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Clofarabine

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https://www.readbyqxmd.com/read/29200169/sinus-histiocytosis-with-massive-lymphadenopathy-rosai-dorfman-disease-diagnostic-and-treatment-modalities-for-this-rare-entity-revisited
#1
Andrew W Averitt, Kenneth Heym, Lauren Akers, Fernando Castro-Silva, Anish Ray
Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy is a rare non-Langerhans' cell histiocytic disease resulting from the proliferation and accumulation of sinus histiocytes within lymph nodes. Extranodal involvement frequently occurs, which increases the morbidity and mortality of the disease. There is no clear consensus with regard to the most effective diagnostic and treatment modalities. This report will focus on the diagnostic imaging, treatment, and outcomes for 3 cases of Rosai-Dorfman disease...
December 1, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29197676/intravenous-busulfan-compared-to-total-body-irradiation-pre-transplant-conditioning-for-adults-with-acute-lymphoblastic-leukemia
#2
Partow Kebriaei, Claudio Anasetti, Mei-Jie Zhang, Hai-Lin Wang, Ibrahim Aldoss, Marcos de Lima, H Jean Khoury, Brenda M Sandmaier, Mary M Horowitz, Andrew Artz, Nelli Bejanyan, Stefan Ciurea, Hillard M Lazarus, Robert Peter Gale, Mark Litzow, Christopher Bredeson, Matthew D Seftel, Michael A Pulsipher, Jaap-Jan Boelens, Joseph Alvarnas, Richard Champlin, Stephen Forman, Vinod Pullarkat, Daniel Weisdorf, David I Marks
Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (BU) to decrease toxicity. This retrospective study analyzed TBI and BU on outcomes of ALL patients aged 18-60 years, in first or second complete remission (CR), undergoing HLA-compatible sibling, related or unrelated donor HCT, reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29174506/discovery-of-novel-purine-nucleoside-derivatives-as-phosphodiesterase-2-pde2-inhibitors-structure-based-virtual-screening-optimization-and-biological-evaluation
#3
Xiaoxia Qiu, Yiyou Huang, Deyan Wu, Fei Mao, Jin Zhu, Wenzhong Yan, Hai-Bin Luo, Jian Li
Phosphodiesterase 2 (PDE2) has received much attention for the potential treatment of the central nervous system (CNS) disorders and pulmonary hypertension. Herein, we identified that clofarabine (4), an FDA-approved drug, displayed potential PDE2 inhibitory activity (IC50 = 3.12 ± 0.67 μM) by structure-based virtual screening and bioassay. Considering the potential therapeutic benefit of PDE2, a series of purine nucleoside derivatives based on the structure and binding mode of 4 were designed, synthesized and evaluated, which led to the discovery of the best compound 14e with a significant improvement of inhibitory potency (IC50 = 0...
November 14, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29152060/inhibition-of-chk1-sensitizes-ewing-sarcoma-cells-to-the-ribonucleotide-reductase-inhibitor-gemcitabine
#4
Kelli L Goss, Stacia L Koppenhafer, Kathryn M Harmoney, William W Terry, David J Gordon
Ewing sarcoma is a bone and soft tissue sarcoma that occurs in children and young adults. The EWS-FLI1 gene fusion is the driver mutation in most Ewing sarcoma tumors and functions, in part, as an aberrant transcription factor. We recently identified that Ewing sarcoma cells are sensitive to inhibition of ribonucleotide reductase (RNR), which catalyzes the formation of deoxyribonucleotides from ribonucleotides. In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100976/a-comparison-of-clofarabine-based-gclac-and-cladribine-based-clag-salvage-chemotherapy-for-relapsed-refractory-aml
#5
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...
September 22, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29039989/combination-of-clofarabine-cyclophosphamide-and-etoposide-for-relapsed-or-refractory-childhood-and-adolescent-acute-myeloid-leukemia
#6
Yoav Messinger, Jessica Boklan, John Goldberg, Steven G DuBois, Javier Oesterheld, Oussama Abla, Alissa Martin, Joanna Weinstein, Nobuko Hijiya
Relapsed/refractory acute myeloid leukemia (AML) has an extremely poor prognosis. We describe 17 children and adolescents with relapsed/refractory AML who received clofarabine, cyclophosphamide, and etoposide. Seven patients (41%) responded: 4 with a complete response (CR); 1 with CR with incomplete platelet recovery; and 2 with a partial response. Additionally, 4 developed hypocellular marrow without evidence of leukemia; 5 patients had resistant disease; and 1 suffered early toxic death. After further therapy including transplantation, 4 patients (24%) are alive without evidence of disease at a median of 60 months...
May 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/28978841/treatment-of-relapsed-or-refractory-acute-lymphoblastic-leukemia
#7
Kiyotoshi Imai
Most patients with adult acute lymphoblastic leukemia (ALL) undergo relapse, despite the achievement of complete remission with chemotherapy. Among patients with relapsed or refractory ALL, remission rates are 18-44% with the use of standard salvage chemotherapy, but the duration of remission is short. A major goal in this population is to induce remission with a sufficient duration to prepare for stem cell transplantation. The poor outcomes and lack of durable responses seen with conventional chemotherapy have led to the development of several novel agents, including clofarabine and nelarabine...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28945366/a-molecular-recognition-approach-to-synthesize-nucleoside-analogue-based-multifunctional-nanoparticles-for-targeted-cancer-therapy
#8
Dali Wang, Bing Liu, Yuan Ma, Chenwei Wu, Quanbing Mou, Hongping Deng, Ruibin Wang, Deyue Yan, Chuan Zhang, Xinyuan Zhu
Tumor-targeted drug delivery with simultaneous cancer imaging is highly desirable for personalized medicine. Herein, we report a supramolecular approach to design a promising class of multifunctional nanoparticles based on molecular recognition of nucleobases, which combine excellent tumor-targeting capability via aptamer, controlled drug release, and efficient fluorescent imaging for cancer-specific therapy. First, an amphiphilic prodrug dioleoyl clofarabine was self-assembled into micellar nanoparticles with hydrophilic nucleoside analogue clofarabine on their surface...
October 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28874539/detection-of-immune-responses-after-immunotherapy-in-glioblastoma-using-pet-and-mri
#9
Joseph P Antonios, Horacio Soto, Richard G Everson, Diana L Moughon, Anthony C Wang, Joey Orpilla, Caius Radu, Benjamin M Ellingson, Jason T Lee, Timothy Cloughesy, Michael E Phelps, Johannes Czernin, Linda M Liau, Robert M Prins
Contrast-enhanced MRI is typically used to follow treatment response and progression in patients with glioblastoma (GBM). However, differentiating tumor progression from pseudoprogression remains a clinical dilemma largely unmitigated by current advances in imaging techniques. Noninvasive imaging techniques capable of distinguishing these two conditions could play an important role in the clinical management of patients with GBM and other brain malignancies. We hypothesized that PET probes for deoxycytidine kinase (dCK) could be used to differentiate immune inflammatory responses from other sources of contrast-enhancement on MRI...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28810255/ponatinib-induced-graft-versus-host-disease-graft-versus-leukemia-effect-in-a-patient-with-philadelphia-positive-acute-lymphoblastic-leukemia-without-the-t315i-mutation-relapsing-after-allogeneic-transplant
#10
Annamaria Petrungaro, Massimo Gentile, Carla Mazzone, Rosa Greco, Giuseppina Uccello, Anna Grazia Recchia, Laura De Stefano, Sabrina Bossio, Angela Palummo, Rosellina Morelli, Caterina Musolino, Fortunato Morabito, Ernesto Vigna
We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i...
August 16, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28718728/a-phase-i-ii-randomized-trial-of-clofarabine-or-fludarabine-added-to-idarubicin-and-cytarabine-for-adults-with-relapsed-or-refractory-acute-myeloid-leukemia
#11
Nicholas J Short, Hagop Kantarjian, Farhad Ravandi, Xuelin Huang, Lianchun Xiao, Guillermo Garcia-Manero, William Plunkett, Varsha Gandhi, Koji Sasaki, Naveen Pemmaraju, Naval G Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Zeev Estrov, Tapan M Kadia, William G Wierda, Courtney D DiNardo, Mark Brandt, Susan M O'Brien, Jorge E Cortes, Elias Jabbour
The purine nucleoside analogues clofarabine and fludarabine are active in acute myeloid leukemia (AML). We conducted a phase I/II randomized study of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) for relapsed or refractory AML. Clofarabine 15 mg/m(2) was identified as the recommended phase II dose. Eighty-one patients were assigned using adaptive randomization to CIA (n = 48) or FIA (n = 33). The complete response (CR)/CR without platelet recovery rate did not differ between CIA and FIA (38% versus 30%, respectively; p = ...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28716944/potent-competitive-inhibition-of-human-ribonucleotide-reductase-by-a-nonnucleoside-small-molecule
#12
Md Faiz Ahmad, Intekhab Alam, Sarah E Huff, John Pink, Sheryl A Flanagan, Donna Shewach, Tessianna A Misko, Nancy L Oleinick, William E Harte, Rajesh Viswanathan, Michael E Harris, Chris Godfrey Dealwis
Human ribonucleotide reductase (hRR) is crucial for DNA replication and maintenance of a balanced dNTP pool, and is an established cancer target. Nucleoside analogs such as gemcitabine diphosphate and clofarabine nucleotides target the large subunit (hRRM1) of hRR. These drugs have a poor therapeutic index due to toxicity caused by additional effects, including DNA chain termination. The discovery of nonnucleoside, reversible, small-molecule inhibitors with greater specificity against hRRM1 is a key step in the development of more effective treatments for cancer...
August 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28708931/a-randomized-phase-2-study-of-idarubicin-and-cytarabine-with-clofarabine-or-fludarabine-in-patients-with-newly-diagnosed-acute-myeloid-leukemia
#13
Elias Jabbour, Nicholas J Short, Farhad Ravandi, Xuelin Huang, Lianchun Xiao, Guillermo Garcia-Manero, William Plunkett, Varsha Gandhi, Koji Sasaki, Naveen Pemmaraju, Naval G Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Zeev Estrov, Tapan M Kadia, William G Wierda, Courtney D DiNardo, Mark Brandt, Susan M O'Brien, Jorge E Cortes, Hagop Kantarjian
BACKGROUND: Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS: Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients)...
July 14, 2017: Cancer
https://www.readbyqxmd.com/read/28687003/inhibition-of-chk1-sensitizes-ewing-sarcoma-cells-to-the-ribonucleotide-reductase-inhibitor-gemcitabine
#14
Kelli L Goss, Stacia L Koppenhafer, Kathryn M Harmoney, William W Terry, David J Gordon
Ewing sarcoma is a bone and soft tissue sarcoma that occurs in children and young adults. The EWS-FLI1 gene fusion is the driver mutation in most Ewing sarcoma tumors and functions, in part, as an aberrant transcription factor. We recently identified that Ewing sarcoma cells are sensitive to inhibition of ribonucleotide reductase (RNR), which catalyzes the formation of deoxyribonucleotides from ribonucleotides. In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624910/clinical-pharmacology-and-clinical-trials-of-ribonucleotide-reductase-inhibitors-is-it-a-viable-cancer-therapy
#15
REVIEW
Mukundan Baskar Mannargudi, Subrata Deb
PURPOSE: Ribonucleotide reductase (RR) enzymes (RR1 and RR2) play an important role in the reduction of ribonucleotides to deoxyribonucleotides which is involved in DNA replication and repair. Augmented RR activity has been ascribed to uncontrolled cell growth and tumorigenic transformation. METHODS: This review mainly focuses on several biological and chemical RR inhibitors (e.g., siRNA, GTI-2040, GTI-2501, triapine, gemcitabine, and clofarabine) that have been evaluated in clinical trials with promising anticancer activity from 1960's till 2016...
August 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28538504/clofarabine-dosing-in-a-patient-with-acute-myeloid-leukemia-on-intermittent-hemodialysis-case-report-and-review-of-the-literature
#16
Lydia L Benitez, Katherine Gharibian, David Frame, Rajen Mody, Erika Mora
Clofarabine containing chemotherapeutic regimens have demonstrated efficacy in the treatment of relapsed refractory acute myeloid leukemia. Nonetheless, there are limited data on the use of clofarabine in patients with renal failure. The present report describes the use of clofarabine in a patient with renal failure undergoing intermittent dialysis. We describe our rationale for dosing, clofarabine plasma levels obtained, and discuss our findings in the context of other available literature. Consistent with previous findings, intermittent hemodialysis was not found to be a reliable method of removing clofarabine in patients with renal insufficiency...
August 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28527985/long-term-follow-up-and-impact-of-comorbidity-before-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-lessons-learned-from-the-prospective-bridge-trial
#17
Jan Moritz Middeke, Regina Herbst, Stefani Parmentier, Gesine Bug, Mathias Hänel, Gernot Stuhler, Kerstin Schäfer-Eckart, Wolf Rösler, Stefan Klein, Wolfgang Bethge, Ulrich Bitz, Bozena Büttner, Holger Knoth, Nael Alakel, Markus Schaich, Anke Morgner, Michael Kramer, Katja Sockel, Malte von Bonin, Friedrich Stölzel, Uwe Platzbecker, Christoph Röllig, Christian Thiede, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig
In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only treatment providing long-term disease control. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy before HSCT in patients with r/r AML. Here, we report the long-term follow-up of this phase II multicenter trial and exploratory analyses on the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range, 40 to 75) were enrolled...
September 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28509593/impact-of-pharmacokinetics-on-the-toxicity-and-efficacy-of-clofarabine-in-patients-with-relapsed-or-refractory-acute-myeloid-leukemia
#18
Bozena Büttner, Holger Knoth, Michael Kramer, Reinhard Oertel, Andreas Seeling, Katja Sockel, Malte von Bonin, Friedrich Stölzel, Nael Alakel, Uwe Platzbecker, Christoph Röllig, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Jan Moritz Middeke
Common side effects of clofarabine (CFB) are liver toxicity, particularly a transient elevation of transaminases and skin toxicity. We studied the correlation of pharmacokinetic (PK) parameters with these toxicities and the efficacy of CFB in patients with relapsed or refractory acute myeloid leukemia. Clofarabine PK parameters showed large inter-individual variability. A higher CFB area under the curve was significantly associated with higher transaminase levels (p = .011 for aspartate aminotransferase (AST), adjusted for age, sex, cumulated CFB dosage, baseline AST, and glomerular filtration rate (GFR))...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28462085/cellular-immune-profiling-after-sequential-clofarabine-and-lenalidomide-for-high-risk-myelodysplastic-syndromes-and-acute-myeloid-leukemia
#19
Prachi Jain, Jeffrey Klotz, Neil Dunavin, Kit Lu, Eleftheria Koklanaris, Debbie Draper, Jeanine Superata, Fariba Chinian, Quan Yu, Keyvan Keyvanfar, Susan Wong, Pawel Muranski, A John Barrett, Sawa Ito, Minoo Battiwalla
Patients with high risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) are commonly older with multiple co-morbidities, rendering them unsuitable for intensive induction chemotherapy or transplantation. We report preliminary cellular immune profiling of four cases receiving sequential clofarabine and lenalidomide for high risk MDS and AML in a phase I study. Our results highlight the potential of immune profiling for monitoring immune-modifying agents in high risk MDS and AML.
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28446463/the-national-cancer-institute-almanac-a-comprehensive-screening-resource-for-the-detection-of-anticancer-drug-pairs-with-enhanced-therapeutic-activity
#20
Susan L Holbeck, Richard Camalier, James A Crowell, Jeevan Prasaad Govindharajulu, Melinda Hollingshead, Lawrence W Anderson, Eric Polley, Larry Rubinstein, Apurva Srivastava, Deborah Wilsker, Jerry M Collins, James H Doroshow
To date, over 100 small-molecule oncology drugs have been approved by the FDA. Because of the inherent heterogeneity of tumors, these small molecules are often administered in combination to prevent emergence of resistant cell subpopulations. Therefore, new combination strategies to overcome drug resistance in patients with advanced cancer are needed. In this study, we performed a systematic evaluation of the therapeutic activity of over 5,000 pairs of FDA-approved cancer drugs against a panel of 60 well-characterized human tumor cell lines (NCI-60) to uncover combinations with greater than additive growth-inhibitory activity...
July 1, 2017: Cancer Research
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