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https://www.readbyqxmd.com/read/29222306/therapy-of-primary-cns-lymphoma-role-of-intensity-radiation-and-novel-agents
#1
REVIEW
Andrés José María Ferreri
Primary central nervous system (CNS) lymphomas represent a subgroup of malignancies with specific characteristics, an aggressive course, and unsatisfactory outcome in contrast with other lymphomas comparable for tumor burden and histological type. Despite the high sensitivity to conventional chemotherapy and radiotherapy, remissions are frequently short lasting. Treatment efficacy is limited by several factors, including the biology and microenvironment of this malignancy and the "protective" effect of the blood-brain barrier, which limits the access of most drugs to the CNS...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222271/optimizing-therapy-for-mantle-cell-lymphoma
#2
REVIEW
Peter Martin
Most people with mantle cell lymphoma (MCL) present with diffuse adenopathy and benefit from early initiation of rituximab and high-dose cytarabine- or bendamustine-based therapies. Some patients, however, present with primarily nonnodal disease that can follow either an indolent or a rapidly progressive, treatment-resistant clinical course. Rarely, patients present with explosive disease that can be challenging to manage and often involves the central nervous system. New agents with improved therapeutic indices facilitate treatment while maintaining quality of life, but also present new complications at the time of treatment failure...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222237/the-role-of-targeted-therapy-in-the-management-of-patients-with-aml
#3
REVIEW
Alexander E Perl
Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration's approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29218851/clinical-experience-with-the-bcl2-inhibitor-venetoclax-in-combination-therapy-for-relapsed-and-refractory-acute-myeloid-leukemia-and-related-myeloid-malignancies
#4
Courtney D DiNardo, Caitlin R Rausch, Christopher Benton, Tapan Kadia, Nitin Jain, Naveen Pemmaraju, Naval Daver, Wendy Covert, Kayleigh R Marx, Morgan Mace, Elias Jabbour, Jorge Cortes, Guillermo Garcia-Manero, Farhad Ravandi, Kapil N Bhalla, Hagop Kantarjian, Marina Konopleva
INTRODUCTION: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML) and efficacy in lower-intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported. METHODS: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed...
December 8, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29217775/chemotherapy-induced-differential-cell-cycle-arrest-in-b-cell-lymphomas-affects-their-sensitivity-to-wee1-inhibition
#5
Xiaoguang Wang, Zhangguo Chen, Ameet K Mishra, Alexa Silva, Wenhua Ren, Zenggang Pan, Jing H Wang
Chemotherapeutic agents, e.g., cytarabine or doxorubicin cause DNA damages. However, it remains unknown whether such agents differentially regulate cell cycle arrest in distinct types of B cell lymphomas, and whether this phenotype can be exploited for developing new therapies. Here, we treated various types of B cells including primary and B lymphoma cells, with cytarabine or doxorubicin, and determined DNA damage responses, cell cycle regulation and sensitivity to Wee1 inhibitor. We found that cyclin A2/B1 upregulation appear to be an intrinsic programmed response to DNA damage; however, different types of B cells arrest in distinct phases of cell cycle...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29214694/myelodysplastic-syndromes-2018-update-on-diagnosis-risk-stratification-and-management
#6
Guillermo Montalban-Bravo, Guillermo Garcia-Manero
DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis...
January 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29212978/-acute-myeloid-leukemia-complicated-by-pneumonia-and-vertebral-osteomyelitis-during-induction-chemotherapy
#7
Yuki Kamata, Yuki Fujiwara, Kentaro Mizuhara, Naoya Mochizuki, Shiro Kubonishi, Yasushi Hiramatsu
A 76-year-old woman was operated on for rectal cancer in 2011 without chemotherapy and was followed up in the outpatient department. Decrease in white blood cell count was observed from 2013, and she developed anemia in 2015. Bone marrow aspiration was performed, and she was diagnosed with acute myeloid leukemia with myelodysplasia-related changes (AML/MRC). First, remission induction therapy was initiated with idarubicin and cytarabine administration, but pneumonia and vertebral osteomyelitis developed during the neutropenic period...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29212418/clinical-characteristics-and-outcome-of-childhood-acute-promyelocitic-leukemia-apl-in-saudi-arabia-a-multicenter-saphos-leukemia-group-study
#8
Wasil Jastaniah, Abdulrahman Alsultan, Saad Al Daama, Walid Ballourah, Mohamed Bayoumy, Faisal Al-Anzi, Omar Al Shareef, Mohammed Burhan Abrar, Reem Al Sudairy, Ibrahim Al Ghemlas
BACKGROUND: Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival rates exceed 80% in developed countries. Successful treatments rely on all-trans retinoic acid with anthracycline-based chemotherapy. Availability of modern care and public knowledge play important roles in pediatric APL survival. METHOD: A cytogenetic diagnosis of APL was confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo AML between January 2005 and December 2012 at nine cancer care centers in Saudi Arabia...
December 7, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29212250/histone-deacetylase-inhibitors-reduce-differentiating-osteoblast-mediated-protection-of-acute-myeloid-leukemia-cells-from-cytarabine
#9
Rosalie M Sterner, Kimberly N Kremer, Aref Al-Kali, Mrinal M Patnaik, Naseema Gangat, Mark R Litzow, Scott H Kaufmann, Jennifer J Westendorf, Andre J van Wijnen, Karen E Hedin
The bone marrow microenvironment protects acute myeloid leukemia (AML) cells during chemotherapy and is a major factor in relapse. Here, we examined which type(s) of bone marrow cells are responsible for the relapse of AML following treatment with cytarabine (Ara-C), and we identified a means to inhibit this protection. To determine the protective cell type(s), AML cells were treated with Ara-C, and AML cell survival in the presence or absence of osteoblast lineage cells was assessed. Cultured AML cells and patient bone marrow isolates were each significantly protected from Ara-C-induced apoptosis by co-culture with differentiating osteoblasts...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29208403/efficacy-of-standard-dose-r-chop-alternating-with-r-hdac-followed-by-autologous-hematopoietic-cell-transplantation-as-initial-therapy-of-mantle-cell-lymphoma-a%C3%A2-single-institution-experience
#10
Yazeed Sawalha, Brian T Hill, Lisa A Rybicki, Danyu Sun, Robert M Dean, Deepa Jagadeesh, Betty K Hamilton, Aaron T Gerds, Ronald M Sobecks, Steven Andresen, Hien K Liu, Navneet S Majhail, Brad Pohlman, Matt E Kalaycio, Brian J Bolwell, Mitchell R Smith
BACKGROUND: Young fit patients with mantle cell lymphoma (MCL) are commonly treated with induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT). Induction regimens with modifications of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and/or incorporation of high-dose cytarabine (HDAC) appear more effective than R-CHOP alone. PATIENTS AND METHODS: We adopted a modification of the Nordic protocol using standard, rather than higher dose R-CHOP, alternating with HDAC (rituximab plus HDAC), for 3 cycles each or, for patients already treated with R-CHOP alone before referral for AHCT, an additional 2 cycles of rituximab plus HDAC...
December 2, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29199519/outcomes-of-da-epoch-r-induction-plus-autologous-transplant-consolidation-for-double-hit-lymphoma
#11
Andy I Chen, Jessica T Leonard, Craig Y Okada, Nathan D Gay, Kari Chansky, Guang Fan, Jennifer B Dunlap, Philipp W Raess, Rita M Braziel, Alex Stentz, Richard T Maziarz
High-grade B cell lymphoma with MYC and BCL2 rearrangements (double hit) has a poor prognosis with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). We report here a treatment algorithm of DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) followed by BEAM (carmustine, etoposide, cytarabine, melphalan) autologous transplant in 36 cases of previously untreated double hit lymphoma (DHL) from 2010 to 2015. A high risk International Prognostic Index (IPI) was present in 42% of cases...
December 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29193019/prospective-subgroup-analyses-of-the-randomized-mcl-002-sprint-study-lenalidomide-versus-investigator-s-choice-in-relapsed-or-refractory-mantle-cell-lymphoma
#12
Luca Arcaini, Thierry Lamy, Jan Walewski, David Belada, Jiri Mayer, John Radford, Wojciech Jurczak, Franck Morschhauser, Julia Alexeeva, Simon Rule, José Cabeçadas, Elias Campo, Stefano A Pileri, Tsvetan Biyukov, Meera Patturajan, Marie-Laure Casadebaig Bravo, Marek Trnĕný
In the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated significantly improved median progression-free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long-term follow-up data and results of preplanned subgroup exploratory analyses from MCL-002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL-002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1-21; 28-day cycles) or single-agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine)...
November 28, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29189507/acute-myeloid-leukemia-with-central-nervous-system-involvement-in-children-experience-from-the-french-protocol-analysis-elam02
#13
Arthur Felix, Thierry Leblanc, Arnaud Petit, Brigitte Nelkem, Yves Bertrand, Virginie Gandemer, Anne Sirvent, Catherine Paillard, Claudine Schmitt, Pierre Simon Rohrlich, Odile Fenneteau, Christine Ragu, Gerard Michel, Anne Auvrignon, André Baruchel, Guy Leverger
Central nervous system (CNS) involvement at diagnosis of pediatric acute myeloid leukemia (AML) is not considered as an independent prognostic factor. This study describes the prognostic value of pediatric AML with CNS involvement at diagnosis. Pediatric patients were treated for de novo AML in the French multicenter trial ELAM02. Lumbar puncture was carried out in the first week, and the treatment was adapted to the CNS status. No patient received CNS radiotherapy. The patients were classified into 2 groups: CNS+ and CNS-...
November 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29181696/comparison-of-clinical-remission-and-survival-between-clag-and-flag-induction-chemotherapy-in-patients-with-refractory-or-relapsed-acute-myeloid-leukemia-a-prospective-cohort-study
#14
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
https://www.readbyqxmd.com/read/29179468/pharmacometabolomics-identifies-dodecanamide-and-leukotriene-b4-dimethylamide-as-a-predictor-of-chemosensitivity-for-patients-with-acute-myeloid-leukemia-treated-with-cytarabine-and-anthracycline
#15
Guangguo Tan, Bingbing Zhao, Yanqing Li, Xi Liu, Zhilan Zou, Jun Wan, Ye Yao, Hong Xiong, Yanyu Wang
Clinical responses to standard cytarabine plus anthracycline regimen in acute myeloid leukemia (AML) are heterogeneous and there is an unmet need for biological predictors of response to this regimen. Here, we applied a pharmacometabolomics approach to identify potential biomarkers associated with response to this regimen in AML patients. Based on clinical response the enrolled 82 patients were subdivided into two groups: complete remission(CR) responders (n=42) and non-responders (n=40). Metabolic profiles of pre-treatment serum from patients were analyzed by ultra-high performance liquid chromatography coupled with mass spectrometry and the metabolic differences between the two groups were investigated by multivariate statistical analysis...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29175378/increased-activity-of-both-cdk1-and-cdk2-is-necessary-for-the-combinatorial-activity-of-wee1-inhibition-and-cytarabine
#16
Tamara B Garcia, Susan P Fosmire, Christopher C Porter
Inhibition of WEE1 is emerging as a promising chemosensitization strategy in many cancers including acute leukemia. Our lab and others have demonstrated that a small-molecule inhibitor of WEE1, AZD1775, sensitizes acute leukemia cells to cytarabine; however, a mechanism of combinatorial activity has remained elusive. Thus, we sought to determine the relative contribution of WEE1 targets CDK1 and CDK2 to the combinatorial activity of AZD1775 and cytarabine. To accomplish this, we expressed "WEE1 resistant" CDK1 (CDK1-AF) and CDK2 (CDK2-AF) constructs in a T-ALL cell line...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29174536/monophosphorylation-by-deoxycytidine-kinase-affects-apparent-cellular-uptake-of-decitabine-in-hct116-colon-cancer-cells
#17
Kumiko Ueda, Ayasa Masuda, Misaki Fukuda, Shota Tanaka, Mika Hosokawa, Seigo Iwakawa
Decitabine (DAC), a nucleoside-related DNA methylation inhibitor, is taken up into cancer cells via equilibrative nucleoside transporter 1 (ENT1), and is then monophosphorylated by deoxycytidine kinase (dCK). In the present study, we examined the contribution of dCK to the uptake of DAC in HCT116 colon cancer cells. Irinotecan and etoposide inhibited the uptake of [3H]-uridine and [3H]-DAC at 10 s and 5 min, while cytarabine and gemcitabine only inhibited that of [3H]-DAC at 5 min. Irinotecan and etoposide inhibited [3H]-DAC uptake in negative control small interfering RNA (siRNA)- or dCK siRNA-transfected cells at 10 s, whereas cytarabine and gemcitabine did not...
October 10, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29172076/gemtuzumab-ozogamicin-go-inclusion-to-induction-chemotherapy-eliminates-leukemic-initiating-cells-and-significantly-improves-survival-in-mouse-models-of-acute-myeloid-leukemia
#18
Cathy C Zhang, Zhengming Yan, Bernadette Pascual, Amy Jackson-Fisher, Donghui Stephen Huang, Qing Zong, Mark Elliott, Conglin Fan, Nanni Huser, Joseph Lee, Matthew Sung, Puja Sapra
Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML). Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs)...
November 21, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29167924/persistent-cytarabine-and-daunorubicin-exposure-after-administration-of-novel-liposomal-formulation-cpx-351-population-pharmacokinetic-assessment
#19
Mina Nikanjam, Edmund V Capparelli, Jeffrey E Lancet, Arthur Louie, Gary Schiller
PURPOSE: CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin which has recently been FDA approved for treatment of acute myeloid leukemia (AML). The current study investigated the pharmacokinetics (PK) of this liposomal formulation. METHODS: CPX-351 PK data (cytarabine, daunorubicin, and metabolites) from a phase I study of relapsed and refractory AML were used for the analysis. Therapy was given days 1, 3, and 5 of induction (3-134 units/m(2))...
November 22, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29164635/influence-of-genetic-variants-of-idh1-idh2-tet2-and-dnmt3a-on-cytarabine-cytotoxicity-in-different-populations
#20
Y Wang, J K Lamba
WHAT IS KNOWN AND OBJECTIVE: Cytarabine (ara-C) is the mainstay of treatment for acute myeloid leukaemia. Resistance and toxicity are common reasons for its treatment failure. Genetic variants of susceptibility genes may be involved in resistance and toxicity to ara-C. This study is aimed to explore the association between influence of genetic variants of IDH1, IDH2, TET2 and DNMT3A on cytarabine cytotoxicity in European and/or African populations. METHODS: HapMap cell lines derived from European descent (CEU) and African descent (YRI) were exposed to ara-C at different concentrations (1, 5, 40 and 80 μmol/L)...
November 21, 2017: Journal of Clinical Pharmacy and Therapeutics
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