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https://www.readbyqxmd.com/read/28415014/determination-and-quantification-of-intracellular-fludarabine-triphosphate-cladribine-triphosphate-and-clofarabine-triphosphate-by-lc-ms-ms-in-human-cancer-cells
#1
Jean-Yves Puy, Lars Petter Jordheim, Emeline Cros-Perrial, Charles Dumontet, Suzanne Peyrottes, Isabelle Lefebvre-Tournier
Purine nucleoside analogues are widely used in the treatment of haematological malignancies, and their biological activity is dependent on the intracellular accumulation of their triphosphorylated metabolites. In this context, we developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to study the formation of 5'-triphosphorylated derivatives of cladribine, fludarabine, clofarabine and 2'-deoxyadenosine in human cancer cells. Br-ATP was used as internal standard. Separation was achieved on a hypercarb column...
March 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28396162/phase-i-study-of-clofarabine-and-2-gy-total-body-irradiation-as-a-non-myeloablative-preparative-regimen-for-hematopoietic-stem-cell-transplantation-hsct-in-pediatric-patients-with-hematologic-malignancies-a-therapeutic-advances-in-childhood-leukemia-tacl-consortium
#2
Sandeep Soni, Hisham Abdel-Azim, Meghann McManus, Eneida Nemecek, Richard Sposto, Ann Woolfrey, Haydar Frangoul
Clofarabine is a purine nucleoside analog with immunosuppressive and anti-leukemic activity and its inclusion in reduced intensity regimens could potentially improve outcomes. We performed a prospective Phase I study of clofarabine combined with 2 Gy total body irradiation (TBI) as a non-myeloablative (NMA) preparative regimen for allogeneic stem cell transplantation in pediatric patients, who were considered at high risk of mortality from standard myeloablative regimens. The main goal of the study was to delineate the maximum feasible dose (MFD) of clofarabine in combination with 2 Gy TBI...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28262461/clofarabine-based-consolidation-therapy-in-aml
#3
Vicki Brower
No abstract text is available yet for this article.
April 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28229039/clofarabine-desensitization-a-case-report-leukemia-research-reports
#4
Sarah M Hayes, Justin A Wasko, Erica Dahl Warlick
We describe a relapsed AML patient who had two prior severe reactions to clofarabine involving rigors, emesis, tachycardia, hypotension, and acute kidney injury. Given previous prolonged remission achieved with clofarabine and cytarabine therapy years prior, rechallenge was undertaken upon discovery of AML relapse. We designed a desensitization protocol performed with the first dose of clofarabine, leading to successful administration of the entire clofarabine/cytarabine treatment course. From this case we show promise for clofarabine rechallenge after prior hypersensitivity reactions in patients with few treatment options for relapsed AML...
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28221862/randomized-phase-ii-study-of-clofarabine-based-consolidation-for-younger-adults-with-acute-myeloid-leukemia-in-first-remission
#5
Xavier Thomas, Stéphane de Botton, Sylvie Chevret, Denis Caillot, Emmanuel Raffoux, Emilie Lemasle, Jean-Pierre Marolleau, Céline Berthon, Arnaud Pigneux, Norbert Vey, Oumedaly Reman, Marc Simon, Christian Recher, Jean-Yves Cahn, Olivier Hermine, Sylvie Castaigne, Karine Celli-Lebras, Norbert Ifrah, Claude Preudhomme, Christine Terré, Hervé Dombret
Purpose To evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML). Patients and Methods Patients age 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twenty-one patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles...
April 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28220857/samhd1-enhances-nucleoside-analogue-efficacy-against-hiv-1-in-myeloid-cells
#6
Paula Ordonez, Simone Kunzelmann, Harriet C T Groom, Melvyn W Yap, Simon Weising, Chris Meier, Kate N Bishop, Ian A Taylor, Jonathan P Stoye
SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcription. We now show that, in addition to this direct effect on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220349/clofarabine-based-chemotherapy-as-a-bridge-to-transplant-in-the-setting-of-refractory-or-relapsed-acute-myeloid-leukemia-after-at-least-one-previous-unsuccessful-salvage-treatment-containing-fludarabine-a-single-institution-experience
#7
Alfredo Molteni, Marta Riva, Emanuele Ravano, Laura Marbello, Valentina Mancini, Giovanni Grillo, Elisa Zucchetti, Rosa Greco, Roberto Cairoli
For refractory or relapsed acute myeloid leukemia patients, allogeneic hematopoietic stem cell transplantation is the only curative treatment option, but the disease must be in remission before this can be attempted. "Salvage" therapy regimens containing high-dose cytarabine plus fludarabine or cladribine with or without anthracyclines or plus mitoxantrone and etoposide fail in 30-50% of cases. We report the outcome of 14 patients treated with a clofarabine-based treatment administered after at least one failed fludarabine-based "salvage" attempt in a "real life" (outside a clinical trial) context...
February 20, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28185203/hla-haploidentical-hematopoietic-cell-transplantation-using-clofarabine-and-busulfan-for-refractory-pediatric-hematological-malignancy
#8
Masatoshi Takagi, Yasuyoshi Ishiwata, Yuki Aoki, Satoshi Miyamoto, Akihiro Hoshino, Kazuaki Matsumoto, Akira Nishimura, Mari Tanaka, Masakatsu Yanagimachi, Noriko Mitsuiki, Kohsuke Imai, Hirokazu Kanegane, Michiko Kajiwara, Kanako Takikawa, Tsukasa Mae, Osamu Tomita, Junya Fujimura, Masato Yasuhara, Daisuke Tomizawa, Shuki Mizutani, Tomohiro Morio
Haploidentical hematopoietic cell transplantation (HCT) conditioning with clofarabine and target area under the blood concentration-time curve (AUC)-based busulfan adjustment was performed in three patients with refractory pediatric leukemia. The target AUC for two patients who had already received multiple transplantations was 3600 and 4000 μmol min/L, and that for the patient with Down's syndrome was 3000 μmol min/L. Regimen-related toxicity was well tolerated in all cases. All three maintained cytological remission throughout the follow-up period (between 31 and 167 weeks)...
February 9, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28049642/therapeutic-value-of-clofarabine-in-younger-and-middle-aged-18-65-yrs-adults-with-newly-diagnosed-aml
#9
Bob Löwenberg, Thomas Pabst, Johan Maertens, Yvette van Norden, Bart J Biemond, Harry C Schouten, Olivier Spertini, Edo Vellenga, Carlos Graux, Violaine Havelange, Georgine E de Greef, Okke de Weerdt, Marie-Cecile J C Legdeur, Juergen Kuball, Marinus van Marwijk Kooy, Bjorn T Gjertsen, Mojca Jongen-Lavrencic, Arjan A van de Loosdrecht, Daniëlle van Lammeren-Venema, Beata Hodossy, Dimitri A Breems, Yves Chalandon, Jakob Passweg, Peter J M Valk, Markus G Manz, Gert J Ossenkoppele
Clofarabine has demonstrated antileukemic activity in acute myeloid leukemia (AML) but has yet to be critically evaluated in younger adults in the frontline with standard chemotherapy. We compared two induction regimens in newly diagnosed patients aged 18-65 with AML/high risk MDS, i.e., idarubicine-cytarabine (cycle I) and amsacrine-cytarabine (cycle II) without or with clofarabine (10 mg/m(2) on days 1-5 of each of both cycles). Consolidation involved chemotherapy with or without hematopoietic stem cell transplantation...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28012306/interaction-of-anticancer-drug-clofarabine-with-human-serum-albumin-and-human-%C3%AE-1-acid-glycoprotein-spectroscopic-and-molecular-docking-approach
#10
Mohammad Rehan Ajmal, Saima Nusrat, Parvez Alam, Nida Zaidi, Mohsin Vahid Khan, Masihuz Zaman, Yasser E Shahein, Mohamed H Mahmoud, Gamal Badr, Rizwan Hasan Khan
The binding interaction between clofarabine, an important anticancer drug and two important carrier proteins found abundantly in human plasma, Human Serum Albumin (HSA) and α-1 acid glycoprotein (AAG) was investigated by spectroscopic and molecular modeling methods. The results obtained from fluorescence quenching experiments demonstrated that the fluorescence intensity of HSA and AAG is quenched by clofarabine and the static mode of fluorescence quenching is operative. UV-vis spectroscopy deciphered the formation of ground state complex between anticancer drug and the two studied proteins...
December 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27816651/clofarabine-plus-busulfan-is-an-effective-conditioning-regimen-for-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-acute-lymphoblastic-leukemia-long-term-study-results
#11
Partow Kebriaei, Roland Bassett, Genevieve Lyons, Ben Valdez, Celina Ledesma, Gabriela Rondon, Betul Oran, Stefan Ciurea, Amin Alousi, Uday Popat, Krina Patel, Sairah Ahmed, Amanda Olson, Qaiser Bashir, Nina Shah, Roy Jones, David Marin, Katayoun Rezvani, Yago Nieto, Issa Khouri, Muzaffar Qazilbash, Chitra Hosing, Elizabeth Shpall, Richard E Champlin, Borje S Andersson
We investigated the long-term safety and disease control data obtained with i.v. busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). A total of 107 patients, median age 38 years (range, 19 to 64 years) received a matched sibling donor (n = 52) or matched unrelated donor (n = 55) transplant for ALL in first complete remission (n = 62), second complete remission (n = 28), or more advanced disease (n = 17)...
February 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27811125/human-biodistribution-and-radiation-dosimetry-of-18f-cfa-a-pet-probe-targeting-the-deoxyribonucleoside-salvage-pathway
#12
Martin Barrio, Claudio Spick, Caius G Radu, Michael Lassmann, Uta Eberlein, Martin S Allen-Auerbach, Christiaan Schiepers, Roger Slavik, Johannes Czernin, Ken Herrmann
BACKGROUND: (18)F-Clofarabine ((18)F-CFA), a nucleotide purine analogue, is a substrate for deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. (18)F-CFA could be used to measure dCK expression and thus serve as a predictive biomarker for tumor responses to dCK dependent prodrugs or small molecule dCK inhibitors, respectively. As a prerequisite for clinical translation, we determined human whole body and organ dosimetry of (18)F-CFA. METHODS: Five healthy volunteers were injected intravenously with 232...
November 3, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27789677/low-dose-clofarabine-in-combination-with-a-standard-remission-induction-in-patients-aged-18-60-years-with-previously-untreated-intermediate-and-bad-risk-acute-myeloid-leukemia-or-high-risk-myelodysplastic-syndrome-combined-phase-i-ii-results-of-the-eortc-gimema
#13
LETTER
Dominik Selleslag, Stefan Suciu, Giovanna Meloni, Petra Muus, Constantijn J M Halkes, Adriano Venditti, Safaa M Ramadan, Hans Pruijt, Liv Meert, Marco Vignetti, Jean-Pierre Marie, Sébastian Wittnebel, Theo de Witte, Sergio Amadori, Roelof Willemze, Frédéric Baron
No abstract text is available yet for this article.
February 2017: Haematologica
https://www.readbyqxmd.com/read/27748046/clofarabine-versus-fludarabine-based-reduced-intensity-conditioning-regimen-prior-to-allogeneic-transplantation-in-adults-with-aml-mds
#14
Patrice Chevallier, Myriam Labopin, Regis Peffault de La Tour, Bruno Lioure, Claude-Eric Bulabois, Anne Huynh, Didier Blaise, Pascal Turlure, Etienne Daguindau, Natacha Maillard, Ibrahim Yakoub-Agha, Gaelle Guillerm, Jeremy Delage, Nathalie Contentin, Jacques-Olivier Bay, Florence Beckerich, Jean-Henri Bourhis, Marie Detrait, Stéphane Vigouroux, Sylvie François, Faezeh Legrand, Thierry Guillaume, Mohamad Mohty
We have retrospectively compared survivals between acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients who received either a clofarabine/busulfan (CloB2A2) or a fludarabine/busulfan (FB2A2) RIC regimen for allogeneic stem cell transplantation. Between 2009 and 2014, 355 allotransplanted cases were identified from the SFGM-TC registry as having received either the FB2A2 (n = 316, 56% males, median age: 59.2 years, AML 78.5%, first complete remission [CR1] 72%, median follow-up: 20 months) or the CloB2A2 (n = 39, 62% males, median age: 60...
November 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27741352/phase-2-study-of-low-dose-clofarabine-plus-cytarabine-for-patients-with-higher-risk-myelodysplastic-syndrome-who-have-relapsed-or-are-refractory-to-hypomethylating-agents
#15
Elias Jabbour, Stefan Faderl, Koji Sasaki, Tapan Kadia, Naval Daver, Naveen Pemmaraju, Keyur Patel, Joseph D Khoury, Carlos Bueso-Ramos, Zachary Bohannan, Farhad Ravandi, Gautam Borthakur, Srdan Verstovsek, Darla Miller, Rita Maduike, Chitra Hosing, Hagop M Kantarjian, Guillermo Garcia-Manero
BACKGROUND: The outcome of patients with higher risk myelodysplastic syndromes (MDS) after hypomethylating agent (HMA) failure is poor. This study evaluated the safety and activity of a combination of low-dose clofarabine and cytarabine for these patients. METHODS: Seventy patients with higher risk MDS who had no response, progressed, or relapsed after at least 4 cycles of HMA therapy were treated. RESULTS: The median age was 72 years. Thirty-nine percent of the patients had high-risk disease according to the International Prognostic Scoring System, and 50% of the patients had poor-risk cytogenetics...
October 14, 2016: Cancer
https://www.readbyqxmd.com/read/27624670/a-comparison-of-clofarabine-with-ara-c-each-in-combination-with-daunorubicin-as-induction-treatment-in-older-patients-with-acute-myeloid-leukaemia
#16
A K Burnett, N H Russell, R K Hills, J Kell, O J Nielsen, M Dennis, P Cahalin, C Pocock, S Ali, S Burns, S Freeman, D Milligan, R E Clark
The study was designed to compare clofarabine plus daunorubicin vs daunorubicin/ara-C in older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Eight hundred and six untreated patients in the UK NCRI AML16 trial with AML/high-risk MDS (median age, 67 years; range 56-84) and normal serum creatinine were randomised to two courses of induction chemotherapy with either daunorubicin/ara-C (DA) or daunorubicin/clofarabine (DClo). Patients were also included in additional randomisations; ± one dose of gemtuzumab ozogamicin in course 1; 2v3 courses and ± azacitidine maintenance...
February 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27621503/clofarabine-and-cytarabine-regimen-for-acute-myeloid-leukemia
#17
EDITORIAL
Kristin V Ho, Dominic A Solimando, J Aubrey Waddell
The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast...
November 2015: Hospital Pharmacy
https://www.readbyqxmd.com/read/27561720/sequential-regimen-of-clofarabine-cytosine-arabinoside-and-reduced-intensity-conditioned-transplantation-for-primary-refractory-acute-myeloid-leukemia
#18
Mohamad Mohty, Florent Malard, Didier Blaise, Noel Milpied, Gérard Socié, Anne Huynh, Oumédaly Reman, Ibrahim Yakoub-Agha, Sabine Furst, Thierry Guillaume, Resa Tabrizi, Stéphane Vigouroux, Pierre Peterlin, Jean El-Cheikh, Philippe Moreau, Myriam Labopin, Patrice Chevallier
The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included...
January 2017: Haematologica
https://www.readbyqxmd.com/read/27438145/prexasertib-a-chk1-chk2-inhibitor-increases-the-effectiveness-of-conventional-therapy-in-b-t-cell-progenitor-acute-lymphoblastic-leukemia
#19
Andrea Ghelli Luserna Di Rorà, Ilaria Iacobucci, Enrica Imbrogno, Cristina Papayannidis, Enrico Derenzini, Anna Ferrari, Viviana Guadagnuolo, Valentina Robustelli, Sarah Parisi, Chiara Sartor, Maria Chiara Abbenante, Stefania Paolini, Giovanni Martinelli
During the last few years many Checkpoint kinase 1/2 (Chk1/Chk2) inhibitors have been developed for the treatment of different type of cancers. In this study we evaluated the efficacy of the Chk 1/2 inhibitor prexasertib mesylate monohydrate in B-/T- cell progenitor acute lymphoblastic leukemia (ALL) as single agent and in combination with other drugs. The prexasertib reduced the cell viability in a dose and time dependent manner in all the treated cell lines. The cytotoxic activity was confirmed by the increment of apoptotic cells (Annexin V/Propidium Iodide staining), by the increase of γH2A...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27427921/a-multicenter-trial-of-myeloablative-clofarabine-and-busulfan-conditioning-for-relapsed-or-primary-induction-failure-aml-not-in-remission-at-the-time-of-allogeneic-hematopoietic-stem-cell-transplantation
#20
J Magenau, P Westervelt, S Khaled, J McGuirk, P Hari, M Eapen, P S Becker, B Parkin, T Braun, B Logan, H Wang, M Jagasia, S D Rowley, D D H Kim, T Schechter, N Frey, B Scott, T Churay, S Lieland, S Forman, S Mineishi
Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission...
January 2017: Bone Marrow Transplantation
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