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https://www.readbyqxmd.com/read/29764226/oral-disease-modifying-therapies-for-multiple-sclerosis-in-the-middle-eastern-and-north-african-mena-region-an-overview
#1
Dirk Deleu, Boulenouar Mesraoua, Beatriz Canibaño, Gayane Melikyan, Hassan Al Hail, Lubna El-Sheikh, Musab Ali, Hassan Al Hussein, Faiza Ibrahim, Yolande Hanssens
The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) have considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs, promote patient satisfaction and increase therapeutic adherence. This article reviews the salient features about the mode of action, efficacy, safety and tolerability profile of approved oral DMTs in RRMS and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region...
May 15, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29746722/pharmacometric-analysis-of-the-relationship-between-absolute-lymphocyte-count-and-expanded-disability-status-scale-and-relapse-rate-efficacy-end-points-in-multiple-sclerosis-trials
#2
A M Novakovic, A Thorsted, E Schindler, S Jönsson, A Munafo, M O Karlsson
The aim of this work was to assess the relationship between the absolute lymphocyte count (ALC), and disability (as measured by the Expanded Disability Status Scale [EDSS]) and occurrence of relapses, 2 efficacy endpoints, respectively, in patients with remitting-relasping multiple sclerosis. Data for ALC, EDSS, and relapse rate were available from 1319 patients receiving placebo and/or cladribine tablets. Pharmacodynamic models were developed to characterize the time course of the endpoints. ALC-related measures were then evaluated as predictors of the efficacy endpoints...
May 10, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29742076/update-on-hairy-cell-leukemia
#3
Robert J Kreitman, Evgeny Arons
Hairy cell leukemia (HCL) is a chronic B-cell malignancy with multiple treatment options, including several that are investigational. Patients present with pancytopenia and splenomegaly, owing to the infiltration of leukemic cells expressing CD22, CD25, CD20, CD103, tartrate-resistant acid phosphatase (TRAP), annexin A1 (ANXA1), and the BRAF V600E mutation. A variant lacking CD25, ANXA1, TRAP, and the BRAF V600E mutation, called HCLv, is more aggressive and is classified as a separate disease. A molecularly defined variant expressing unmutated immunoglobulin heavy variable 4-34 (IGHV4-34) is also aggressive, lacks the BRAF V600E mutation, and has a phenotype of HCL or HCLv...
March 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29720734/phase-1-2-trial-of-gclam-with-dose-escalated-mitoxantrone-for-newly-diagnosed-aml-or-other-high-grade-myeloid-neoplasms
#4
Anna B Halpern, Megan Othus, Emily M Huebner, Bart L Scott, Pamela S Becker, Mary-Elizabeth M Percival, Paul C Hendrie, Kelda M Gardner, Tara L Chen, Sarah A Buckley, Kaysey F Orlowski, Asma Anwar, Frederick R Appelbaum, Harry P Erba, Elihu H Estey, Roland B Walter
Outcomes with "7 + 3" are often unsatisfactory in acute myeloid leukemia (AML). Trials demonstrating improved outcomes with high-dose cytarabine, addition of cladribine, or escalated anthracycline doses prompted a phase 1/2 study (NCT02044796) of G-CSF, cladribine, high-dose cytarabine, and dose-escalated mitoxantrone (GCLAM) in adults with newly-diagnosed AML or other high-grade myeloid neoplasms. One hundred and twenty-one patients, median age 60 (range 21-81) years, were enrolled. In phase 1, cohorts of 6-12 patients were assigned to 12-18 mg/m2 /day of mitoxantrone as part of GCLAM...
April 17, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29716436/efficacy-of-cladribine-tablets-in-high-disease-activity-subgroups-of-patients-with-relapsing-multiple-sclerosis-a-post-hoc-analysis-of-the-clarity-study
#5
Gavin Giovannoni, Per Soelberg Sorensen, Stuart Cook, Kottil W Rammohan, Peter Rieckmann, Giancarlo Comi, Fernando Dangond, Christine Hicking, Patrick Vermersch
BACKGROUND: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. OBJECTIVE: Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3...
April 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29702970/a-new-intensive-conditioning-regimen-for-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-refractory-or-relapsed-acute-myeloid-leukemia
#6
Jingbo Wang, Jie Zhao, Xinhong Fei, Yuming Yin, Haoyu Cheng, Weijie Zhang, Jiangying Gu, Fan Yang, Yixin Yang, Song Xue, Zhengqin Tian, Junbao He, Shuqin Zhang, Xiaocan Wang
To explore the efficacy, and safety of the intensive conditioning regimen consisting of cladribine, cytarabine (Ara-C), and granulocyte colony-stimulating factor (G-CSF) plus modified busulfan (Bu) combined with cytoxan (Cy) (BuCy), prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with refractory, or relapsed acute myeloid leukemia (R/R AML).Thirty-Six R/R AML patients scheduled to receive allo-HSCT were consecutively, enrolled in this prospective study, and treated using intensive conditioning regimen consisting of CLAG plus modified BuCy...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29686117/comprehensive-systematic-review-summary-disease-modifying-therapies-for-adults-with-multiple-sclerosis-report-of-the-guideline-development-dissemination-and-implementation-subcommittee-of-the-american-academy-of-neurology
#7
Alexander Rae-Grant, Gregory S Day, Ruth Ann Marrie, Alejandro Rabinstein, Bruce A C Cree, Gary S Gronseth, Michael Haboubi, June Halper, Jonathan P Hosey, David E Jones, Robert Lisak, Daniel Pelletier, Sonja Potrebic, Cynthia Sitcov, Rick Sommers, Julie Stachowiak, Thomas S D Getchius, Shannon A Merillat, Tamara Pringsheim
OBJECTIVE: To review evidence on starting, switching, and stopping disease-modifying therapies (DMTs) for multiple sclerosis (MS) in clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and progressive MS forms. METHODS: Relevant, peer-reviewed research articles, systematic reviews, and abstracts were identified (MEDLINE, CENTRAL, EMBASE searched from inception to November 2016). Studies were rated using the therapeutic classification scheme. Prior published Cochrane reviews were also used...
April 24, 2018: Neurology
https://www.readbyqxmd.com/read/29685423/response-to-the-therapy-in-hairy-cell-leukemia-systematic-review-and-meta-analysis
#8
REVIEW
Iga Andrasiak, Justyna Rybka, Tomasz Wrobel
Hairy cell leukemia is an uncommon chronic B-cell lymphoproliferative disorder. Various treatment options are available. The objective of the study was to evaluate through meta-analysis the pooled proportions of patients responding to each therapeutic agent. We conducted a systematic review and meta-analysis to estimate the pooled response rate to modern hairy cell leukemia therapies. Articles published between January 1992 and August 2017 were identified by searching PubMed, Web of Science, and the Cochrane Library...
March 31, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29685167/neutropenia-caused-by-hairy-cell-leukemia-in-a-patient-with-myelofibrosis-secondary-to-polycythemia-vera-a-case-report
#9
Andreas Hanssønn Habberstad, Hoa Thi Tuyet Tran, Ulla Randen, Signe Spetalen, Ingunn Dybedal, Geir E Tjønnfjord, Anders Erik Astrup Dahm
BACKGROUND: Polycythemia vera is a myeloproliferative disease that sometimes evolves to myelofibrosis, causing splenomegaly and neutropenia. In this case report, we describe a patient with polycythemia vera and unexplained neutropenia who later turned out to also have hairy cell leukemia. CASE PRESENTATION: A middle-aged Caucasian man with polycythemia vera presented to our hospital with chronic mouth ulcers. Later he developed leukopenia and pancytopenia. Bone marrow biopsies showed fibrosis...
April 24, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29670776/-kit-d816v-positive-acute-mast-cell-leukemia-associated-with-normal-karyotype-acute-myeloid-leukemia
#10
Marta Lopes, Maria Dos Anjos Teixeira, Cláudia Casais, Vanessa Mesquita, Patrícia Seabra, Renata Cabral, José Palla-García, Catarina Lau, João Rodrigues, Maria Jara-Acevedo, Inês Freitas, Jose Ramón Vizcaíno, Jorge Coutinho, Luis Escribano, Alberto Orfao, Margarida Lima
Introduction: Mast cell (MC) leukemia (MCL) is extremely rare. We present a case of MCL diagnosed concomitantly with acute myeloblastic leukemia (AML). Case Report: A 41-year-old woman presented with asthenia, anorexia, fever, epigastralgia, and diarrhea. She had a maculopapular skin rash, hepatosplenomegaly, retroperitoneal adenopathies, pancytopenia, 6% blast cells (BC) and 20% MC in the peripheral blood, elevated lactate dehydrogenase, cholestasis, hypoalbuminemia, hypogammaglobulinemia, and increased serum tryptase (184  μ g/L)...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29663814/new-biological-agents-in-the-treatment-of-multiple-sclerosis
#11
M Buc
Multiple sclerosis (MS) is an inflammatory disease induced by autoimmune processes. Their understanding has resulted in an introduction of biological agents to its treatment. Interferon beta and glatiramer acetate have been in clinical practice for more than 20 years. Nowadays, novel biologics, which target molecules involved in immunopathological processes more specifically have entered the scene. They are represented by monoclonal antibodies binding to molecules VLA4 (natalizumab), CD20 (ocrelizumab), CD52 (alemtuzumab) or alpha subunit of IL-2 receptor (daclizumab) or by small molecules such as those modulating the receptors involved in regulation of lymphocyte migration (fingolimod, ozanimod) or in induction of lymphopenia by apoptosis (dimethyl fumarate, cladribine)...
2018: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29653214/poly-propylene-imine-glycodendrimers-non-covalently-bind-atp-in-a-ph-and-salt-dependent-manner-model-studies-for-adenosine-analogue-drug-delivery
#12
Michał Gorzkiewicz, Adam Buczkowski, Dietmar Appelhans, Brigitte Voit, Łukasz Pułaski, Bartłomiej Pałecz, Barbara Klajnert-Maculewicz
Adenosine analogue drugs (such as fludarabine or cladribine) require transporter-mediated uptake into cells and subsequent phosphorylation for anticancer activity. Therefore, application of nanocarrier systems for direct delivery of active triphosphate nucleotides has been proposed. Here, we applied isothermal titration calorimetry (ITC) and zeta potential titration to determine the stoichiometry and thermodynamic parameters of interactions between 4th generation poly(propylene imine) (PPI G4) dendrimers (unmodified or sugar-modified for increased biocompatibility) and ATP as a model adenosine nucleotide...
April 10, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29618273/cost-effectiveness-of-cladribine-tablets-alemtuzumab-and-natalizumab-in-the-treatment-of-relapsing-remitting-multiple-sclerosis-with-high-disease-activity-in-england
#13
Robert Hettle, Gerard Harty, Schiffon L Wong
AIMS: Cladribine tablets is the first oral short-course treatment approved for highly active relapsing multiple sclerosis (MS). The Association of British Neurologists guidelines currently recommend two infusion therapies, alemtuzumab and natalizumab, to treat high disease activity relapsing remitting MS (HDA-RRMS). This analysis assessed the cost-effectiveness of cladribine tablets in HDA-RRMS compared with alemtuzumab and natalizumab, from the perspective of the National Health Service (NHS) in England...
April 5, 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29600441/efficacy-and-safety-of-the-newer-multiple-sclerosis-drugs-approved-since-2010
#14
REVIEW
Simon Faissner, Ralf Gold
Multiple sclerosis treatment faces tremendous changes as a result of the approval of new medications. The new medications have differing safety considerations and risks after long-term treatment, which are important for treating physicians to optimize and individualize multiple sclerosis care. Since the approval of the first multiple sclerosis capsule, fingolimod, the armamentarium of multiple sclerosis therapy has grown with the orally available medications dimethyl fumarate and teriflunomide. Fingolimod is mainly associated with cardiac side effects, dimethyl fumarate with bowel symptoms...
March 2018: CNS Drugs
https://www.readbyqxmd.com/read/29574395/acute-myeloid-leukemia-induction-with-cladribine-outcomes-by-age-and-leukemia-risk
#15
Martin W Schoen, Susan K Woelich, James T Braun, Dhinesh V Reddy, Mark J Fesler, Paul J Petruska, Carl E Freter, Jack M Lionberger
Acute myeloid leukemia (AML) induction traditionally includes seven days of cytarabine and three days of an anthracycline (7 + 3). Because of evidence of increased efficacy of cladribine combined with this regimen, we conducted a retrospective analysis of 107 AML patients treated with idarubicin, cytarabine and cladribine (IAC) at our institution. Complete remission (CR) occurred in 71%, with overall response of 79%. One-year survival overall was 59%, with 47% (27/57) among patients ≥60 years old and 72% (36/50) in those <60 (Relative Risk [RR] 1...
May 2018: Leukemia Research
https://www.readbyqxmd.com/read/29562470/-cladribine-in-treatment-of-5-patients-with-hairy-cell-leukemia
#16
Z Y Liu, Y Chen, Y B Chen, Z Y Yan, Y Wang, J M Li, H M Sun, S J Zhang
No abstract text is available yet for this article.
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29550884/cladribine-treatment-of-multiple-sclerosis-is-associated-with-depletion-of-memory-b-cells
#17
Bryan Ceronie, Benjamin M Jacobs, David Baker, Nicolas Dubuisson, Zhifeng Mao, Francesca Ammoscato, Helen Lock, Hilary J Longhurst, Gavin Giovannoni, Klaus Schmierer
BACKGROUND: The mechanism of action of oral cladribine, recently licensed for relapsing multiple sclerosis, is unknown. OBJECTIVE: To determine whether cladribine depletes memory B cells consistent with our recent hypothesis that effective, disease-modifying treatments act by physical/functional depletion of memory B cells. METHODS: A cross-sectional study examined 40 people with multiple sclerosis at the end of the first cycle of alemtuzumab or injectable cladribine...
March 17, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29523912/-cladribine-tablets-oral-immunotherapy-of-relapsing-remitting-multiple-sclerosis-with-short-yearly-treatment-periods
#18
REVIEW
S G Meuth, T Ruck, O Aktas, H-P Hartung
BACKGROUND: The selective modulation of lymphocyte numbers and function is an attractive concept in the treatment of relapsing-remitting multiple sclerosis (RMS). OBJECTIVE: Cladribine tablets (Mavenclad®), an oral RMS medication with an innovative treatment concept, have been available since August 2017. This review article summarizes the currently available clinical study data on cladribine tablets and aspects of their use in clinical practice. RESULTS: Cladribine tablets are administered during two treatment phases of 8-10 (two times 4-5) days with a 1-year interval...
March 9, 2018: Der Nervenarzt
https://www.readbyqxmd.com/read/29501513/-rosai-dorfman-disease-diagnosis-and-therapeutic-challenges
#19
F Cohen Aubart, J Haroche, J-F Emile, F Charlotte, S Barete, N Schleinitz, J Donadieu, Z Amoura
Rosai-Dorfman disease (RDD) was first described by the French pathologist Paul Destombes in 1965. It frequently affects children or young adults and is characterized by the presence of large histiocytes with emperipolesis. More than 50 years after this first description, the pathogenesis of this rare disease is still poorly understood. The revised classification of histiocytoses published in 2016 identified various forms of RDD, from familial RDD to IgG4-associated RDD. Almost 90% of the patients with RDD have cervical lymph nodes involvement although all the organs may virtually be involved...
February 28, 2018: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29500302/oral-therapies-for-multiple-sclerosis
#20
Simon Faissner, Ralf Gold
Multiple sclerosis treatment faces tremendous changes owing to the approval of new medications, some of which are available as oral formulations. Until now, the four orally available medications, fingolimod, dimethylfumarate (BG-12), teriflunomide, and cladribine have received market authorization, whereas laquinimod is still under development. Fingolimod is a sphingosine-1-phosphate inhibitor, which is typically used as escalation therapy and leads to up to 60% reduction of the annualized relapse rate, but might also have neuroprotective properties...
March 2, 2018: Cold Spring Harbor Perspectives in Medicine
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