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Cladribine

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https://www.readbyqxmd.com/read/29149804/systematic-literature-review-and-network-meta-analysis-of-cladribine-tablets-versus-alternative-disease-modifying-treatments-for-relapsing-remitting-multiple-sclerosis
#1
M K Siddiqui, I S Khurana, S Budhia, R Hettle, G Harty, S L Wong
OBJECTIVE: To assess the comparative efficacy and safety of cladribine tablets versus alternative disease modifying treatments (DMTs) in patients with active relapsing-remitting multiple sclerosis (RRMS), and in a subgroup with high disease activity (HRA+DAT), using systematic literature review (SLR) and network meta-analysis (NMA). METHODS: MEDLINE, Embase, MEDLINE In-Process and CENTRAL databases were systematically searched to identify English-language publications of relevant studies of approved DMTs for RRMS...
November 17, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29137311/crenolanib-is-a-type-i-tyrosine-kinase-inhibitor-that-inhibits-mutant-kit-d816-isoforms-prevalent-in-systemic-mastocytosis-and-core-binding-factor-leukemia
#2
Kerstin Maria Kampa-Schittenhelm, Julia Frey, Lara A Haeusser, Barbara Illing, Ashly A Pavlovsky, Gunnar Blumenstock, Marcus Matthias Schittenhelm
Activating D816 mutations of the class III receptor tyrosine kinase KIT are associated with the majority of patients with systemic mastocytosis (SM), but also core binding factor (CBF) AML, making KIT mutations attractive therapeutic targets for the treatment of these cancers. Crenolanib is a potent and selective inhibitor of wild-type as well as mutant isoforms of the class III receptor tyrosine kinases FLT3 and PDGFRα/β. Notably, crenolanib inhibits constitutively active mutant-FLT3 isoforms resulting from amino acid substitutions of aspartic acid at codon 835, which is homologous to codon 816 in the KIT gene - suggesting sensitivity against mutant-KIT D816 isoforms as well...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100976/a-comparison-of-clofarabine-based-gclac-and-cladribine-based-clag-salvage-chemotherapy-for-relapsed-refractory-aml
#3
Benyam Muluneh, Kaitlyn Buhlinger, Allison M Deal, Joshua F Zeidner, Matthew C Foster, Katarzyna Joanna Jamieson, Jill Bates, Hendrik W Van Deventer
BACKGROUND: Salvage regimens for patients with relapsed/refractory acute myeloid leukemia (rrAML) lack comparative data for superiority. Thus, we conducted a retrospective analysis of clofarabine-based (GCLAC; granulocyte colony-stimulating factor [filgrastim], clofarabine, high-dose cytarabine) versus cladribine-based (CLAG; cladribine, cytarabine, granulocyte colony-stimulating factor [filgrastim]) regimens in rrAML. PATIENTS AND METHODS: We identified 41 consecutive patients with rrAML who had received either GCLAC or CLAG from 2011 to 2014...
September 22, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29083024/pulmonary-langerhans-cell-histiocytosis-in-adults
#4
Elżbieta Radzikowska
Pulmonary Langerhans' cell histiocytosis (PLCH) is a rare disorder of unknown cause characterised by the infiltration of the lungs and other organs by the bone marrow derived Langerhans' cells, which carry mutations of BRAF gene and/or NRAS, KRAS and MAP2K1 genes. It occurs predominantly in young smokers, without gender predominance. The disease is characterised by formation of eosinophilic granulomas with the presence of Langerhans' cells infiltrating and destroying distal airways. High-resolution computed tomography of the chest (HRCT) plays an outstanding role in PLCH diagnosis...
October 30, 2017: Advances in Respiratory Medicine
https://www.readbyqxmd.com/read/29056470/phase-2-open-label-study-of-bortezomib-cladribine-and-rituximab-in-advanced-newly-diagnosed-and-relapsed-refractory-mantle-cell-and-indolent-lymphomas
#5
Soham D Puvvada, José Guillen-Rodriguez, Abhijeet Kumar, Lora Inclán, Kara Heard, Xavier I Rivera, Faiz Anwer, Jonathan H Schatz, Daruka Mahadevan, Daniel O Persky
BACKGROUND: Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). PATIENTS AND METHODS: Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29051829/the-efficacy-of-cladribine-tablets-in-cis-patients-retrospectively-assigned-the-diagnosis-of-ms-using-modern-criteria-results-from-the-oracle-ms-study
#6
Mark S Freedman, Thomas P Leist, Giancarlo Comi, Bruce Ac Cree, Patricia K Coyle, Hans-Peter Hartung, Patrick Vermersch, Doris Damian, Fernando Dangond
BACKGROUND: Multiple sclerosis (MS) diagnostic criteria have changed since the ORACLE-MS study was conducted; 223 of 616 patients (36.2%) would have met the diagnosis of MS vs clinically isolated syndrome (CIS) using the newer criteria. OBJECTIVE: The objective of this paper is to assess the effect of cladribine tablets in patients with a first clinical demyelinating attack fulfilling newer criteria (McDonald 2010) for MS vs CIS. METHODS: A post hoc analysis for subgroups of patients retrospectively classified as fulfilling or not fulfilling newer criteria at the first clinical demyelinating attack was conducted...
October 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/29036962/-cladribine-in-the-treatment-of-tet2-refractory-acute-myeloid-leukemia-a-case-report
#7
J Liu, R Guo, Z X Jiang
No abstract text is available yet for this article.
October 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29030092/a-phase-ii-study-of-clag-regimen-combined-with-imatinib-mesylate-for-relapsed-or-refractory-acute-myeloid-leukemia
#8
Abu-Sayeef Mirza, Jeffrey E Lancet, Kendra Sweet, Eric Padron, Javier Pinilla-Ibarz, Lisa Nardelli, Christopher Cubitt, Alan F List, Rami S Komrokji
INTRODUCTION: No standard salvage chemotherapy regimen is available for relapsed or refractory (RR) acute myeloid leukemia (AML). Preclinical data have suggested synergy in vitro between cytarabine and imatinib mesylate (IM) on AML cell growth inhibition. After demonstrating the safety and feasibility in a phase I study, we conducted a phase II clinical study of CLAG (cladribine, cytarabine, granulocyte colony-stimulating factor) regimen combined with IM for patients with RR-AML. PATIENTS AND METHODS: We performed a single-institution 2-stage phase II study...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28960496/synthesis-and-functional-investigations-of-computer-designed-novel-cladribine-like-compounds-for-the-treatment-of-multiple-sclerosis
#9
Serkan Yavuz, Aysu Çetin, Atilla Akdemir, Doğukan Doyduk, Ali Dişli, Gurbet Çelik Turgut, Alaattin Şen, Yılmaz Yıldırır
Cladribine (2-CdA) is used as an anti-cancer drug but is currently studied as a potential treatment for use in relapsing-remitting multiple sclerosis (MS). In this study, we computer designed, synthesized, and characterized two novel derivatives of 2-CdA, K1-5d and K2-4c, and investigated their underlying mechanism of beneficial effect using the CCRF-CEM and RAJI cell lines. For this purpose, we first determined their effect on MS and DNA damage and repair-related gene expression profiles using custom arrays along with 2-CdA treatment at non-toxic doses...
September 28, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28915641/reevaluation-of-atr-signaling-in-primary-resting-chronic-lymphocytic-leukemia-cells-evidence-for-pro-survival-or-pro-apoptotic-function
#10
Maxime Beyaert, Eliza Starczewska, Ana Cristina González Pérez, Nicolas Vanlangendonck, Pascale Saussoy, Gaëlle Tilman, Anne De Leener, Marie-Christiane Vekemans, Eric Van Den Neste, Françoise Bontemps
ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress. By investigating the response of CLL cells to UV-C irradiation, a prototypical activator of ATR, we could detect phosphorylation of ATR at Thr-1989, a marker for ATR activation, and also observed that selective ATR inhibitors markedly decreased UV-C-induced phosphorylation of ATR targets, including H2AX and p53...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28884753/cladribine-an-old-newcomer-for-pulsed-immune-reconstitution-in-ms
#11
Heinz Wiendl
The EMA has approved cladribine tablets for the treatment of multiple sclerosis. The drug is not new, and the journey to its approval has been a long one, but the old concepts that cladribine therapy are based on provide a new option for the possibility of drug-free remission.
September 8, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28877978/how-i-manage-pulmonary-langerhans-cell-histiocytosis
#12
Gwenaël Lorillon, Abdellatif Tazi
Pulmonary Langerhans cell histiocytosis (PLCH) is a rare sporadic cystic lung disease of unknown aetiology that is characterised by the infiltration and destruction of the wall of distal bronchioles by CD1a(+) Langerhans-like cells. In adults, PLCH is frequently isolated and affects young smokers of both sexes. Recent multicentre studies have led to the more standardised management of patients in clinical practice. Smoking cessation is essential and is occasionally the only suitable intervention. Serial lung function testing is important because a significant proportion of patients may experience an early decline in forced expiratory volume in 1 s and develop airflow obstruction...
September 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28870107/safety-and-efficacy-of-cladribine-tablets-in-patients-with-relapsing-remitting-multiple-sclerosis-results-from-the-randomized-extension-trial-of-the-clarity-study
#13
Gavin Giovannoni, Per Soelberg Sorensen, Stuart Cook, Kottil Rammohan, Peter Rieckmann, Giancarlo Comi, Fernando Dangond, Abidemi K Adeniji, Patrick Vermersch
BACKGROUND: In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. METHODS: In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28859038/refractory-lch-with-secondary-intracranial-pnet-a-case-report-and-review-of-literature
#14
Varsha Chayapathi, Amita Mahajan, Manas Kalra
The occurrence of second malignant neoplasms in patients with Langerhans cell histiocytosis is infrequent but has been reported. Here we report the case of a child with refractory Langerhans cell histiocytosis who was treated with cladribine and later developed a secondary intracranial primitive neuroectodermal tumor. The possible association of cladribine with second neoplasm is further discussed.
August 30, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28858531/an-update-on-cladribine-for-relapsing-remitting-multiple-sclerosis
#15
Trygve Holmøy, Øivind Torkildsen, Kjell-Morten Myhr
Despite recent progress, currently available therapies for relapsing remitting multiple sclerosis (MS) are only partly effective, and their use is limited by tolerability and safety issues, as well as high cost. Cladribine was originally rejected by the regulatory authorities in both the European Union and USA in 2011, but in June 2017 the European Medical Agency recommended marketing authorization for treatment of aggressive relapsing MS. Areas covered: We provide an update on chemistry, mechanism of action, efficacy and safety of cladribine for the treatment of MS...
October 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28857680/cladribine-versus-fingolimod-natalizumab-and-interferon-%C3%AE-for-multiple-sclerosis
#16
Tomas Kalincik, Vilija Jokubaitis, Tim Spelman, Dana Horakova, Eva Havrdova, Maria Trojano, Jeannette Lechner-Scott, Alessandra Lugaresi, Alexandre Prat, Marc Girard, Pierre Duquette, Pierre Grammond, Claudio Solaro, Francois Grand'Maison, Raymond Hupperts, Julie Prevost, Patrizia Sola, Diana Ferraro, Murat Terzi, Ernest Butler, Mark Slee, Allan Kermode, Marzena Fabis-Pedrini, Pamela McCombe, Michael Barnett, Cameron Shaw, Suzanne Hodgkinson, Helmut Butzkueven
OBJECTIVE: This propensity score-matched analysis from MSBase compared the effectiveness of cladribine with interferon β, fingolimod or natalizumab. METHODS: We identified all patients with relapse-onset multiple sclerosis, exposure to the study therapies and ⩾1-year on-treatment follow-up from MSBase. Three pairwise propensity score-matched analyses compared treatment outcomes over 1 year. The outcomes were hazards of first relapse, disability accumulation and disability improvement events...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28817997/positive-impact-of-cladribine-on-quality-of-life-in-people-with-relapsing-multiple-sclerosis
#17
Dayo Afolabi, Christo Albor, Lukasz Zalewski, Dan R Altmann, David Baker, Klaus Schmierer
BACKGROUND: A number of elements of the pivotal 'cladribine tablets treating multiple sclerosis orally' (CLARITY) trial have remained unpublished. OBJECTIVE: To report the impact of cladribine on health-related quality of life (QoL) in people with relapsing multiple sclerosis (pwRMS). METHODS: QoL data from the phase III trial of two different doses (3.5 and 5.15 mg/kg) of oral cladribine in pwRMS were acquired from the European Medicines Agency through Freedom of Information...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28766548/-hairy-cell-leukemia-and-pregnancy
#18
L S Al-Radi, T N Moiseeva, S Yu Smirnova, R G Shmakov
The paper presents experience in following up and treating hairy cell leukemia (HCL) during pregnancy. The combination of HCL and pregnancy was observed in 5 patients. The patients' median age was 35 years (range, 28-42 years). The diagnosis of HCL was based on a conventional examination protocol: clinical blood analysis with the morphological assessment of lymphocytes, a myelogram and trepanobiopsy, immunophenotypic analysis of lymphocytes or bone marrow (in all the patients), cytochemical determination of tartrate-resistant acid phosphatase in 3 patients, and identification of BRAFV600E mutation in 3 patients...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28747289/retrospective-evaluation-of-hairy-cell-leukemia-patients-treated-with-three-different-first-line-treatment-modalities-in-the-last-two-decades-a-single-center-experience
#19
Şeniz Öngören, Ahmet Emre Eşkazan, Selin Berk, Tuğrul Elverdi, Ayşe Salihoğlu, Muhlis Cem Ar, Zafer Başlar, Yıldız Aydın, Nükhet Tüzüner, Teoman Soysal
OBJECTIVE: In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL) cases. MATERIALS AND METHODS: Sixty-six patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA) was administered in 31 cases, 19 patients received interferon-alpha (INF-α), splenectomy was performed in 16 cases, and rituximab was used in one. RESULTS: Although the highest overall response rate (ORR) was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups...
July 27, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28690524/erdheim-chester-disease-case-report-with-aggressive-multisystem-manifestations-and-review-of-the-literature
#20
Sultan Alotaibi, Osama Alhafi, Hatem Nasr, Khalid Eltayeb, Ghaleb Elyamany
Erdheim-Chester disease (ECD) is an extremely rare and aggressive form of non-Langerhans cell histiocytosis. ECD usually presents with bone pain in adults aged 40-60. Its etiology is unknown but it is thought to be either a reactive or neoplastic disorder. Recently, mutation of the proto-oncogene BRAF (BRAFV600E) has been found in more than 50% of cases. The multisystemic form of ECD is associated with significant morbidity, which may arise due to histiocytic infiltration of critical organ systems. The common sites of involvement are the skeleton, central nervous system, cardiovascular system, lungs, retroperitoneum, and skin...
May 2017: Case Reports in Oncology
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