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https://www.readbyqxmd.com/read/28534346/the-use-of-inexpensive-broad-spectrum-lower-toxicity-therapeutics-in-chronic-lymphocytic-leukemia
#1
Goran Marjanovic
The use of new and highly efficient targeted therapies for chronic lymphocytic leukemia (CLL) is costly and out of reach for many health care systems. On the other hand, in recent years, few inexpensive, broad-spectrum low-toxicity therapeutics have proven to be effective both in the preclinical and clinical settings. In early-stage CLL, the use of 2000 mg of epigallocatechin-3-gallate (EGCG) from the green tea extract twice a day was able to reduce the absolute leukocyte count. Supplementation of >2000 IU/day of Vitamin D in early low-risk CLL patients is able to delay disease progression and postpone the moment of initiation of the first treatment...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of 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
#2
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
#3
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/28527985/long-term-follow-up-and-impact-of-comorbidity-prior-to-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-relapsed-or-refractory-aml-lessons-learned-from-the-prospective-bridge-trial-clofarabine-salvage-therapy-prior-to-allogeneic-transplantation
#4
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) 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 prior to HSCT in patients with r/r AML. Here, we report the long-term follow up of this Phase II, multi-center trial and exploratory analyses on the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range 40 - 75) were enrolled...
May 17, 2017: Biology of Blood and Marrow Transplantation
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/28523104/3-aroyl-1-4-diarylpyrroles-inhibit-chronic-myeloid-leukemia-cell-growth-through-an-interaction-with-tubulin
#6
Giuseppe La Regina, Ruoli Bai, Antonio Coluccia, Valeria Famiglini, Sara Passacantilli, Valentina Naccarato, Giorgio Ortar, Carmela Mazzoccoli, Vitalba Ruggieri, Francesca Agriesti, Claudia Piccoli, Tiziana Tataranni, Marianna Nalli, Andrea Brancale, Stefania Vultaggio, Ciro Mercurio, Mario Varasi, Concetta Saponaro, Sara Sergio, Michele Maffia, Addolorata Maria Luce Coluccia, Ernest Hamel, Romano Silvestri
We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation...
May 11, 2017: ACS Medicinal Chemistry Letters
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
#7
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
#8
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/28515252/chronic-lymphocytic-leukemia-individualizing-treatment-approach
#9
Andrew D Zelenetz
A host of new therapies are now available for treating patients with chronic lymphocytic leukemia (CLL) in both the upfront and relapsed or refractory settings. Although the optimal use of these agents is still being defined, established and emerging prognostic markers aid in the selection of appropriate treatment with the best chance of success. At the NCCN 22nd Annual Conference, Dr. Andrew Zelenetz discussed the role of the CLL-International Prognostic Index for risk stratification, reviewed optimal first-line therapy options, and then presented updated clinical trial data on the novel agents being used in the relapsed or refractory setting...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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/28494631/learning-from-the-failures-of-drug-discovery-in-b-cell-non-hodgkin-lymphomas-and-perspectives-for-the-future-chronic-lymphocytic-leukemia-and-diffuse-large-b-cell-lymphoma-as-two-ends-of-a-spectrum-in-drug-development
#17
Boris Kubuschok, Martin Trepel
Despite substantial recent advances, there is still an unmet need for better therapies in B-cell non Hodgkin lymphomas (B-NHL), especially in relapsed or refractory disease. Many novel targeted drugs have been developed based on a better molecular understanding of B-NHL. Areas covered: This article focuses on chronic lymphocytic leukemia (CLL) as a representative for indolent lymphomas and paradigmatic for the tremendous progress in treating B-NHL on the one hand and diffuse large B-cell lymphoma (DLBCL) as a representative for aggressive lymphomas and paradigmatic for many unsolved problems in lymphoma treatment on the other hand...
May 12, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28494518/correlates-of-resistance-and-relapse-during-blinatumomab-therapy-for-relapsed-refractory-acute-lymphoblastic-leukemia
#18
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
#19
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/28492339/venetoclax-for-the-treatment-of-patients-with-chronic-lymphocytic-leukemia
#20
Jennifer Crombie, Matthew S Davids
Venetoclax is a potent, selective inhibitor of BCL-2, a key regulator of the intrinsic pathway of apoptosis. In preclinical studies, venetoclax bound to BCL-2 with high affinity and rapidly induced apoptosis in chronic lymphocytic leukemia (CLL) cells. In early-phase clinical trials in CLL, venetoclax treatment led to tumor lysis syndrome in some patients with a large tumor burden, but this risk was subsequently mitigated by a revised study design that included lower initial dosing with intrapatient dose ramp-up and close tumor lysis syndrome monitoring and prophylaxis...
May 11, 2017: Future Oncology
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