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Clofarabine

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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
#1
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
#2
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
#3
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...
February 8, 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
#4
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...
February 23, 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
#5
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
#6
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...
February 7, 2018: Oncologist
https://www.readbyqxmd.com/read/29427526/nup98-bptf-gene-fusion-identified-in-primary-refractory-acute-megakaryoblastic-leukemia-of-infancy
#7
Mathieu Roussy, Mélanie Bilodeau, Loubna Jouan, Pauline Tibout, Louise Laramée, Emmanuelle Lemyre, Sophie Cardin, Camille Sauvageau, Françoise Couture, 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...
February 10, 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
#8
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
#9
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...
January 31, 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
#10
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
#11
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-with-total-body-irradiation-pretransplant-conditioning-for-adults-with-acute-lymphoblastic-leukemia
#12
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...
December 25, 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
#13
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
#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...
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
#15
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...
January 2018: 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
#16
MULTICENTER STUDY
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
#17
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
#18
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
#19
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
#20
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
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