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https://www.readbyqxmd.com/read/27913471/sequencing-of-chronic-lymphocytic-leukemia-therapies
#1
Jacqueline C Barrientos
It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in frontline, relapsed, refractory, and high-risk disease. Traditionally, frontline management of CLL has been a combination of chemotherapy (fludarabine, cyclophosphamide, bendamustine, or chlorambucil) with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab). The current landscape is rapidly evolving with the advent of therapies that demonstrate selective inhibition of important pathways necessary for CLL proliferation and survival...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27882024/outcomes-of-first-line-chemotherapy-in-patients-with-chronic-lymphocytic-leukemia
#2
Adil Nazir, Fawad, Sheeraz Ali, Farhana Badar, Neelam Siddique, Abdul Hameed
OBJECTIVE: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease in terms of survival with and without treatment. Many chemo and immunotherapeutic agents are available to treat this indolent disease. Aim of this study was to determine the outcomes of patients with chronic lymphocytic leukemia treated with different available chemotherapeutic regimens. METHODS: All patients with diagnosis of CLL from 2008 to 2013 were included. Data were collected from hospital information system...
September 2016: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/27878835/first-line-therapy-for-chronic-lymphocytic-leukemia-in-patients-older-than-79%C3%A2-years-is-feasible-and-achieves-good-results-a-filo-retrospective-study
#3
Godelieve Meunier, Loic Ysebaert, Phi Linh Nguyen-Thi, Stéphane Lepretre, Anne Quinquenel, Jehan Dupuis, Richard Lemal, Thérèse Aurran, Cécile Tomowiak, Florence Cymbalista, Marie Sarah Dilhuydy, Annie Brion, Pierre Morel, Bruno Cazin, Véronique Leblond, Guillaume Cartron, Daniel Ré, Marie Christine Béné, Anne Sophie Michallet, Pierre Feugier
The mean age at diagnosis of chronic lymphocytic leukemia (CLL) is 72 years, with 22.8% of patients being older than 80 years. However, the elderly are underrepresented in clinical studies of CLL. We performed a retrospective study of CLL patients aged 80 years or older at the initiation of first-line therapy in hospitals affiliated with the French intergroup on CLL (French Innovative Leukemia Organization) between 2003 and 2013. Here, we describe the clinical and biological characteristics, treatment, and outcomes for 201 patients...
November 22, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27862213/synthesis-and-preliminary-biological-evaluation-of-a-99m-tc-chlorambucil-derivative-as-a-potential-tumor-imaging-agent
#4
Jianguo Lin, Ling Qiu, Gaochao Lv, Ke Li, Wei Wang, Guiqing Liu, Xueyu Zhao, Shanshan Wang
Technetium-99 m-based radiopharmaceuticals have been used widely as diagnostic agents in the nuclear medicine. Chlorambucil (CLB) as one typical alkylating drug exhibits excellent inhibition effects against many human malignancies. In order to develop and explore a novel potential imaging agent for early diagnosis of tumors, tricarbonyl technetium-99 m and rhenium complexes based on the tridentate ligand dipicolylamine (DPA) bound to the chlorambucil pharmacophore were designed and synthesized: (99m) Tc-DPA-CLB (3) and Re-DPA-CLB (4)...
November 16, 2016: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27836498/repositioning-of-chlorambucil-as-a-potential-anti-schistosomal-agent
#5
Maha M Eissa, Shereen F Mossallam, Eglal I Amer, Layla K Younis, Hoda A Rashed
As parasites and cancer cells share many lifestyle and behavioral resemblances, repositioning of anti-cancerous agents as anti-parasitic is quite trendy, especially those sharing the same therapeutic targets. Therefore, the current study investigated the in vitro efficacy of ascending concentrations of chlorambucil (0.5-20μg/ml) against adult Schistosoma mansoni worms, over 72h. Additionally, its in vivo effects against the different developmental stages of the worm were assessed, after an oral dose of 2.5mg/kg/day for five successive days, through evaluating the worm load reduction and worms' morphological alterations and oogram changes...
November 9, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27823879/new-approach-of-delivering-cytotoxic-drugs-towards-caix-expressing-cells-a-concept-of-dual-target-drugs
#6
Simon J A van Kuijk, Nanda Kumar Parvathaneni, Raymon Niemans, Marike W van Gisbergen, Fabrizio Carta, Daniela Vullo, Silvia Pastorekova, Ala Yaromina, Claudiu T Supuran, Ludwig J Dubois, Jean-Yves Winum, Philippe Lambin
Carbonic anhydrase IX (CAIX) is a hypoxia-regulated and tumor-specific protein that maintains the pH balance of cells. Targeting CAIX might be a valuable approach for specific delivery of cytotoxic drugs, thereby reducing normal tissue side-effects. A series of dual-target compounds were designed and synthesized incorporating a sulfonamide, sulfamide, or sulfamate moiety combined with several different anti-cancer drugs, including the chemotherapeutic agents chlorambucil, tirapazamine, and temozolomide, two Ataxia Telangiectasia and Rad3-related protein inhibitors (ATRi), and the anti-diabetic biguanide agent phenformin...
October 19, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27812258/presentation-and-outcome-of-castleman-s-disease-in-immunocompetent-hosts
#7
Gaurav Prakash, Amanjeet Bal, Pankaj Malhotra, Vaishali Aggarwal, Alka Khadwal, Vikas Suri, Sanjay Jain, Savita Kumari, Radhika Srinivasan, Ashim Das, Neelam Varma, Subhash Varma
Castleman's disease (CD) is a heterogeneous lymphoproliferative disorder of unknown aetiology. Mostly, this disorder is seen in immunocompromised hosts. It is known to be associated with systemic disorders like HIV, HHV-8, lymphoma, and Kaposi sarcoma. As of today, the clinical behaviour and outcome of CD in immunocompetent host remains suboptimally studied. We analyzed consecutively treated cases of CD presented to our centre in last 12 years. Case record files were studied for patient's characteristics, clinical presentation, baseline laboratory and pathologic parameters, therapy and outcome...
December 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27796157/management-of-elderly-and-unfit-patients-with-chronic-lymphocytic-leukemia
#8
Francesca R Mauro, Adriano Salaroli, Maria D Caputo, Gioia Colafigli, Luigi Petrucci, Melissa Campanelli, Antonietta Ferretti, Anna R Guarini, Robin Foà
About 75% of patients with chronic lymphocytic leukemia (CLL) are more than 65 years at the time of diagnosis. Treatment of the elderly remains complicated due to multiple factors, such as comorbidities, decline in functional reserve and fitness. Since chronological age by itself cannot properly predict life expectancy and treatment tolerance, an accurate assessment of the fitness status is of crucial importance for an optimal treatment choice. Areas covered: This review will discuss the most relevant aspects concerning the issues experienced in the management of elderly/unfit patients with CLL...
December 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27767434/primary-nodal-hemangiosarcoma-in-four-dogs
#9
Catherine M Chan, Courtney H Zwahlen, Louis-Philippe de Lorimier, Stephen M Yeomans, Karon L Hoffmann, Antony S Moore
CASE DESCRIPTION 4 dogs with a slow-growing mass in the cervical region were evaluated. CLINICAL FINDINGS All dogs had no clinical signs at the time of the evaluation. There was no apparent evidence of visceral metastases or other primary tumor based on available CT or MRI data for any dog. TREATMENT AND OUTCOME For each dog, surgery to remove the mass was performed. Histologic examination of the excised tissue revealed a completely excised grade 1 or 2 lymph node hemangiosarcoma. All dogs received adjuvant chemotherapy; 2 dogs underwent curative intent chemotherapy, 1 dog underwent metronomic treatment with cyclophosphamide, and 1 dog underwent metronomic treatment with chlorambucil...
November 1, 2016: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/27754769/treatment-of-serpiginous-choroiditis-with-chlorambucil-a-report-of-17-patients
#10
Nazanin Ebrahimiadib, Bobeck S Modjtahedi, Samaneh Davoudi, C Stephen Foster
PURPOSE: To evaluate the efficacy of chlorambucil in the treatment of serpiginous choroiditis. METHODS: Patient records from the Massachusetts Eye Research and Surgery Institution (MERSI) were reviewed from over the past 10 years. In total, 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil were identified. QuantiFERON gold was negative in all of them. Chlorambucil was started at 0.15 mg/kg and dosage was titrated up using weekly white blood cell (WBC) count to achieve a target cell number of 3...
October 18, 2016: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/27754672/photocaging-of-single-and-dual-similar-or-different-carboxylic-and-amino-acids-by-acetyl-carbazole-and-its-application-as-dual-drug-delivery-in-cancer-therapy
#11
Yarra Venkatesh, Yetirajam Rajesh, Sambath Karthik, Chetan Anabur C, Mahitosh Mandal, Avijit Jana, N D Pradeep Singh
A new fluorescent photoremovable protecting group (FPRPG) based on acetylcarbazole framework has been explored for the first time release of single and dual (similar or different) substrates from single chromophore. Mechanistic studies of the photorelease process revealed that photorelease of two (similar or different) substrates from acetyl carbazole proceeds via a stepwise pathway. Further, we constructed photoresponsive dual drug delivery system (DDS) to release of two different anticancer drugs (Caffeic acid and Chlorambucil 1 equivalent each)...
October 18, 2016: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/27751969/coexistence-of-chronic-lymphocytic-leukemia-and-acute-myeloid-leukemia
#12
Ivana Milosevic
A 76-years old man presented with leucocytosis (86x109/l), fever, pneumonia and significant weight loss. He had a history of chronic lymphocytic leukemia diagnosed five years earlier and he responded with partial remission to the treatment with continuous low doses of chlorambucil. Analysis of blood smear, bone marrow aspiration and bone marrow biopsy revealed predomination of small lymphocytes, but 22% of cells were blasts negative to cytochemical stainings (Figure 1). Flow cytometric analysis showed two distinct populations: 65% of cells was small to moderate in size, CD19+, CD45+, CD5+, CD20+/-, but 30% of cells were large, CD34+, CD13+, HLA DR+, CD65+, CD45+, MPO weakly positive and CD33, CD14, CD15, CD16 negative...
October 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/27746042/rituximab-in-lymphoma-and-chronic-lymphocytic-leukaemia-a-practice-guideline
#13
A Prica, F Baldassarre, L K Hicks, K Imrie, T Kouroukis, M Cheung
Rituximab is the first monoclonal antibody to be approved for use by the US Food and Drug Administration in cancer. Its role in the treatment of non-Hodgkin lymphoma, including chronic lymphocytic leukaemia (CLL), has evolved significantly. We aimed to systematically review and update the literature on rituximab in lymphoma and CLL, and provide evidence-based consensus guidelines for its rational use. Validated methodology from the Cancer Care Ontario Program in Evidence-based Care was used. A comprehensive literature search was completed by a methodologist from the Hematology Disease Site Group of Cancer Care Ontario...
October 13, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/27706928/three-arm-biotin-tagged-carbazole-dicyanovinyl-chlorambucil-conjugate-simultaneous-tumor-targetting-sensing-and-photoresponsive-anticancer-drug-delivery
#14
Pradeep Singh, Yarra Venkatesh, S Karthik, Y Rajesh, Mahitosh Mandal, Avijit Jana
Here we report the design, synthesis and in vitro biological studies of a Biotin-Carbazole-Dicyanovinyl-Chlorambucil conjugate (Bio-CBZ-DCV-CBL). This conjugate (6) is a multifunctional single molecule appliance composed of thiol-sensor Dicyanovinyl functionality, a Carbazole derived phototrigger and the fluorescent reporter, chlorambucil (CBL) as the anticancer drug, and biotin as the cancer-targeting ligand. In conjugate 6, the dicyanovinyl bond undergoes thiol-ene click reaction at pH< 7 with intracellular thiols thereby shuttingdown the internal charge transfer between donor carbazole and acceptor dicyanovinyl unit results in change of fluorescence color from green to blue and thereby sense the tumor microenvironment, followed by photoirradiation results in release of the anticancer drug CBL in controlled manner...
October 5, 2016: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/27703384/economic-evaluation-of-obinutuzumab-in-combination-with-chlorambucil-in-first-line-treatment-of-patients-with-chronic-lymphocytic-leukemia-in-spain
#15
Luis Felipe Casado, Amparo Burgos, Eva González-Haba, Javier Loscertales, Tania Krivasi, Javier Orofino, Carlos Rubio-Terres, Darío Rubio-Rodríguez
OBJECTIVE: To evaluate the cost-effectiveness of obinutuzumab in combination with chlorambucil (GClb) versus rituximab plus chlorambucil (RClb) in the treatment of adults with previously untreated chronic lymphocytic leukemia (CLL) and with comorbidities that make them unsuitable for full-dose fludarabine-based therapy, from the perspective of the Spanish National Health System. METHODS: A Markov model was developed with three mutually exclusive health states: progression-free survival (with or without treatment), progression, and death...
2016: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/27683974/cross-resistance-and-synergy-with-bendamustine-in-chronic-lymphocytic-leukemia
#16
Sara E F Kost, Eric D J Bouchard, Élise LaBossière, Xibiao Ye, Michelle L Queau, William S Liang, Versha Banerji, Spencer B Gibson, Sachin Katyal, James B Johnston
Bendamustine (BEN) has structural similarities to an alkylating agent and a nucleoside analog, and effective against tumor cells that are resistant to standard therapy. In this study we compared the activities of BEN against that of the alkylating agent, chlorambucil (CLB), and the nucleoside analogs, fludarabine (FLU) and deoxyadenosine/pentostatin (dADO/PEN), in primary chronic lymphocytic leukemia (CLL) cells in vitro. Cross-resistance was observed between BEN, CLB and FLU, with previously treated patients or those with a deletion 17p being most resistant...
September 20, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27660471/novel-chlorambucil-conjugated-anionic-linear-globular-peg-based-second-generation-dendrimer-in-vitro-in-vivo-improved-anticancer-activity
#17
Artin Assadi, Vahideh Sharifi Najafabadi, Seyed Ataollah Sadat Shandiz, Azadah Shayeq Boroujeni, Sepehr Ashrafi, Ali Zaman Vaziri, Seyedeh Masoumeh Ghoreishi, Mohammad Reza Aghasadeghi, Seyed Esmaeil Sadat Ebrahimi, Morteza Pirali-Hamedani, Mehdi Shafiee Ardestani
Evaluating the efficacy of anticancer drugs is an evolving and research-oriented issue. The objective of this study was to reduce the insolubility of chlorambucil (CBL) in water and improve the anticancer activity of CBL in vitro and in vivo through the conjugation of CBL with anionic linear-globular dendrimer (second generation, G2). In the current study, the anticancer activity among three groups that include CBL, CBL-G2 dendrimer, and control was measured in vitro and in vivo. In vitro studies showed that G2 anionic linear-globular polyethylene-glycol-based dendrimer, which conjugated to the CBL exterior through an ester linkage, was able to significantly improve the treatment efficacy over clinical CBL alone with respect to proliferation assay, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide; half maximal inhibitory concentration (IC50) was calculated to be 141 µg/mL for CBL alone and 27...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27630351/lymphoma-of-the-cervix-case-report-and-review-of-the-literature
#18
Ziad Hilal, Franziska Hartmann, Askin Dogan, Cem Cetin, Harald Krentel, Sven Schiermeier, Beate Schultheis, Clemens B Tempfer
BACKGROUND: Lymphoma of the uterine cervix (LUCX) is rare and may occur as a primary or secondary manifestation of this disease. Clinical and cytological presentations of LUCX vary and establishing diagnosis is often difficult. Surgery followed by radiation or chemotherapy is the mainstay of treatment. CASE REPORT: We present the case of a 73-year-old woman with recurrent pathological PAP smears of the cervix and a history of chronic lymphatic leukemia 15 years ago...
September 2016: Anticancer Research
https://www.readbyqxmd.com/read/27603417/responsive-prodrug-self-assembled-vesicles-for-targeted-chemotherapy-in-combination-with-intracellular-imaging
#19
Hongzhong Chen, Huijun Phoebe Tham, Chung Yen Ang, Qiuyu Qu, Lingzhi Zhao, Pengyao Xing, Linyi Bai, Si Yu Tan, Yanli Zhao
Targeted drug delivery systems having controlled drug release property with an inherent fluorescence reporter have drawn a lot of attention in nanomedicine. However, only very few prodrugs can be directly used to construct such delivery systems. Herein, we report that an amphiphilic chlorambucil-based prodrug consisting of a fluorescence reporter and a d-mannose targeting ligand could directly self-assemble into glutathione-responsive nanovesicles for selective cancer therapy and intracellular imaging. These nanovesicles could be dissociated to release the chlorambucil drug with obviously red-shifted fluorescence when internalized by d-mannose receptor-overexpressed MCF-7 cancer cells...
September 21, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27564097/differential-effects-of-histone-deacetylase-inhibitors-on-cellular-drug-transporters-and-their-implications-for-using-epigenetic-modifiers-in-combination-chemotherapy
#20
Benigno C Valdez, Yang Li, David Murray, Jonathan E Brammer, Yan Liu, Chitra Hosing, Yago Nieto, Richard E Champlin, Borje S Andersson
HDAC inhibitors, DNA alkylators and nucleoside analogs are effective components of combination chemotherapy. To determine a possible mechanism of their synergism, we analyzed the effects of HDAC inhibitors on the expression of drug transporters which export DNA alkylators. Exposure of PEER lymphoma T-cells to 15 nM romidepsin (Rom) resulted in 40%-50% reduction in mRNA for the drug transporter MRP1 and up to ~500-fold increase in the MDR1 mRNA within 32-48 hrs. MRP1 protein levels concomitantly decreased while MDR1 increased...
August 24, 2016: Oncotarget
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