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Clofarabine

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https://www.readbyqxmd.com/read/29899571/the-safety-and-efficacy-of-clofarabine-in-combination-with-high-dose-cytarabine-and-total-body-irradiation-myeloablative-conditioning-and-allogeneic-stem-cell-transplantation-in-children-adolescents-and-young-adults-caya-with-poor-risk-acute-leukemia
#1
Jessica Hochberg, Stacey Zahler, Mark B Geyer, Nan Chen, Jennifer Krajewski, Lauren Harrison, Olga Militano, M Fevzi Ozkaynak, Alexandra C Cheerva, Julie Talano, Theodore B Moore, Alfred P Gillio, Mark C Walters, Lee Ann Baxter-Lowe, Carl Hamby, Mitchell S Cairo
Acute leukemias in children with CR3, refractory relapse, or induction failure (IF) have a poor prognosis. Clofarabine has single agent activity in relapsed leukemia and synergy with cytarabine. We sought to determine the safety and overall survival in a Phase I/II trial of conditioning with clofarabine (doses 40 - 52 mg/m2 ), cytarabine 1000 mg/m2 , and 1200 cGy TBI followed by alloSCT in children, adolescents, and young adults with poor-risk leukemia. Thirty-seven patients; Age 12 years (1-22 years); ALL/AML: 34:3 (18 IF, 10 CR3, 13 refractory relapse); 15 related, 22 unrelated donors...
June 13, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29875430/a-comparison-of-flag-ida-and-daunorubicin-combined-with-clofarabine-in-high-risk-acute-myeloid-leukaemia-data-from-the-uk-ncri-aml17-trial
#2
A K Burnett, R K Hills, O J Nielsen, S Freeman, A Ali, P Cahalin, A Hunter, I F Thomas, N H Russell
No abstract text is available yet for this article.
June 6, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29872899/rare-childhood-hybrid-histiocytosis-of-the-central-nervous-system-diagnosed-by-stereotactic-brain-biopsy-with-marked-treatment-response-to-clofarabine
#3
J Foss-Skiftesvik, D Scheie, C Klausen, A Sehested, J Skjøth-Rasmussen
Histiocytosis is a heterogeneous group of disease entities, comprised by two main categories, namely Langerhans and non-Langerhans cell histiocytoses. Central nervous system involvement in histiocytosis is considered very rare and is often secondary to affection of anatomically related bone structures and/or multi-organ disease. We present a never-before described case of rare childhood histiocytosis with hybrid features of Langerhans cell histiocytosis and juvenile xanthogranuloma confined to the central nervous system in a 2- and a half-year-old boy with distinct treatment response to clofarabine...
June 5, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29773602/clofarabine-high-dose-cytarabine-and-liposomal-daunorubicin-in-pediatric-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-study
#4
Natasha K A van Eijkelenburg, Mareike Rasche, Essam Ghazaly, Michael N Dworzak, Thomas Klingebiel, Claudia Rossig, Guy Leverger, Jan Stary, Eveline S J M de Bont, Dana A Chitu, Yves Bertrand, Benoit Brethon, Brigitte Strahm, Inge M van der Sluis, Gertjan J L Kaspers, Dirk Reinhardt, C Michel Zwaan
Survival in children with relapsed/refractory acute myeloid leukemia is unsatisfactory. Treatment consists of one course fludarabine, cytarabine and liposomal daunorubicin, followed by fludarabine and cytarabine and stem-cell transplantation. Study ITCC 020/I-BFM 2009-02 aimed to identify the recommended phase 2 dose of clofarabine replacing fludarabine in the abovementioned combination regimen (3+3 design). Escalating dose-levels of clofarabine (20-40mg/m2/day x5days) and liposomal daunorubicin (40-0mg/m2/day) were administered with cytarabine (2g/m2/day x5days)...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29750747/haploidentical-donor-transplantation-using-a-novel-clofarabine-containing-conditioning-regimen-for-very-high-risk-hematologic-malignant-neoplasms
#5
Akshay Sharma, Guolian Kang, Anusha Sunkara, Hiroto Inaba, Sima Jeha, Shane J Cross, Terrence Geiger, Brandon Triplett
Recurrent/refractory hematologic malignancies have a poor prognosis, and there is a need for novel treatment regimens that can be tolerated by this heavily pretreated patient group. Clofarabine has antileukemic activity with an acceptable toxicity profile. In a phase I clinical trial (NCT00824135), we substituted clofarabine for fludarabine in a well-established reduced-intensity conditioning regimen for a T cell-depleted, mismatched-related (haploidentical) donor transplant backbone and explored the maximum tolerated dose of clofarabine in this combination in 15 patients undergoing hematopoietic cell transplantation for recurrent/refractory or secondary leukemia...
May 10, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29691269/implementation-of-a-pharmacy-managed-program-for-the-transition-of-chemotherapy-to-the-outpatient-setting
#6
Ali McBride, Christopher J Campen, James Camamo, Marie Maloney, Daniel Persky, Sandra E Kurtin, Nikki L Barket, Ravitharan Krishnadasan, Emad Elquza, Faiz Anwer, Kurt Weibel
PURPOSE: Implementation of a pharmacy-managed program for the transition of chemotherapy to the outpatient setting is described. SUMMARY: The University of Arizona Cancer Center and Banner-University Medical Center Tucson are affiliated not-for-profit academic medical centers in Tucson, Arizona, whose facilities include a hospital and ambulatory care clinics that maintain 3 outpatient infusion centers. The cancer center pharmacy currently employs 25 pharmacists, with 4 clinical pharmacists serving both the inpatient and outpatient treatment sites...
May 1, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29545911/impact-on-early-outcomes-and-immune-reconstitution-of-high-dose-post-transplant-cyclophosphamide-vs-anti-thymocyte-globulin-after-reduced-intensity-conditioning-peripheral-blood-stem-cell-allogeneic-transplantation
#7
Christelle Retière, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautreau-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Marie C Béné, Berthe-Marie Imbert, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier, Patrice Chevallier
We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) ( n = 30) or anti-thymocyte globulin ATG ( n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29542029/clofarabine-followed-by-haploidentical-stem-cell-transplant-using-fludarabine-busulfan-and-total-body-irradiation-with-post-transplant-cyclophosphamide-in-non-remission-aml
#8
Kevin Rakszawski, Kosuke Miki, David Claxton, Henry Wagner, Hiroko Shike, Shin Mineishi, Seema Naik
Approximately 30-40% of patients with acute myeloid leukemia (AML) experience induction failures. In these patients who do not achieve remission with two cycles of standard induction therapies, the probability of achieving remission with subsequent inductions is very limited. Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but high relapse rate and transplant-related mortality often preclude them to proceed to transplant. Thus, AML not in remission at time of HSCT remains a huge unmet need in current HSCT practice, particularly if the patient does not have an HLA-matched donor identified by the time of two induction failures...
March 14, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29475821/systematic-literature-review-of-treatment-options-and-clinical-outcomes-for-patients-with-higher-risk-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia
#9
REVIEW
Jill A Bell, Aaron Galaznik, Rachel Huelin, Michael Stokes, Yelan Guo, Robert J Fram, Douglas V Faller
High-dose chemotherapy with allogeneic hematopoietic stem cell transplantation (allo-HSCT) can produce long-term remission in patients with higher-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML). However, this treatment regimen is not appropriate for elderly and/or comorbid patients; in these cases, azacitidine is a standard treatment. This systematic review was conducted to evaluate real-world evidence of treatment options for patients with HR-MDS/CMML. Medline and Embase (January 2006 to May 2016) were searched, in addition to conference proceedings and treatment guideline reviews...
April 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29473342/clofarabine-exerts-antileukemic-activity-against-cytarabine-resistant-b-cell-precursor-acute-lymphoblastic-leukemia-with-low-deoxycytidine-kinase-expression
#10
Meixian Huang, Takeshi Inukai, Kunio Miyake, Yoichi Tanaka, Keiko Kagami, Masako Abe, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Eiji Sugihara, Atsushi Watanabe, Shinpei Somazu, Tamao Shinohara, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Kanji Sugita
Cytosine arabinoside (Ara-C) is one of the key drugs for the treatment of acute myeloid leukemia. It is also used for consolidation therapy of acute lymphoblastic leukemia (ALL). Ara-C is a deoxyadenosine analog and is phosphorylated to form cytosine arabinoside triphosphate (Ara-CTP) as an active form. In the first step of the metabolic pathway, Ara-C is phosphorylated to Ara-CMP by deoxycytidine kinase (DCK). However, the current cumulative evidence in the association of the Ara-C sensitivity in ALL appears inconclusive...
April 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29460780/3-3-%C3%A3-resolution-cryo-em-structure-of-human-ribonucleotide-reductase-with-substrate-and-allosteric-regulators-bound
#11
Edward J Brignole, Kuang-Lei Tsai, Johnathan Chittuluru, Haoran Li, Yimon Aye, Pawel A Penczek, JoAnne Stubbe, Catherine L Drennan, Francisco Asturias
Ribonucleotide reductases (RNRs) convert ribonucleotides into deoxyribonucleotides, a reaction essential for DNA replication and repair. Human RNR requires two subunits for activity, the α subunit contains the active site, and the β subunit houses the radical cofactor. Here, we present a 3.3-Å resolution structure by cryo-electron microscopy (EM) of a dATP-inhibited state of human RNR. This structure, which was determined in the presence of substrate CDP and allosteric regulators ATP and dATP, has three α2 units arranged in an α6 ring...
February 20, 2018: ELife
https://www.readbyqxmd.com/read/29438091/a-phase-i-dose-escalation-study-of-clofarabine-in-patients-with-relapsed-or-refractory-low-grade-or-intermediate-grade-b-cell-or-t-cell-lymphoma
#12
Francine Marie Foss, Terri Parker
LESSONS LEARNED: Clofarabine can be active in relapsed and refractory lymphoid malignancies on a weekly dosing schedule.Responses were seen in patients with T-cell lymphomas, including cutaneous T-cell lymphoma, but not in patients with aggressive B-cell lymphomas. BACKGROUND: Clofarabine is a second-generation purine nucleoside analog currently approved for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia. In adults, clofarabine has been investigated in several phase I and II trials as a single agent and in combination for relapsed or refractory acute leukemia...
April 2018: Oncologist
https://www.readbyqxmd.com/read/29427526/nup98-bptf-gene-fusion-identified-in-primary-refractory-acute-megakaryoblastic-leukemia-of-infancy
#13
Mathieu Roussy, Mélanie Bilodeau, Loubna Jouan, Pauline Tibout, Louise Laramée, Emmanuelle Lemyre, France Léveillé, Frédérique Tihy, Sophie Cardin, Camille Sauvageau, Françoise Couture, Isabelle Louis, Aurélien Choblet, Natalie Patey, Patrick Gendron, Michel Duval, Pierre Teira, Josée Hébert, Brian T Wilhelm, John K Choi, Tanja A Gruber, Henrique Bittencourt, Sonia Cellot
The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (∼10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60%-70% of cases and include RBM15-MKL1, CBFA2T3-GLIS2, NUP98-KDM5A and MLL rearrangements. In addition, another 4% of AMKL harbor NUP98 rearrangements (NUP98r), with yet undetermined fusion partners...
June 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29415603/a-real-world-study-of-clofarabine-and-cytarabine-combination-therapy-for-patients-with-acute-myeloid-leukemia
#14
Fiona He, Smarika Sapkota, Sarah Parker, Todd Defor, Erica Warlick, Celalettin Ustun, Craig Eckfeldt, Armin Rashidi, Andy Kurtzweil, Daniel Weisdorf, Nelli Bejanyan
Clofarabine and cytarabine (Clo + Ara-C) combinations have efficacy in treatment of acute myeloid leukemia (AML). We retrospectively analyzed clinical outcomes of 71 AML patients receiving Clo + Ara-C regimens at the University of Minnesota from 2011 to 2016: 44 patients (62%) had newly diagnosed AML and 27 patients (38%) had relapsed/refractory AML. The median age of patients was 69 years (interquartile range [IQR], 63-75 years). Nearly 60% of the patients had secondary AML, and about half of patients had adverse risk cytogenetics...
February 7, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29382926/clofarabine-inhibits-ewing-sarcoma-growth-through-a-novel-molecular-mechanism-involving-direct-binding-to-cd99
#15
Haydar Çelik, Marika Sciandra, Bess Flashner, Elif Gelmez, Neslihan Kayraklıoğlu, David V Allegakoen, Jeff R Petro, Erin J Conn, Sarah Hour, Jenny Han, Lalehan Oktay, Purushottam B Tiwari, Mutlu Hayran, Brent T Harris, Maria Cristina Manara, Jeffrey A Toretsky, Katia Scotlandi, Aykut Üren
Ewing sarcoma (ES) is an aggressive bone and soft tissue malignancy that predominantly affects children and adolescents. CD99 is a cell surface protein that is highly expressed on ES cells and is required to maintain their malignancy. We screened small molecule libraries for binding to extracellular domain of recombinant CD99 and subsequent inhibition of ES cell growth. We identified two structurally similar FDA-approved compounds, clofarabine and cladribine that selectively inhibited the growth of ES cells in a panel of 14 ES vs...
April 2018: Oncogene
https://www.readbyqxmd.com/read/29288428/outcomes-of-previously-untreated-elderly-patients-with-aml-a-propensity-score-matched-comparison-of-clofarabine-vs-flag
#16
COMPARATIVE STUDY
Gianni B Scappaticci, Bernard L Marini, Victoria R Nachar, James R Uebel, Vera Vulaj, Ashley Crouch, Dale L Bixby, Moshe Talpaz, Anthony J Perissinotti
The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction...
April 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29200169/sinus-histiocytosis-with-massive-lymphadenopathy-rosai-dorfman-disease-diagnostic-and-treatment-modalities-for-this-rare-entity-revisited
#17
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...
May 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29197676/intravenous-busulfan-compared-with-total-body-irradiation-pretransplant-conditioning-for-adults-with-acute-lymphoblastic-leukemia
#18
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 18-60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014...
April 2018: 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
#19
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...
January 1, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29152060/inhibition-of-chk1-sensitizes-ewing-sarcoma-cells-to-the-ribonucleotide-reductase-inhibitor-gemcitabine
#20
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
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