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refractory acute leukemia

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https://www.readbyqxmd.com/read/29453291/lsd1-inhibition-exerts-its-anti-leukemic-effect-by-recommissioning-pu-1-and-c-ebp%C3%AE-dependent-enhancers-in-aml
#1
Monica Cusan, Sheng F Cai, Helai P Mohammad, Andrei Krivtsov, Alan Chramiec, Evangelia Loizou, Matthew D Witkin, Kimberly N Smitheman, Daniel G Tenen, Min Ye, Britta Will, Ulrich Steidl, Ryan G Kruger, Ross L Levine, Hugh Y Rienhoff, Richard P Koche, Scott A Armstrong
Epigenetic regulators are recurrently mutated and aberrantly expressed in acute myeloid leukemia (AML). Targeted therapies designed to inhibit these chromatin-modifying enzymes, such as the histone demethylase lysine specific demethylase 1 (LSD1) and the histone methyltransferase DOT1L, have been developed as novel treatment modalities for these often refractory diseases. A common feature of many of these targeted agents is their ability to induce myeloid differentiation, suggesting that multiple paths toward a myeloid gene expression program can be engaged to relieve the differentiation blockade that is uniformly seen in AML...
February 16, 2018: Blood
https://www.readbyqxmd.com/read/29451276/tisagenlecleucel-an-approved-anti-cd19-chimeric-antigen-receptor-t-cell-therapy-for-the-treatment-of-leukemia
#2
Y Liu, X Chen, W Han, Y Zhang
On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). This was a milestone in tumor immunology on account of the significant antitumor effect of tisagenlecleucel for the treatment of relapsed/refractory B-ALL patients. Conventional standard therapies for B-ALL have high failure rates, thus developing new therapies is crucial for patients with B-ALL...
November 2017: Drugs of Today
https://www.readbyqxmd.com/read/29449681/secondary-philadelphia-chromosome-acquired-during-therapy-of-acute-leukemia-and-myelodysplastic-syndrome
#3
Habibe Kurt, Lan Zheng, Hagop M Kantarjian, Guilin Tang, Farhad Ravandi-Kashani, Guillermo Garcia-Manero, Zimu Gong, Hesham M Amin, Sergej N Konoplev, Mark J Routbort, Xin Han, Wei Wang, L Jeffery Medeiros, Shimin Hu
The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is a defining event in chronic myeloid leukemia. It is also observed in several types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T lymphoblastic leukemia. Acquisition of the Philadelphia chromosome during therapy of acute leukemia and myelodysplastic syndrome is rare. We reported 19 patients, including 11 men and 8 women with a median age of 53 years at initial diagnosis...
February 14, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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
#4
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/29437791/a-phase-i-study-of-cpi-613-in-combination-with-high-dose-cytarabine-and-mitoxantrone-for-relapsed-or-refractory-acute-myeloid-leukemia
#5
Timothy S Pardee, Rebecca G Anderson, Kristin M Pladna, Scott Isom, Lais P Ghiraldeli, Lance D Miller, Jeff A Chou, Guangxu Jin, Wei Zhang, Leslie R Ellis, Dmitriy Berenzon, Dianna S Howard, David Hurd, Megan Manuel, Sarah Dralle, Susan Lyerly, Bayard L Powell
PURPOSE: CPI-613, a lipoate analog that inhibits pyruvate dehydrogenase (PDH) and α-ketogluterate dehydrogenase (KGDH) has activity in patients with myeloid malignancies. This study explored the role of mitochondrial metabolism in chemotherapy response, determined the maximally tolerated dose, efficacy and safety of CPI-613 combined with high dose cytarabine and mitoxantrone in patients with relapsed or refractory acute myeloid leukemia. METHODS: The role of mitochondrial response to chemotherapy was assessed in cell lines and animal models...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29434963/a-rare-e14a3-bcr-abl-fusion-transcript-in-acute-lymphoblastic-leukemia-patient-treated-with-car-modified-t-cell-therapy
#6
Haodong Cai, Li Yang, Kefeng Shen, Wei Zhang, Jie Xiong, Meilan Zhang, Xia Mao, Ying Wang, Min Xiao
E14a3 breakpoint cluster region (BCR)/ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL) fusion transcript is rare in Philadelphia chromosome positive disease, particularly in acute lymphoblastic leukemia (ALL). Recently an e14a3 fusion transcript was detected by multiple laboratory examinations, and the patient was suffering from ALL. Except for the BCR/ABL fusion gene, in the present study the patient additionally had an IKAROS family zinc finger 1 deletion which, has been confirmed as a significant adverse prognosis factor...
February 2018: Oncology Letters
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/29423036/salvaged-allogeneic-hematopoietic-stem-cell-transplantation-for-pediatric-chemotherapy-refractory-acute-leukemia
#8
Jingbo Wang, Lei Yuan, Haoyu Cheng, Xinhong Fei, Yumin Yin, Jiangying Gu, Song Xue, Junbao He, Fan Yang, Xiaocan Wang, Yixin Yang, Weijie Zhang
There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29417201/cd19-targeted-car-t-therapy-versus-chemotherapy-in-re-induction-treatment-of-refractory-relapsed-acute-lymphoblastic-leukemia-results-of-a-case-controlled-study
#9
Guoqing Wei, Yongxian Hu, Chengfei Pu, Jian Yu, Yi Luo, Jimin Shi, Qu Cui, Wenjun Wu, Jinping Wang, Lei Xiao, Zhao Wu, He Huang
Chimeric antigen receptor modified T cells against CD19 (CART19s) have potent anti-leukemia activities in patients with refractory/relapsed acute lymphoblastic leukemia (R/R ALL). This study was designed to investigate the correlation between safety/efficacy and therapeutic modalities including chemotherapy and CART19 therapy. Total 23 and 69 patients were enrolled in the CART19 group and in the chemotherapy group, respectively. The safety and efficacy profiles of 66 and 22 patients in the 2 groups were evaluated...
February 7, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29416633/allogeneic-hematopoietic-stem-cell-transplantation-for-relapsed-acute-myeloid-leukemia-in-eto-positive-with-reduced-intensity-conditioning
#10
Zhi Guo, Chen Xu, Hu Chen
Objective: This research is conducted under the intention of exploring the efficacy and safety of reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed ETO positive acute myeloid leukemia (AML). Materials and Methods: Treatment of 15 cases referring to recurrent ETO positive acute myeloid leukemia in an army hospital from January 2010 to January 2013 through allo-HSCT with reduced-intensity conditioning...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415603/a-real-world-study-of-clofarabine-and-cytarabine-combination-therapy-for-patients-with-acute-myeloid-leukemia
#11
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/29412158/allogeneic-hematopoietic-stem-cell-transplantation-for-gata2-deficiency-using-a-busulfan-based-regimen
#12
Mark Parta, Nirali N Shah, Kristin Baird, Hind Rafei, Katherine R Calvo, Thomas Hughes, Kristen Cole, Meg Kenyon, Bazetta Blacklock Schuver, Jennifer Cuellar-Rodriguez, Christa S Zerbe, Steven M Holland, Dennis D Hickstein
Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. The intensity of conditioning required to achieve reliable engraftment and prevent relapse remains unclear. Here, we describe the results of a prospective study of HSCT in 22 patients with GATA2 deficiency using a busulfan-based conditioning regimen. The study includes 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients...
February 2, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29411126/febrile-events-in-acute-lymphoblastic-leukemia-a-prospective-observational-multicentric-seifem-study-seifem-2012-b-all
#13
Roberta Di Blasi, Chiara Cattaneo, Russell E Lewis, Mario Tumbarello, Laura Angelici, Giulia Dragonetti, Alessandro Busca, Benedetta Cambò, Anna Candoni, Monica Cesarini, Simone Cesaro, Mario Delia, Rosa Fanci, Francesca Farina, Mariagrazia Garzia, Antonio Giordano, Bruno Martino, Lorella Melillo, Gianpaolo Nadali, Vincenzo Perriello, Marco Picardi, Angela Maria Quinto, Prassede Salutari, Angelica Spolzino, Adriana Vacca, Calogero Vetro, Michelle Zancanella, Annamaria Nosari, Franco Aversa, Livio Pagano
The purpose of the present study is to estimate the current incidence of febrile events (FEs) and infectious episodes in acute lymphoblastic leukemia (ALL) and evaluate the outcome. We analyzed data on all FEs in a cohort of patients affected by ALL admitted to 20 Italian hematologic centers during 21 months of observation from April 1, 2012 to December 31, 2013. Data about treatment phase, steroids, neutropenia, type and site of infection, and outcome of infection were collected. The population comprehended 271 ALL adult patients...
February 7, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29409351/cd33-specific-chimeric-antigen-receptor-t-cells-with-different-costimulators-showed-potent-anti-leukemia-efficacy-and-different-phenotype
#14
Saisai Li, Zhongfei Tao, Yingxi Xu, Jia Liu, Na An, Ying Wang, Haiyan Xing, Zheng Tian, Kejing Tang, Xiaolong Liao, Qing Rao, Min Wang, Jianxiang Wang
Acute myeloid leukemia (AML) is a kind of a malignant hematologic tumor caused by uncontrolled repopulation of myeloid hematopoietic stem cells (HSCs). Current therapeutic effects for AML patients are unsatisfactory. Especially relapsed and refractory AML still have poor prognosis. T cell modified by chimeric antigen receptor (CAR) is an immunotherapeutic strategy for malignancies, which has a broad developing prospect. Most of AML cells overexpress the myeloid antigen CD33. Therefore, CD33-specific CAR-T cells with different costimulators (CD28, 4-1BB or both, referred to as CD33 28z...
February 6, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29407586/8q24-myc-rearrangement-is-a-recurrent-cytogenetic-abnormality-in-blastic-plasmacytoid-dendritic-cell-neoplasms
#15
Prajwal C Boddu, Sa A Wang, Naveen Pemmaraju, Zhenya Tang, Shimin Hu, Shaoying Li, Jie Xu, L Jeffrey Medeiros, Guilin Tang
8q24/MYC rearrangements resulting in MYC overexpression occur most frequently in lymphoid neoplasms. MYC rearrangements rarely have been described in blastic plasmacytoid dendritic cell neoplasm (BPDCN). Over an 8-year period in our hospital, 5 of 41 (12%) patients with BPDCN were shown 8q24/MYC rearrangements, including 2 with t(6;8)(p21;q24), 1 with t(8;14)(q24;q32), 1 with t(X;8)(q24;q24), and 1 with t(3;8)(p25;q24). 8q24/MYC rearrangement was present in the stemline in 4 patients and in the sideline in one; the latter was a patient with primary myelofibrosis who then developed BPDCN...
February 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29407318/treatment-of-high-risk-acute-myeloid-leukemia-with-cladribine-cytarabine-mitoxantrone-and-granulocyte-colony-stimulating-factor-then-subsequent-bridging-to-myeloablative-allogeneic-hematopoietic-stem-cell-transplantation-a-case-series
#16
J Zhang, Y Sun, X Zhang, B Long, Y Lu, X Li
This report preliminarily evaluates the efficacy and safety of cladribine, cytarabine, mitoxantrone, and granulocyte colony-stimulating factor (CLAG-M) as bridging therapy to myeloablative allogeneic hematopoietic cell transplantation (allo-HCT) in the treatment of patients with refractory or relapsed acute myeloid leukemia. Five patients with high-risk refractory or relapsed acute myeloid leukemia received the CLAG-M regimen and subsequent bridging to myeloablative allo-HCT between December 2014 and August 2015 in our hospital...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29407182/report-of-the-relapsed-refractory-cohort-of-swog-s0919-a-phase-2-study-of-idarubicin-and-cytarabine-in-combination-with-pravastatin-for-acute-myelogenous-leukemia-aml
#17
Anjali S Advani, Hongli Li, Laura C Michaelis, Bruno C Medeiros, Michaela Liedtke, Alan F List, Kristen O'Dwyer, Megan Othus, Harry P Erba, Frederick R Appelbaum
Inhibition of cholesterol synthesis and uptake sensitizes acute myeloid leukemia (AML) blasts to chemotherapy. A Phase 2 study of high dose pravastatin given in combination with idarubicin and cytarabine demonstrated an impressive response rate [75% complete remission (CR), CR with incomplete count recovery (CRi)]. However, this population was a favorable risk group as eligible patients had to have a CR/CRi lasting ≥3 months following their most recent chemotherapy. Therefore, the study was amended to treat patients with poor risk disease including those with CR/CRi <6 months following their last induction regimen or with refractory disease...
January 31, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29401102/acquired-hypofibrinogenemia-before-asparaginase-exposure-during-induction-therapy-for-pediatric-acute-lymphoblastic-leukemia-a-report-of-2-cases-and-review-of-the-literature
#18
Sunil S Raikar, James Felker, Kavita N Patel, Glen Lew, Robert F Sidonio
Coagulopathy in pediatric leukemia patients is typically associated with acute promyelocytic leukemia or after asparaginase use in acute lymphoblastic leukemia. Rarely seen in acute lymphoblastic leukemia, we report 2 patients who presented with normal coagulation markers, but subsequently developed severe hypofibrinogenemia and bleeding in induction before administration of asparaginase. In both cases, cryoprecipitate was administered as initial treatment for bleeding associated with the hypofibrinogenemia...
February 2, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29392425/a-phase-i-ii-study-of-plerixafor-in-combination-with-fludarabine-idarubicin-cytarabine-and-g-csf-pleriflag-regimen-for-the-treatment-of-patients-with-the-first-early-relapsed-or-refractory-acute-myeloid-leukemia
#19
David Martínez-Cuadrón, Blanca Boluda, Pilar Martínez, Juan Bergua, Rebeca Rodríguez-Veiga, Jordi Esteve, Susana Vives, Josefina Serrano, Belen Vidriales, Olga Salamero, Lourdes Cordón, Amparo Sempere, Ana Jiménez-Ubieto, Julio Prieto-Delgado, Marina Díaz-Beyá, Ana Garrido, Celina Benavente, José Antonio Pérez-Simón, Federico Moscardó, Miguel A Sanz, Pau Montesinos Fernández
Clinical outcomes of patients with acute myeloid leukemia (AML) showing the first primary refractory or early-relapsed disease remain very poor. The Programa Español de Tratamientos en Hematología (PETHEMA) group designed a phase I-II trial using FLAG-Ida (fludarabine, idarubicin, cytarabine, and G-CSF) plus high-dose intravenous plerixafor, a molecule inducing mobilization of blasts through the SDF-1α-CXCR4 axis blockade and potentially leading to chemosensitization of the leukemic cells. We aimed to establish a recommended phase 2 dose (RP2D) of plerixafor plus FLAG-Ida, as well as the efficacy and safety of this combination for early-relapsed (first complete remission (CR/CRi) < 12 months) or primary refractory AML...
February 2, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29390924/a-4-gene-expression-prognostic-signature-might-guide-post-remission-therapy-in-patients-with-intermediate-risk-cytogenetic-acute-myeloid-leukemia
#20
Montserrat Torrebadell, Marina Díaz-Beyá, Susana G Kalko, Marta Pratcorona, Josep Nomdedeu, Alfons Navarro, Bernat Gel, Salut Brunet, Jorge Sierra, Mireia Camós, Jordi Esteve
In intermediate-risk cytogenetic acute myeloid leukemia (IRC-AML) patients, novel biomarkers to guide post-remission therapy are needed. We analyzed with high-density arrays 40 IRC-AML patients who received a non-allogeneic hematopoietic stem-cell transplantation-based post-remission therapy, and identified a signature that correlated with early relapse. Subsequently, we analyzed selected 187 genes in 49 additional IRC-AML patients by RT-PCR. BAALC, MN1, SPARC and HOPX overexpression correlated to refractoriness...
February 2, 2018: Leukemia & Lymphoma
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