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refractory acute leukemia

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https://www.readbyqxmd.com/read/28541716/investigational-bet-bromodomain-protein-inhibitors-in-early-stage-clinical-trials-for-acute-myelogenous-leukemia-aml
#1
Thorsten Braun, Claude Gardin
Acute myelogenous leukemia (AML) is a heterogeneous group of malignancies driven by genetic mutations and deregulated epigenetic control. Relapse/refractory disease remains frequent in younger patients and even more so in older patients, including treatment with epigenetic drugs in this age group, mainly with hypomethylating agents. New treatment strategies are urgently needed. The recent discovery that epigenetic readers of the bromodomain (BRD) and extraterminal (BET) protein family, are crucial for AML maintenance by transcription of oncogenic c-MYC lead to rapid development of BET inhibitors entering clinical trials...
May 25, 2017: Expert Opinion on Investigational Drugs
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
#2
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...
May 22, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28533941/changes-in-clinical-laboratory-parameters-and-pharmacodynamic-markers-in-response-to-blinatumomab-treatment-of-patients-with-relapsed-refractory-all
#3
Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S Topp, Nicola Gökbuget, Patrick A Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger
BACKGROUND: Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS: Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28532177/targeting-non-hodgkin-lymphoma-with-blinatumomab
#4
Sheilagh Sanders, Douglas A Stewart
Management of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) remains challenging, and novel effective agents are eagerly awaited. Blinatumomab is a bispecific T-cell engager, targeting CD19. While blinatumomab's primary clinical use has been in B-cell acute lymphoblastic leukemia (B-ALL), there are increasing data for its use in B-lineage lymphomas. Areas covered: The aim of this review is to highlight the clinical data for blinatumomab use in NHL. Herein, the authors provide an overview of blinatumomab, its mechanism of action, its proven efficacy against B-ALL, and its phase I-II data assessing its use in NHL Expert opinion: Blinatumomab has modest activity in phase I-II trials in NHL, and may represent a means of bridging patients with relapsed disease to hematopoietic stem cell transplant...
May 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28525644/risk-factors-and-clinical-outcomes-of-breakthrough-yeast-bloodstream-infections-in-patients-with-hematological-malignancies-in-the-era-of-newer-antifungal-agents
#5
Si-Hyun Kim, Jae-Ki Choi, Sung-Yeon Cho, Hyo-Jin Lee, Sun Hee Park, Su-Mi Choi, Dong-Gun Lee, Jung-Hyun Choi, Jin-Hong Yoo, Jong-Wook Lee
Although yeast bloodstream infections (BSIs) are increasingly being reported in patients with hematological malignancies undergoing antifungal therapy, clinical information regarding breakthrough infections is scarce. The aim of this study was to determine the risk factors for and clinical outcomes of breakthrough yeast BSIs in patients with hematological malignancies in the era of newer antifungal agents. Between 2011 and 2014, all consecutive patients with hematological malignancies who developed yeast BSIs were included in a case-control study wherein breakthrough infections (cases) and de novo infections (controls) were compared...
May 19, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28521413/chromosome-t-7-11-p15-p15-translocation-in-acute-myeloid-leukemia-coexisting-with-multilineage-dyspoiesis-and-mutations-in-nras-and-wt1-a-case-report-and-literature-review
#6
Jingke Yang, Xiaodong Lyu, Xinghu Zhu, Xiangguang Meng, Wenli Zuo, Hao Ai, Mei Deng
The chromosomal translocation t(7;11)(p15;p15) and the resulting nucleoporin 98-homeobox A9 (NUP98-HOXA9) gene fusion is rare but recurrent genetic abnormity in acute myeloid leukemia (AML). The present study describes a case of AML plus maturation (-M2) with multilineage dyspoiesis in a 30-year-old male in whom a 46,XY,t(7;11)(p15;p15) karyotype was detected through chromosome analysis. Subsequent molecular and sequencing analysis demonstrated a NUP98-HOXA9 fusion gene with a type I fusion between NUP98 exon 12 and HOXA9 exon 1b, and mutations in neuroblastoma V-Ras oncogene homolog and Wilms tumor 1...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28518151/disulfiram-copper-selectively-eradicates-aml-leukemia-stem-cells-in-vitro-and-in-vivo-by-simultaneous-induction-of-ros-jnk-and-inhibition-of-nf-%C3%AE%C2%BAb-and-nrf2
#7
Bing Xu, Shiyun Wang, Rongwei Li, Kai Chen, Lingli He, Manman Deng, Vinodh Kannappan, Jie Zha, Huijuan Dong, Weiguang Wang
Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs...
May 18, 2017: Cell Death & Disease
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
#8
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/28509405/opportunities-for-expanding-clinical-trial-enrollment-for-relapsed-and-refractory-pediatric-acute-myeloid-leukemia-in-the-united-states-and-canada
#9
Thomas B Alexander, Nickhill Bhakta, E Anders Kolb, Jeffrey E Rubnitz
No abstract text is available yet for this article.
May 16, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28508228/relationship-between-white-blood-cell-count-elevation-and-clinical-response-after-g-csf-priming-chemotherapy-for-acute-myeloid-leukemia
#10
Daisuke Minakata, Shin-Ichiro Fujiwara, Takashi Ikeda, Yumiko Toda, Shoko Ito, Kiyomi Mashima, Kento Umino, Hirofumi Nakano, Ryoko Yamasaki, Kaoru Morita, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
We retrospectively analyzed the relationship between white blood cell (WBC) count elevation after priming and clinical response in 115 patients with AML (61 untreated and 54 relapsed or refractory) treated with low-dose cytarabine, aclarubicin, and G-CSF priming. Receiver operating characteristic curve analysis showed that the ratio of maximum WBC count to pretreatment WBC count (WBCratio) was most strongly associated with complete remission (CR) in previously untreated patients among several parameters we analyzed in this study; however, the prediction accuracy was not clinically significant considering the area under the curve of 0...
May 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28504666/conditioning-regimens-for-allogeneic-hematopoietic-stem-cell-transplants-in-acute-myeloid-leukemia
#11
REVIEW
Y S Jethava, S Sica, B Savani, F Socola, M Jagasia, M Mohty, A Nagler, A Bacigalupo
AML is currently the first indication for allogeneic hematopoietic stem cell transplantation (allo-HSCT), as shown by international transplant registries. The conditioning regimens are classified as myeloablative conditioning, non-myeloablative or reduced intensity conditioning. Targeted radioimmunotherapy such as anti-CD45 antibody have also been added to the conditioning regimen in an attempt to improve tumor cell kill. Refinement of standard regimens has led to a reduction of non-relapse mortality, also in the older age group over 60 or 70 years of age...
May 15, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28504025/the-preclinical-discovery-of-vosaroxin-for-the-treatment-of-acute-myeloid-leukemia
#12
Etienne Paubelle, Florence Zylbersztejn, Xavier Thomas
Acute myeloid leukemia (AML) represents a disease with a very poor outcome and remains an area of significant unmet need necessitating novel therapeutic strategies. Among novel therapeutic agents, vosaroxin is a first-in-class anticancer quinolone derivative that targets topoisomerase II and induces site-selective double-strand breaks in DNA, leading to tumor cell apoptosis. Area covered: Herein, the authors provide a comprehensive review of the preclinical development of vosaroxin. This includes coverage of vosaroxin's mechanism of action in addition to its pharmacology and of the main studies reported over the past few years with vosaroxin when used to treat adult AML...
May 13, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28499732/activity-of-resveratrol-triesters-against-primary-acute-lymphoblastic-leukemia-cells
#13
Alicja Urbaniak, Magdalena Delgado, Karol Kacprzak, Timothy C Chambers
Resveratrol is a common polyphenol of plant origin known for its cancer prevention and other properties. Its wider application is limited due to poor water solubility, low stability, and weak bioavailability. To overcome these limitations, a series of 13 novel resveratrol triesters were synthesized previously. In this paper, we describe the synthesis of 3 additional derivatives and the activity of all 16 against primary acute lymphoblastic leukemia cells. Of these, 3 compounds were more potent than resveratrol (IC50=10...
May 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28498435/plumbagin-enhances-trail-induced-apoptosis-of-human-leukemic-kasumi%C3%A2-1-cells-through-upregulation-of-trail-death-receptor-expression-activation-of-caspase-8-and-inhibition-of-cflip
#14
Xiaoyang Kong, Jing Luo, Tongpeng Xu, Yunjiao Zhou, Zengkai Pan, Yinghua Xie, Limin Zhao, Yingting Lu, Xiyao Han, Zhixiong Li, Ligen Liu
Although the patients with t(8;21) acute myeloid leukemia (AML) have a favorable prognosis compared with other non-acute promyelocytic leukemia AML patients, only ~50% patients with this relatively favorable subtype can survive for 5 years and refractory/relapse is common in clinical practice. So it is necessary to find novel agents to treat this type of AML. In this study, the effects and the mechanisms of plumbagin and recombinant soluble tumor necrosis factor‑α-related apoptosis-inducing ligand (rsTRAIL) on leukemic Kasumi‑1 cells were primarily investigated...
May 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28494518/correlates-of-resistance-and-relapse-during-blinatumomab-therapy-for-relapsed-refractory-acute-lymphoblastic-leukemia
#15
Ibrahim Aldoss, Joo Song, Tracey Stiller, Tina Nguyen, Joycelynne Palmer, Margaret O'Donnell, Anthony S Stein, Guido Marcucci, Stephen Forman, Vinod Pullarkat
We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM-ALL). The complete remission (CR) rate was 51%, and 15 (45%) responders underwent allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden (bone marrow blasts >50%) (P=0.02), history of prior EM-ALL (P=0...
May 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28492552/all-trans-retinoic-acid-and-arsenic-trioxide-fail-to-derepress-the-monocytic-differentiation-driver-irf8-in-acute-promyelocytic-leukemia-cells
#16
XiangZhen Liu, Juan Chen, ShanHe Yu, Li Yan, HeZhou Guo, JianMin Dai, Wu Zhang, Jiang Zhu
All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL) cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα). Yet, ~10-15% of APL patients are not cured by ATRA- and ATO-based therapies, and a potential failure of ATRA and ATO in completely reversing PML/RARα-driven oncogenic alterations has not been comprehensively examined. Here we characterized the in vivo primary responses of dysregulated genes in APL cells treated with ATRA and ATO using a GFP-labeled APL model...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28491138/clinicohematological-and-cytogenetic-profile-of-myelodysplastic-syndromes-in-pakistan-compare-and-contrast
#17
Nida Anwar, Aisha Arshad, Muhammad Nadeem, Sana Khurram, Naveena Fatima, Sumaira Sharif, Saira Shan, Tahir Shamsi
BACKGROUND: Myelodysplastic syndromes (MDS) are clonal stem cell disorders exhibiting cytopenias, ineffective hematopoiesis and morphological dysplasia. Bone marrow cytogenetics, inspite of being incorporated as mandatory tool in diagnosis are done less frequently due to limited availability of this technique in Pakistan. The aim of the study was to study baseline clinicohematological and cytogenetic characteristics of patients presenting with de novo MDS. RESULTS: A retrospective cross sectional study was done at National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan from 2010 to 2016...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28490811/high-efficacy-and-safety-of-low-dose-cd19-directed-car-t-cell-therapy-in-51-refractory-or-relapsed-b-acute-lymphoblastic-leukemia-patients
#18
J Pan, J Yang, B Deng, X Zhao, X Zhang, Y Lin, Y Wu, Z Deng, Y Zhang, S Liu, T Wu, P Lu, D Lu, A H Chang, C Tong
Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD(+)) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T cell infusion dosages were initially ranged from 0.05 to 14 × 10(5)/kg and were eventually settled at 1 × 10(5)/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD(+) patients achieved MRD(-)...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28484265/jak-stat-pathway-inhibition-overcomes-il7-induced-glucocorticoid-resistance-in-a-subset-of-human-t-cell-acute-lymphoblastic-leukemias
#19
C Delgado-Martin, L K Meyer, B J Huang, K A Shimano, M S Zinter, J V Nguyen, G A Smith, J Taunton, S S Winter, J R Roderick, M A Kelliher, T M Horton, B L Wood, D Teachey, M L Hermiston
While outcomes for children with T-cell acute lymphoblastic leukemia (T-ALL) have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid (GC) resistance is more common than resistance to other chemotherapies at relapse. Additionally, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor (ETP) T-ALLs as well as in a subset of non-ETP T-ALLs...
May 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28483716/prophylactic-donor-lymphocyte-infusion-dli-followed-by-minimal-residual-disease-and-graft-versus-host-disease-guided-multiple-dlis-could-improve-outcomes-after-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-refractory-relapsed-acute-leukemia
#20
Chen-Hua Yan, Qi-Fa Liu, De-Pei Wu, Xi Zhang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, He Huang, Hai Bai, Fen Huang, Xiao Ma, Xiao-Jun Huang
Patients with refractory/relapsed acute leukemia who have received allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still at a high risk for relapse post-transplant. To investigate the impact of prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease (MRD)-test and graft-versus-host disease (GvHD) guided multiple DLIs to prevent relapse and improve survival in patients with refractory/relapsed acute leukemia who received allo-HSCT. A multicenter prospective study was designed...
May 5, 2017: Biology of Blood and Marrow Transplantation
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