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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
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
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
Mouhamad Nasser, Julie Traclet, Vincent Cottin
Cladribine therapy may be beneficial in advanced forms of pulmonary Langerhans cell histiocytosis, even that with multiple cystic changes
January 2018: ERJ Open Research
(no author information available yet)
In the UK, there are twelve disease-modifying drugs licensed for various forms of multiple sclerosis (MS), of which three are oral therapies. An oral formulation of cladribine (Mavenclad - Merck Serono Europe Limited) was recently licensed by the European Medicines Agency (EMA) for the treatment of adult patients with highly active relapsing MS.1,2 It is claimed to be "an innovatively simple approach" for treating this form of MS and "the only disease modifying therapy that can deliver and sustain 4 years of disease control with a maximum of 20 days oral treatment in the first 2 years...
February 2018: Drug and Therapeutics Bulletin
Tadeusz Robak, Jerzy Blonski, Aleksander Bartłomiej Skotnicki, Magdalena Piotrowska, Tomasz Wróbel, Justyna Rybka, Janusz Kłoczko, Łukasz Bołkun, Bożena Katarzyna Budziszewska, Urszula Walczak, Anatoly Uss, Marta Fidecka, Piotr Smolewski
OBJECTIVES: PALG CLL4 is the first, randomized, phase IIIb study with cladribine, cyclophosphamide and rituximab (RCC) induction and subsequent maintenance with rituximab in previously untreated chronic lymphocytic leukemia (CLL) patients. METHODS: The induction treatment consisted of six RCC cycles regimen. Patients with complete response (CR) or partial response (PR) after an induction phase were randomized into a maintenance arm with rituximab or an observational arm...
February 10, 2018: European Journal of Haematology
J Zhang, Y Sun, X Zhang, B Long, Y Lu, X Li
This report preliminarily evaluates the efficacy and safety of cladribine, cytarabine, mitoxantrone, and granulocyte colony-stimulating factor (CLAG-M) as bridging therapy to myeloablative allogeneic hematopoietic cell transplantation (allo-HCT) in the treatment of patients with refractory or relapsed acute myeloid leukemia. Five patients with high-risk refractory or relapsed acute myeloid leukemia received the CLAG-M regimen and subsequent bridging to myeloablative allo-HCT between December 2014 and August 2015 in our hospital...
January 2018: Transplantation Proceedings
Giancarlo Comi, Stuart Cook, Kottil Rammohan, Per Soelberg Sorensen, Patrick Vermersch, Abidemi K Adeniji, Fernando Dangond, Gavin Giovannoni
Background: The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Methods: Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3...
2018: Therapeutic Advances in Neurological Disorders
D J Inwards, P A Fishkin, B R LaPlant, M T Drake, P J Kurtin, D A Nikcevich, D B Wender, B S Lair, T E Witzig
No abstract text is available yet for this article.
January 29, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Haydar Çelik, Marika Sciandra, Bess Flashner, Elif Gelmez, Neslihan Kayraklıoğlu, David V Allegakoen, Jeff R Petro, Erin J Conn, Sarah Hour, Jenny Han, Lalehan Oktay, Purushottam B Tiwari, Mutlu Hayran, Brent T Harris, Maria Cristina Manara, Jeffrey A Toretsky, Katia Scotlandi, Aykut Üren
Ewing sarcoma (ES) is an aggressive bone and soft tissue malignancy that predominantly affects children and adolescents. CD99 is a cell surface protein that is highly expressed on ES cells and is required to maintain their malignancy. We screened small molecule libraries for binding to extracellular domain of recombinant CD99 and subsequent inhibition of ES cell growth. We identified two structurally similar FDA-approved compounds, clofarabine and cladribine that selectively inhibited the growth of ES cells in a panel of 14 ES vs...
January 31, 2018: Oncogene
Kate T Carroll, Bryson C Lochte, James Y Chen, Vivian S Snyder, Bob S Carter, Clark C Chen
Magnetic resonance imaging (MRI)-guided biopsy is an emerging diagnostic technique that holds great promise for otherwise difficult to access neuroanatomy. Here we describe MRI-guided biopsy of a suprasellar lesion located posterior and superior to the pituitary stalk. The approach was successfully implemented in a 38-year-old woman who had developed progressive visual deterioration. Intra-operative MRI revealed the need for trajectory adjustment due to an unintended, minor deviation in the burr hole entry point, demonstrating the benefit of an MRI-guided approach...
January 6, 2018: World Neurosurgery
Anamarija M Perry, Kant Matsuda, Vikram Wadhwa, Donna Hewitt, Muhamad Almiski, James B Johnston, Versha Banerji
Brain involvement, although rare, can occur in HCL.The combination of cladribine and rituximab is a highly effective treatment of HCL with brain involvement.
June 13, 2017: Blood Advances
Nathan D Seligson, Athena L V Hobbs, Joanna M Leonard, Elizabeth L Mills, Amy G Evans, Salil Goorha
BACKGROUND: Treatment for acute myeloid leukemia (AML) has remained relatively unchanged over the past few decades. Although recent drug approvals have provided an increase in the number of treatment options in AML, further optimization of standard induction therapy is still necessary. The most commonly utilized induction options have been well studied, but there is a paucity of literature comparing the combination of idarubicin with cytarabine and cladribine. OBJECTIVE: To assess the clinical effectiveness of the addition of cladribine to idarubicin and cytarabine (7+3 IA) induction therapy in the treatment of AML...
December 1, 2017: Annals of Pharmacotherapy
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-seven 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...
December 1, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Tamim Alsuliman, Kaiss Lassoued, Maifa Belghoul, Karima Debbache, Bachra Choufi
INTRODUCTION: Pentostatin (2'-deoxycoformycin) and cladribine (2-chlorodeoxyadenosine) are adenosine analogues widely used to treat lymphoid malignancies, mainly hairy cell leukemia (HCL). Oral or parenteral adenosine analogues have been also used as immunomodulatory agents in multiple sclerosis and in acute graft-versus-host disease. CASE REPORT: Here, we report the case of a 43-year-old patient with a history of extensive psoriasis who later developed HCL. RESULTS: The patient had achieved complete remission of both psoriasis and HCL after receiving intravenous infusions of pentostatin...
March 2018: Dermatology and Therapy
Y Bao, J Zhao, Z-Z Li
PURPOSE: To compare the clinical remission and survival between CLAG and FLAG induction chemotherapy in treating patients with refractory or relapsed acute myeloid leukemia (R/R AML). METHODS: 103 R/R AML patients were consecutively enrolled in this prospective cohort study. 55 patients were treated by CLAG induction chemotherapy as follows: 5 mg/m2 /day cladribine (days 1-5); 2 g/m2 /day cytarabine (days 1-5) and 300 μg/day filgrastim (days 0-5). While 48 patients were treated by FLAG: 30 mg/m2 /day fludarabine (days 1-5), 2 g/m2 /day cytarabine (days 1-5), and 300 μg/day filgrastim (days 0-5)...
November 27, 2017: Clinical & Translational Oncology
Gavin Giovannoni
Cladribine is a purine nucleoside analogue that selectively depletes peripheral lymphocytes without a major impact on cells of the innate immune system. An oral formulation of cladribine has been developed to be given as short courses over two annual cycles. Oral cladribine results in the peripheral depletion of lymphocytes that is gradual, occurring over several weeks, and is not associated with a cell lysis syndrome, has a greater impact on B cells than T cells, and is followed by gradual reconstitution of the peripheral lymphocyte counts over several months...
October 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Mohd Kashif Siddiqui, Inderpreet Singh Khurana, Sangeeta Budhia, Robert Hettle, Gerard Harty, Schiffon 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 28, 2017: Current Medical Research and Opinion
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
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...
January 2018: Clinical Lymphoma, Myeloma & Leukemia
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