The Experts below are selected from a list of 18 Experts worldwide ranked by ideXlab platform
Varsha Gandhi - One of the best experts on this subject based on the ideXlab platform.
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effect of fludarabine Cytarabine filgrastim and gemtuzumab ozogamicin flag go on relapse free survival in patients with newly diagnosed core binding factor acute myelogenous leukemia
Journal of Clinical Oncology, 2012Co-Authors: Gautam Borthakur, Varsha Gandhi, Farhad Ravandi, Jorge E. Cortes, Susan Obrien, Stefan Faderl, Tapan M Kadia, Zeev Estrov, William Plunkett, Joyce BassAbstract:6528 Background: Prior modulation with fludarabine increases Cytarabine-Triphosphate (ara-CTP) accumulation and granulocyte-colony-stimulating factor (G-CSF) increases the fludarabine-Triphosphate (F-ara-ATP) levels in leukemic blasts. Our front-line regimen of fludarabine, Cytarabine and filgrastim (FLAG) based on this rationale showed improved event-free survival compared to anthracycline and Cytarabine based regimens in patients (pts) with core-binding factor acute myelogenous leukemia (CBF-AML). Medical Research Council AML 15 trial reported survival benefit from addition of gemtuzumab ozogamicin (GO) to chemotherapy regimens in patients with favorable-risk cytogenetics AML. Methods: In a clinical trial combining GO (3 mg/m2 IV) with FLAG (FLAG-GO) in newly diagnosed CBF-AML, pts received GO on day 1 of induction and of post-remission cycles 2 or 3 and 5 or 6 in addition to FLAG. FLAG regimen was comprised of fludarabine 30 mg/m2 and Cytarabine 2 gm/m2 IV daily (both for 5 days in induction and 3-4 da...
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combination of cladribine and Cytarabine is effective for childhood acute myeloid leukemia results of the st jude aml97 trial
Leukemia, 2009Co-Authors: Jeffrey E Rubnitz, Varsha Gandhi, Kristine R Crews, Stanley Pounds, Shengping Yang, Dario Campana, Susana C Raimondi, James R Downing, Bassem I RazzoukAbstract:Because cladribine can increase Cytarabine Triphosphate levels, we tested a cladribine-Cytarabine combination in the St Jude AML97, trial in which this combination was administered before standard chemotherapy to 96 children with acute myeloid leukemia (AML) or myelodysplastic syndrome. Patients received a 5-day course of cladribine (9 mg/m(2) per dose) and Cytarabine either as daily 2-h infusions (500 mg/m(2) per dose) (arm A) or a continuous infusion (500 mg/m(2) per day) (arm B). Ara-CTP levels and inhibition of DNA synthesis increased from day 1 to day 2, but were not different between the two arms. In addition, the median blast percentages at day 15 did not differ between arms A and B, but patients treated in arm A had shorter intervals between the initiation of the first and second courses of therapy. Thus, although there were trends toward better complete remission rates and overall survival for patients treated in arm B, the reduced efficacy of arm A may have been partially compensated by more intense timing of therapy for that group. For all patients, 5-year event-free survival and overall survival estimates were 44.1+/-5.4 and 50.0+/-5.5%. Our results suggest that cladribine in combination with continuous-infusion Cytarabine is effective therapy for childhood AML.
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Biochemical modulation of Cytarabine Triphosphate by clofarabine.
Cancer chemotherapy and pharmacology, 2004Co-Authors: Todd Cooper, Mary Ayres, Billie Nowak, Varsha GandhiAbstract:Clofarabine has proven to be effective in the treatment of adult and pediatric acute myelogenous leukemia (AML). To investigate if clofarabine could be used with success in biochemical modulation strategies, we investigated the biochemical modulation of Cytarabine Triphosphate (ara-CTP) by clofarabine in a myeloid leukemia cell line and the effect of this combination on cytotoxicity. K562 cells were incubated with clofarabine and ara-C either sequentially or simultaneously to evaluate the combination effect on their phosphorylated metabolites. Clonogenic assays were used to determine the cytotoxicity of each agent alone and in combination. Deoxynucleotide analysis was performed to assess the effect of clofarabine on dNTPs. Clofarabine added either simultaneously or in sequence increased ara-CTP accumulation. The maximal modulation of ara-CTP accumulation occurred with 1 microM clofarabine. This level was achieved at the maximum tolerated dose for adult and pediatric patients with AML. With 10 microM ara-C alone, 86 microM ara-CTP had accumulated after 3 h. The optimal sequence for the drug combination, i.e., clofarabine followed 4 h later by ara-C, resulted in 248 microM ara-CTP at 3 h. Clofarabine accumulated maximally in the monophosphate form. Preincubation with ara-C did not affect the Triphosphate form, but it lowered clofarabine monophosphate. Clofarabine resulted in the intracellular decrease of dATP and dGTP levels. Clonogenic assays revealed that the combination of clofarabine and ara-C produced synergistic killing of myeloid leukemia cells. These findings demonstrate that combination of clofarabine followed by ara-C results in a biochemical modulation of ara-CTP and synergistic cell kill. These studies provide a compelling rationale for clinical trials using this combination regimen for adult and pediatric patients with AML.
Priyanka Mehta - One of the best experts on this subject based on the ideXlab platform.
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intracellular Cytarabine Triphosphate in circulating blasts post treatment predicts remission status in patients with acute myeloid leukemia
Experimental Hematology, 2019Co-Authors: Elizabeth Anderson, Barbara Rees, Jonathon Hull, Jonathan Heywood, Andrea Preston, Rachel Protheroe, Emily J Foulstone, Rosemary Greenwood, Vyv Salisbury, Priyanka MehtaAbstract:Cytarabine remains the backbone of therapy in acute myeloid leukemia (AML). The ability to assess intracellular Cytarabine Triphosphate (ara-CTP) levels in patients receiving Cytarabine represents a major goal in the prediction of treatment response. This study, conducted within a clinical setting, aimed to assess ara-CTP levels in circulating peripheral blasts from non-M3 AML patients receiving Cytarabine at one of three dosing levels, using a novel biosensor assay. Results from the initial 72 hours post-commencement were correlated with day 28 remission status, with feasibility parameters concurrently assessed. Intracellular ara-CTP was detectable in ex vivo blasts post-treatment for standard-dose (SD) and high-dose (HD) patients (p
Todd Cooper - One of the best experts on this subject based on the ideXlab platform.
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Biochemical modulation of Cytarabine Triphosphate by clofarabine.
Cancer chemotherapy and pharmacology, 2004Co-Authors: Todd Cooper, Mary Ayres, Billie Nowak, Varsha GandhiAbstract:Clofarabine has proven to be effective in the treatment of adult and pediatric acute myelogenous leukemia (AML). To investigate if clofarabine could be used with success in biochemical modulation strategies, we investigated the biochemical modulation of Cytarabine Triphosphate (ara-CTP) by clofarabine in a myeloid leukemia cell line and the effect of this combination on cytotoxicity. K562 cells were incubated with clofarabine and ara-C either sequentially or simultaneously to evaluate the combination effect on their phosphorylated metabolites. Clonogenic assays were used to determine the cytotoxicity of each agent alone and in combination. Deoxynucleotide analysis was performed to assess the effect of clofarabine on dNTPs. Clofarabine added either simultaneously or in sequence increased ara-CTP accumulation. The maximal modulation of ara-CTP accumulation occurred with 1 microM clofarabine. This level was achieved at the maximum tolerated dose for adult and pediatric patients with AML. With 10 microM ara-C alone, 86 microM ara-CTP had accumulated after 3 h. The optimal sequence for the drug combination, i.e., clofarabine followed 4 h later by ara-C, resulted in 248 microM ara-CTP at 3 h. Clofarabine accumulated maximally in the monophosphate form. Preincubation with ara-C did not affect the Triphosphate form, but it lowered clofarabine monophosphate. Clofarabine resulted in the intracellular decrease of dATP and dGTP levels. Clonogenic assays revealed that the combination of clofarabine and ara-C produced synergistic killing of myeloid leukemia cells. These findings demonstrate that combination of clofarabine followed by ara-C results in a biochemical modulation of ara-CTP and synergistic cell kill. These studies provide a compelling rationale for clinical trials using this combination regimen for adult and pediatric patients with AML.
Elizabeth Anderson - One of the best experts on this subject based on the ideXlab platform.
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intracellular Cytarabine Triphosphate in circulating blasts post treatment predicts remission status in patients with acute myeloid leukemia
Experimental Hematology, 2019Co-Authors: Elizabeth Anderson, Barbara Rees, Jonathon Hull, Jonathan Heywood, Andrea Preston, Rachel Protheroe, Emily J Foulstone, Rosemary Greenwood, Vyv Salisbury, Priyanka MehtaAbstract:Cytarabine remains the backbone of therapy in acute myeloid leukemia (AML). The ability to assess intracellular Cytarabine Triphosphate (ara-CTP) levels in patients receiving Cytarabine represents a major goal in the prediction of treatment response. This study, conducted within a clinical setting, aimed to assess ara-CTP levels in circulating peripheral blasts from non-M3 AML patients receiving Cytarabine at one of three dosing levels, using a novel biosensor assay. Results from the initial 72 hours post-commencement were correlated with day 28 remission status, with feasibility parameters concurrently assessed. Intracellular ara-CTP was detectable in ex vivo blasts post-treatment for standard-dose (SD) and high-dose (HD) patients (p
Mary Ayres - One of the best experts on this subject based on the ideXlab platform.
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Biochemical modulation of Cytarabine Triphosphate by clofarabine.
Cancer chemotherapy and pharmacology, 2004Co-Authors: Todd Cooper, Mary Ayres, Billie Nowak, Varsha GandhiAbstract:Clofarabine has proven to be effective in the treatment of adult and pediatric acute myelogenous leukemia (AML). To investigate if clofarabine could be used with success in biochemical modulation strategies, we investigated the biochemical modulation of Cytarabine Triphosphate (ara-CTP) by clofarabine in a myeloid leukemia cell line and the effect of this combination on cytotoxicity. K562 cells were incubated with clofarabine and ara-C either sequentially or simultaneously to evaluate the combination effect on their phosphorylated metabolites. Clonogenic assays were used to determine the cytotoxicity of each agent alone and in combination. Deoxynucleotide analysis was performed to assess the effect of clofarabine on dNTPs. Clofarabine added either simultaneously or in sequence increased ara-CTP accumulation. The maximal modulation of ara-CTP accumulation occurred with 1 microM clofarabine. This level was achieved at the maximum tolerated dose for adult and pediatric patients with AML. With 10 microM ara-C alone, 86 microM ara-CTP had accumulated after 3 h. The optimal sequence for the drug combination, i.e., clofarabine followed 4 h later by ara-C, resulted in 248 microM ara-CTP at 3 h. Clofarabine accumulated maximally in the monophosphate form. Preincubation with ara-C did not affect the Triphosphate form, but it lowered clofarabine monophosphate. Clofarabine resulted in the intracellular decrease of dATP and dGTP levels. Clonogenic assays revealed that the combination of clofarabine and ara-C produced synergistic killing of myeloid leukemia cells. These findings demonstrate that combination of clofarabine followed by ara-C results in a biochemical modulation of ara-CTP and synergistic cell kill. These studies provide a compelling rationale for clinical trials using this combination regimen for adult and pediatric patients with AML.
