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https://www.readbyqxmd.com/read/28535095/managing-cns-disease-in-adults-with-acute-lymphoblastic-leukemia
#1
Richard A Larson
The central nervous system (CNS) is an important site of involvement by acute lymphoblastic leukemia (ALL) in adults. The prevalence is sufficiently high that prophylactic treatment is routinely given to this sanctuary site in order to eradicate occult disease that might otherwise lead to a relapse. A lumbar puncture should be routinely performed in all newly diagnosed patients with ALL. The risks of CNS leukemia vary by phenotype and genotype. Preventive treatment of the CNS during post-remission therapy has become an integral part of all current ALL treatment protocols...
May 23, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28535084/impact-of-initial-csf-findings-on-outcome-among-patients-with-national-cancer-institute-standard-and-high-risk-b-cell-acute-lymphoblastic-leukemia-a-report-from-the-children-s-oncology-group
#2
Naomi Winick, Meenakshi Devidas, Si Chen, Kelly Maloney, Eric Larsen, Leonard Mattano, Michael J Borowitz, Andrew Carroll, Julie M Gastier-Foster, Nyla A Heerema, Cheryl Willman, Brent Wood, Mignon L Loh, Elizabeth Raetz, Stephen P Hunger, William L Carroll
Purpose To determine the prognostic significance of blasts, and of white and red blood cells, in CSF samples at diagnosis of acute lymphoblastic leukemia (ALL), a uniform CSF and risk group classification schema was incorporated into Children's Oncology Group B-cell ALL (B-ALL) clinical trials. Methods CSF status was designated as follows: CNS1, no blasts; CNS2a to 2c, < 5 WBCs/μL and blasts with/without ≥ 10 RBCs/μL or ≥ 5 WBCs/μL plus blasts, with WBCs ≥ 5 times the number of RBCs; CNS3a to 3c, ≥ 5 WBCs/μL plus blasts with/without ≥ 10 RBCs/μL or clinical signs of CNS disease...
May 23, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28534526/impact-of-genetic-polymorphisms-determining-leukocyte-neutrophil-count-on-chemotherapy-toxicity
#3
S J Glisovic, Y D Pastore, V Gagne, M Plesa, C Laverdière, J M Leclerc, D Sinnett, M Krajinovic
Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications are directly related to the depth and duration of neutropenia. Recent genome-wide association studies identified variants in DARC and CXCL2 genes, and in ORMDL3-GSDMA-CSF3 locus on chromosome 17q21 that influence white blood cell and neutrophil counts in healthy individuals. To investigate whether polymorphisms in these loci in conjunction with chemotherapy may modulate risk of treatment complications, we analyzed 21 SNPs across these genes for an association with chemotherapy-related neutropenia and infection in 286 Caucasian children with acute lymphoblastic leukemia...
May 23, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28534383/in-vitro-anticancer-activity-and-cytotoxicity-screening-of-phytochemical-extracts-from-selected-traditional-chinese-medicinal-plants
#4
Chao Liang, Hui Pan, Haizhou Li, Yang Zhao, Yang Feng
PURPOSE: The purpose of this study was to evaluate the anticancer activity of 10 selected traditional Chinese medicinal plants on 4 cancer cell lines, namely MCF-7 (breast carcinoma), BALL-1 (acute lymphoblastic leukemia), Huh-7 (hepatocellular carcinoma), HeLa (cervical carcinoma) and their cytotoxicity on a normal cell line, namely MCF-10A (non-tumorigenic mammary epithelial line), about which there were few reports previously. METHODS: Six phytochemical extracts, namely petroleum ether extract (PEE), chloroform extract (CE), ethyl acetate extract (EAE), n-butanol extract (BE), the remainder after extraction (RE) and water extract (WE) from each plant were prepared...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28534346/the-use-of-inexpensive-broad-spectrum-lower-toxicity-therapeutics-in-chronic-lymphocytic-leukemia
#5
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/28534184/evaluation-of-cardiovascular-ischemic-event-rates-in-dasatinib-treated-patients-using-standardized-incidence-ratios
#6
Giuseppe Saglio, Philipp le Coutre, Jorge Cortes, Jiří Mayer, Philip Rowlings, François-Xavier Mahon, Glenn Kroog, Kyna Gooden, Milayna Subar, Neil P Shah
With high survival rates for chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs), emerging consequences, such as arterial ischemic events, require consideration when evaluating treatment options. Cardiovascular ischemic event incidence in clinical trials was evaluated in 2712 dasatinib-treated patients with Philadelphia chromosome-positive (Ph+) leukemias from 11 first- and second-line trials (pooled), newly diagnosed CML patients treated with dasatinib or imatinib (DASISION), and prostate cancer patients treated with dasatinib or placebo plus docetaxel/prednisone (READY)...
May 22, 2017: Annals of Hematology
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
#7
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/28533538/proteomic-analysis-of-jak2v617f-induced-changes-identifies-potential-new-combinatorial-therapeutic-approaches
#8
S Pearson, A J K Williamson, R Blance, T C P Somervaille, S Taylor, N Azadbakht, A D Whetton, A Pierce
In excess of 90% of patients with polycythemia vera express a mutated form of JAK2, JAK2V617F. Such aberrant proteins offer great potential for the treatment of these diseases however inhibitors to JAK2 have had limited success in the clinic in terms of curing the disease. To understand the effects of this oncogene in hematopoietic cells with the aim of improving treatment strategies we undertook a systematic evaluation of the effects of JAK2V617F expression using proteomics. The effects of JAK2V617F on over 5000 proteins and 2000 nuclear phosphopeptides sites were relatively quantified using either SILAC or eight channel iTRAQ mass spectrometry...
May 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28533390/prognostic-and-biological-significance-of-the-proangiogenic-factor-egfl7-in-acute-myeloid-leukemia
#9
Dimitrios Papaioannou, Changxian Shen, Deedra Nicolet, Betina McNeil, Marius Bill, Malith Karunasiri, Matthew H Burke, Hatice Gulcin Ozer, Selen A Yilmaz, Nina Zitzer, Gregory K Behbehani, Christopher C Oakes, Damian J Steiner, Guido Marcucci, Bayard L Powell, Jonathan E Kolitz, Thomas H Carter, Eunice S Wang, Krzysztof Mrózek, Carlo M Croce, Michael A Caligiuri, Clara D Bloomfield, Ramiro Garzon, Adrienne M Dorrance
Epithelial growth factor-like 7 (EGFL7) is a protein that is secreted by endothelial cells and plays an important role in angiogenesis. Although EGFL7 is aberrantly overexpressed in solid tumors, its role in leukemia has not been evaluated. Here, we report that levels of both EGFL7 mRNA and EGFL7 protein are increased in blasts of patients with acute myeloid leukemia (AML) compared with normal bone marrow cells. High EGFL7 mRNA expression associates with lower complete remission rates, and shorter event-free and overall survival in older (age ≥60 y) and younger (age <60 y) patients with cytogenetically normal AML...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533061/comparison-of-autologous-and-unrelated-transplants-for-cytogenetically-normal-acute-myeloid-leukemia
#10
Motonori Mizutani, Akiyoshi Takami, Masahiko Hara, Shohei Mizuno, Masamitsu Yanada, Takaaki Chou, Hitoji Uchiyama, Kazuteru Ohashi, Toshihiro Miyamoto, Yukiyasu Ozawa, Osamu Imataki, Naoki Kobayashi, Naoyuki Uchida, Heiwa Kanamori, Tomohiko Kamimura, Tetsuya Eto, Makoto Onizuka, Junji Tanaka, Yoshiko Atsuta, Shingo Yano
Allogeneic stem cell transplantation (SCT) from an HLA-matched sibling donor (MSD) is a post-remission treatment that offers a potential cure for adults with cytogenetically normal acute myeloid leukemia in their first complete remission (CN-AML/CR1). However, the best alternative in the absence of an MSD remains unclear. The aim of this study was to retrospectively compare the outcomes of autologous peripheral blood stem cell transplantation (auto-PBSCT; n = 177) to those of allogeneic bone marrow transplantation from an HLA-matched unrelated donor (MUD-BMT; n = 173) in adult patients with CN-AML/CR1...
May 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28531166/-epiafzelechin-protects-against-ovariectomy-induced-bone-loss-in-adult-mice-and-modulate-osteoblastic-and-osteoclastic-functions-in-vitro
#11
Ka-Chun Wong, Sisi Cao, Xiaoli Dong, Man-Chun Law, Tak-Hang Chan, Man-Sau Wong
The present study was designed to characterize the bone protective effects of (-)-epiafzelechin (EAF), a flavan-3-ol, in mature ovariectomized mice model and its ability to stimulate osteoblastic activity and inhibit osteoclastic activity. Mature C57BL/6 mice (three to four months old) were either ovariectomised (OVX) or sham-operated and subjected to treatment (vehicle, 17β-oestradiol (E2, 200 μg/kg/day) or EAF (500 μg/kg/day) orally for six weeks. EAF and E2 significantly reduced urinary calcium (Ca) excretion, serum osteocalcin (OCN), and urinary deoxy-pyridinoline (DPD); increased bone mineral density (BMD); and improved micro-architectural properties in OVX mice...
May 22, 2017: Nutrients
https://www.readbyqxmd.com/read/28530852/long-term-risk-of-subsequent-malignant-neoplasms-after-treatment-of-childhood-cancer-in-the-dcog-later-study-cohort-role-of-chemotherapy
#12
Jop C Teepen, Flora E van Leeuwen, Wim J Tissing, Eline van Dulmen-den Broeder, Marry M van den Heuvel-Eibrink, Helena J van der Pal, Jacqueline J Loonen, Dorine Bresters, Birgitta Versluys, Sebastian J C M M Neggers, Monique W M Jaspers, Michael Hauptmann, Margriet van der Heiden-van der Loo, Otto Visser, Leontien C M Kremer, Cécile M Ronckers
Purpose Childhood cancer survivors (CCSs) are at increased risk for subsequent malignant neoplasms (SMNs). We evaluated the long-term risk of SMNs in a well-characterized cohort of 5-year CCSs, with a particular focus on individual chemotherapeutic agents and solid cancer risk. Methods The Dutch Childhood Cancer Oncology Group-Long-Term Effects After Childhood Cancer cohort includes 6,165 5-year CCSs diagnosed between 1963 and 2001 in the Netherlands. SMNs were identified by linkages with the Netherlands Cancer Registry, the Dutch Pathology Registry, and medical chart review...
May 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28530540/novel-n-mustard-benzimidazoles-benzothiazoles-hybrids-synthesis-and-anticancer-evaluation
#13
Dilip P Detroja, Tai-Lin Chen, Yi-Wen Lin, Tsai-Yi Yen, Ming-Hsi Wu, Tung-Hu Tsai, Krunal Maheriya, Rajesh Kakadiya, Te-Chang Lee, Anamik Shah, Tsann-Long Su
BACKGROUND: Bendamustine, an N-mustard-benzoimidazole hybrid conjugate, was recently approved for the treatment of chronic lymphocytic leukemia. However, the short half-life of bendamustine may limit its clinical applications. OBJECTIVE: The purpose of this study is to design and synthesize compounds with a more favorable pharmacokinetic profile. METHODS: We synthesized a series of hybrid molecules comprising a phenyl N-mustard moiety and benzothiazole or benzimidazole scaffold linked via an ureido linker and evaluated their antitumor activity and plasma stability...
May 22, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28529924/regulation-of-cancer-cell-responsiveness-to-ionizing-radiation-treatment-by-cyclic-amp-response-element-binding-nuclear-transcription-factor
#14
REVIEW
Francesca D'Auria, Lucia Centurione, Maria Antonietta Centurione, Antonio Angelini, Roberta Di Pietro
Cyclic AMP response element binding (CREB) protein is a member of the CREB/activating transcription factor (ATF) family of transcription factors that play an important role in the cell response to different environmental stimuli leading to proliferation, differentiation, apoptosis, and survival. A number of studies highlight the involvement of CREB in the resistance to ionizing radiation (IR) therapy, demonstrating a relationship between IR-induced CREB family members' activation and cell survival. Consistent with these observations, we have recently demonstrated that CREB and ATF-1 are expressed in leukemia cell lines and that low-dose radiation treatment can trigger CREB activation, leading to survival of erythro-leukemia cells (K562)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28529312/prognostic-impact-of-ikzf1-deletions-in-association-with-vincristine-dexamethasone-pulses-during-maintenance-treatment-of-childhood-acute-lymphoblastic-leukemia-on-trial-all-bfm-95
#15
L Hinze, A Möricke, M Zimmermann, S Junk, G Cario, E Dagdan, C P Kratz, V Conter, M Schrappe, M Stanulla
Leukemia accepted article preview online, 22 May 2017. doi:10.1038/leu.2017.154.
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28529308/assessing-the-thrombotic-risk-of-patients-with-essential-thrombocythemia-in-the-genomic-era
#16
REVIEW
L Falchi, H M Kantarjian, S Verstovsek
The molecular characterization of myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), has enabled deeper understanding of their pathogenesis. A driver lesion, namely, Janus kinase (JAK)2V617F, calreticulin (CALR) or myeloproliferative leukemia (MPL) gene mutation can be identified in the vast majority of patients. Each of these mutations is associated with distinct clinical features and may modulate the patients' clinical course, risk of complications, including vascular events, and survival...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28529307/genetic-deletion-of-sost-or-pharmacological-inhibition-of-sclerostin-prevent-multiple-myeloma-induced-bone-disease-without-affecting-tumor-growth
#17
J Delgado-Calle, J Anderson, M D Cregor, K W Condon, S A Kuhstoss, L I Plotkin, T Bellido, G D Roodman
Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl) levels, an osteocyte-derived inhibitor of Wnt/β-catenin signaling, are elevated in MM patient sera and are increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28529020/nosocomial-legionellosis-and-invasive-aspergillosis-in-a-child-with-t-lymphoblastic-leukemia
#18
Rhoikos Furtwängler, Uwe Schlotthauer, Barbara Gärtner, Norbert Graf, Arne Simon
Invasive aspergillosis of the lungs and the central nervous system and Legionella pneumophilia serotype 1 infection of the lungs were diagnosed in a 22-month old child during inpatient induction treatment for T-lymphoblastic leukemia. Environmental investigations i.e. samples from the hospital water system did not reveal any Legionella. The patient may have been exposed to waterborne pathogens despite terminal water filtration due to a technical device to release residual tap water from the hose after showering...
May 13, 2017: International Journal of Hygiene and Environmental Health
https://www.readbyqxmd.com/read/28528702/detailed-characterization-of-mesenchymal-stem-stromal-cells-from-a-large-cohort-of-aml-patients-demonstrates-a-definitive-link-to-treatment-outcomes
#19
Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup...
May 18, 2017: Stem Cell Reports
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
#20
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
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