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Cladribine

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
September 11, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28857680/cladribine-versus-fingolimod-natalizumab-and-interferon-%C3%AE-for-multiple-sclerosis
#7
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
#8
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
#9
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-3-different-first-line-treatment-modalities-in-the-last-two-decades-a-single-center-experience
#10
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 analysed the clinical outcome, treatment responses, infectious complications and survival rates of seventy-one 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 thirty-one, nineteen 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 upfront 2-CdA, ORRs were comparable in 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
#11
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
https://www.readbyqxmd.com/read/28664935/mutually-exclusive-recurrent-kras-and-map2k1-mutations-in-rosai-dorfman-disease
#12
Sofia Garces, L Jeffrey Medeiros, Keyur P Patel, Shaoying Li, Sergio Pina-Oviedo, Jingyi Li, Juan C Garces, Joseph D Khoury, C Cameron Yin
Rosai-Dorfman disease is a histiocytic disorder with a poorly defined pathogenesis. Recent molecular studies have revealed recurrent mutations involving genes in the MAPK/ERK pathway in Langerhans cell histiocytosis and Erdheim-Chester disease. However, cases of Rosai-Dorfman disease have rarely been assessed. We performed next-generation sequencing to assess 134 genes on 21 cases of Rosai-Dorfman disease, including 13 women and 8 men with a median age of 43 years (range, 3-82). In all, 13 had extranodal, 5 had nodal, and 3 had coexistent nodal and extranodal disease...
June 30, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28626781/both-cladribine-and-alemtuzumab-may-effect-ms-via-b-cell-depletion
#13
David Baker, Samuel S Herrod, Cesar Alvarez-Gonzalez, Lukasz Zalewski, Christo Albor, Klaus Schmierer
OBJECTIVE: To understand the efficacy of cladribine (CLAD) treatment in MS through analysis of lymphocyte subsets collected, but not reported, in the pivotal phase III trials of cladribine and alemtuzumab induction therapies. METHODS: The regulatory submissions of the CLAD Tablets Treating Multiple Sclerosis Orally (CLARITY) (NCT00213135) cladribine and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, study one (CARE-MS I) (NCT00530348) alemtuzumab trials were obtained from the European Medicine Agency through Freedom of Information requests...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28624910/clinical-pharmacology-and-clinical-trials-of-ribonucleotide-reductase-inhibitors-is-it-a-viable-cancer-therapy
#14
REVIEW
Mukundan Baskar Mannargudi, Subrata Deb
PURPOSE: Ribonucleotide reductase (RR) enzymes (RR1 and RR2) play an important role in the reduction of ribonucleotides to deoxyribonucleotides which is involved in DNA replication and repair. Augmented RR activity has been ascribed to uncontrolled cell growth and tumorigenic transformation. METHODS: This review mainly focuses on several biological and chemical RR inhibitors (e.g., siRNA, GTI-2040, GTI-2501, triapine, gemcitabine, and clofarabine) that have been evaluated in clinical trials with promising anticancer activity from 1960's till 2016...
August 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28599315/reevaluation-of-atr-signaling-in-primary-resting-chronic-lymphocytic-leukemia-cells-evidence-for-pro-survival-or-pro-apoptotic-function
#15
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...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596664/bullous-pyoderma-gangrenosum-associated-with-hairy-cell-leukemia-and-its-complete-response-to-cladribine-therapy
#16
Ankur Jain, Deepesh Lad, Gaurav Prakash, Alka Khadwal, Pankaj Malhotra, Amanjit Bal, Nabhajit Mallik, Narendar Kumar, Subhash Varma
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis seen in association with systemic disorders including hematologic malignancies. Hairy cell leukemia (HCL) however, is an unusual association of PG. We describe a 49-year old lady who presented to our hematology clinic with easy fatiguability and ulcerative skin lesions of 6 months duration. Examination revealed pallor and massive splenomegaly. Indurated, ulcerated lesion with undermined edges and necrotic base was observed on left thigh. Investigations revealed pancytopenia and bone marrow examination identified typical hairy cells...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28553668/the-clinical-spectrum-of-erdheim-chester-disease-an-observational-cohort-study
#17
Juvianee I Estrada-Veras, Kevin J O'Brien, Louisa C Boyd, Rahul H Dave, Benjamin Durham, Liqiang Xi, Ashkan A Malayeri, Marcus Y Chen, Pamela J Gardner, Jhonell R Alvarado-Enriquez, Nikeith Shah, Omar Abdel-Wahab, Bernadette R Gochuico, Mark Raffeld, Elaine S Jaffe, William A Gahl
Erdheim-Chester Disease (ECD) is a rare, potentially fatal, multi-organ myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a-, and frequently S100-. The purpose of this report is to describe the clinical and molecular variability of ECD. Sixty consecutive ECD patients (45 males, 15 females) were prospectively evaluated at the NIH Clinical Center between 2011 and 2015. Comprehensive imaging and laboratory studies were performed, and tissues were examined for BRAF V600E and MAPK pathway mutations...
February 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/28544144/cladribine-is-a-promising-therapy-for-xanthoma-disseminatum
#18
E Adışen, P Aladağ, E Özlem, M A Gürer
No abstract text is available yet for this article.
May 22, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28539531/synergistic-activity-of-an-antimetabolite-drug-and-tyrosine-kinase-inhibitors-against-breast-cancer-cells
#19
Yushan Wu, Dongxing Zhang, Baofan Wu, Yuan Quan, Dongwu Liu, Yanyan Li, Xiuzhen Zhang
Antimetabolite drugs, including the adenosine deaminase inhibitor cladribine, have been shown to induce apoptosis in a variety of cancer cells, and have been widely used in clinical trials of various cancers in conjunction with tyrosine kinase inhibitors (TKIs). Combination treatment with cladribine and gefitinib or dasatinib is expected to have a synergistic inhibitory effect on breast cancer cell growth. Our results demonstrated that the combination treatment had synergistic activity against human breast cancer (MCF-7) cells, enhanced G2/M cell arrest and reactive oxygen species (ROS) generation, and increased the loss of mitochondrial membrane potential and cell apoptosis...
August 1, 2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28523957/clinical-case-idelalisib-induced-immunoglobulin-flare
#20
Jan Novak, Martin Havrda, Lubica Gaherova, Jan Spicka, Tomas Kozak
IgM flare is a transient, treatment-induced, increase of monoclonal IgM levels in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) patients. Until recently this phenomenon was observed in patients treated with Cladribine and Rituximab. Here we report a case of a heavily pretreated chronic lymphocytic leukemia patient with an atypically high immunoglobulin production who developed clinically significant immunoglobulin flare following Idelalisib treatment.
August 2017: Immunopharmacology and Immunotoxicology
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