syndromes (MDS) are a group of disorders of the hematopoietic stem cell. They are characterized by cytopenia(s), dysplasia of one or more cell lines, ineffective hematopoiesis, and an increased risk for developing acute myelogenous leukemia. The classification of MDS has been complicated due to the great heterogeneity in clinical phenotype as well as in the morphological and cytogenetic characteristics. The prognostic value of cytogenetic abnormalities in MDS has been analyzed in multicenter studies...
July 2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28588809/cytopenia-first-hepatitis-second-an-unusual-sequence-in-aplastic-anemia
#16
Ferras Alashkar, Daniel Föhring, Ulrich Dührsen, Hideo Andreas Baba, Alexander Röth
To the best of our knowledge, this is the first report of aplastic anemia (AA) preceding autoantibody-negative autoimmune hepatitis (AIH) with successful treatment of both conditions with the same immunosuppressive regimen, resulting in hematopoietic reconstitution and remission of AIH.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28588781/p53-protein-expression-in-patients-with-myelodysplasia-treated-with-allogeneic-bone-marrow-transplantation
#17
Achille Pich, Laura Godio, Laura Davico Bonino
Tumor protein 53 mutations adversely affect the prognosis of myelodysplastic syndromes (MDS); however, few studies have reported on the prognostic significance of the expression of p53 protein in MDS. The current study investigated p53 immunoreactivity (p53-IR) in bone marrow biopsies (BMBs) obtained at diagnosis from 18 patients (6 females and 12 males; mean age, 50.5 years) with MDS that underwent bone marrow transplantation (BMT) to determine the associations between clinical and histopathological data and outcome...
June 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28588322/a-phase-ib-study-of-pembrolizumab-plus-chemotherapy-in-patients-with-advanced-cancer-pembroplus
#18
Glen J Weiss, Jordan Waypa, Lisa Blaydorn, Jessica Coats, Kayla McGahey, Ashish Sangal, Jiaxin Niu, Cynthia A Lynch, John H Farley, Vivek Khemka
BACKGROUND: Pembrolizumab (P) is an anti-PD-1 antibody that blocks the interaction between programmed cell death protein 1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumour cells. A phase Ib trial of P plus chemotherapy was undertaken to evaluate the safety and efficacy. METHODS: Patients with advanced, metastatic solid tumours were enrolled onto one of six treatment arms. Pembrolizumab was given: with gemcitabine (G), G+docetaxel (D), G+nab-paclitaxel (NP), G+vinorelbine (V) or irinotecan (I) until progression or toxicity, or with liposomal doxorubicin (LD) for up to 15 cycles, progression or toxicity...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28586251/the-relationship-between-idiopathic-cytopenias-dysplasias-of-uncertain-significance-icus-idus-and-autoimmunity
#19
Wilma Barcellini
This review examines the several lines of evidence that support the relationship between myelodysplasia and autoimmunity, i.e. their epidemiologic association, the existence of common immune-mediated physiopathologic mechanisms, and the response to similar immunosuppressive therapies. The same relationship is reviewed here considering idiopathic cytopenia of uncertain significance (ICUS) and idiopathic dysplasia of uncertain significance (IDUS), two recently recognized provisional conditions characterized by isolated/unexplained cytopenia and/or dysplasia in <10% bone marrow cells...
June 15, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28583781/-macrophage-activation-syndrome-and-kawasaki-disease-four-new-cases
#20
B Dumont, P Jeannoel, L Trapes, E Rolland, C Gay, J-L Stephan
Macrophage activation syndrome (MAS) is a rarely reported complication of Kawasaki disease (KD). It must be sought during KD with unusual clinical signs, such as enlargement of the liver or spleen, cytopenia (including thrombocytopenia), and elevated serum triglycerides. Here, we report four cases from a single center. The first is the description of a case of KD occurring in an 11-month-old child 15 days after the occurrence of infectious spondylitis. For the second, acute myocarditis heralded KD in a 5-year-old child...
June 2, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
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