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https://www.readbyqxmd.com/read/29348129/genomic-cdkn2a-2b-deletions-in-adult-ph-all-are-adverse-despite-allogeneic-stem-cell-transplantation
#1
Heike Pfeifer, Katharina Raum, Sandra Markovic, Verena Nowak, Stephanie Fey, Julia Obländer, Jovita Pressler, Verena Böhm, Monika Brüggemann, Lydia Wunderle, Andreas Hüttmann, Ralph Wäsch, Joachim Beck, Matthias Stelljes, Andreas Viardot, Fabian Lang, Dieter Hoelzer, Wolf-Karsten Hofmann, Hubert Serve, Christel Weiss, Nicola Goekbuget, Oliver G Ottmann, Daniel Nowak
We investigated the role of copy number alterations to refine risk stratification in adult Philadelphia chromosome positive (Ph)+ ALL treated with tyrosine kinase inhibitors (TKI) and allogeneic stem cell transplantation (aSCT). 97 Ph+ ALL patients (median age 41 years, range 18-64 years) within the prospective multicenter GMALL studies 06/99 (n=8) and 07/2003 (n=89) were analysed. All patients received TKI and aSCT in first complete remission (CR1). Copy number analysis was performed with SNP arrays and validated by multiplex ligation-dependent probe amplification (MLPA)...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29338593/expression-and-role-of-granulocyte-macrophage-colony-stimulating-factor-receptor-gm-csfr-and-granulocyte-colony-stimulating-factor-receptor-g-csfr-on-ph-positive-acute-b-lymphoblastic-leukemia
#2
Yong Wu, Ming Tan, Mei-Ling Chen, Yuan-Zhong Chen
OBJECTIVE: We observed that ph + ALL patients administrated with recombinant human G-CSF (rhG-CSF) after intense chemotherapy have presented a trend of disease relapse. Thus, we aim to thoroughly investigate the expression and role of GM-CSFR and G-CSFR on ph + ALL patients. METHOD: SUP-B15, BALL-1 and primary leukemia cells were used in this study. Transcript levels were analyzed by quantitative PCR while cell viability was measured using a CCK-8 assay...
January 17, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29291008/upfront-treatment-with-the-first-and-second-generation-tyrosine-kinase-inhibitors-in-ph-positive-acute-lymphoblastic-leukemia
#3
Guopan Yu, Fang Chen, Changxin Yin, Qifa Liu, Jing Sun, Li Xuan, Zhiping Fan, Qiang Wang, Xiaoli Liu, Qianli Jiang, Dan Xu
The treatment of Ph-positive acute lymphoblastic leukemia (Ph+ ALL) has entranced tyrosine kinase inhibitors (TKIs) era. Currently both imatinib and dasatinib are registered as the front-line treatment for Ph+ ALL, and the other 2nd-generation TKIs are suggested as an alternative for those who failed the first-line treatment. However, it remains unclear who could benefit from the 2nd-generation TKIs as the first-line treatment for Ph+ ALL. In this study we compared the efficacy and safety of the 1st and 2nd-generation TKIs in the front-line treatment of Ph+ ALL and found a trend toward better disease-free survival (DFS) in the 2nd-generation TKIs group, though no significant difference in early response and long-term survival between the two groups...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287395/bioaccessibility-of-four-calcium-sources-in-different-whey-based-dairy-matrices-assessed-by-in-vitro-digestion
#4
Lucie Lorieau, Linda Le Roux, Frédéric Gaucheron, Amandine Ligneul, Etienne Hazart, Didier Dupont, Juliane Floury
Numerous calcium sources are available to enrich food, but their behavior during digestion is still unknown. This study focused on the influence of the gastro-intestinal pH, the food structure and the calcium source on the bioaccessibility of the nutrient. Four calcium sources were studied: calcium carbonate, calcium citrate malate, calcium phosphate and calcium bisglycinate. These were added to dairy matrices, containing cream and whey proteins, of different forms (liquid or gel). The kinetics of solubility and ionic calcium concentration during in vitro digestion were studied, as function of gastro-intestinal pH...
April 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29284366/pepsi%C3%A2-or-coke%C3%A2-influence-of-acid-on-dasatinib-absorption
#5
Randall W Knoebel, Richard A Larson
Dasatinib is a second generation ABL kinase inhibitor used in the management of chronic myeloid leukemia or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Dasatinib's bioavailability is highly dependent on gastric pH. When proton-pump inhibitors (PPIs) are co-administered with dasatinib, absorption is significantly reduced. Cola intake at the time of drug administration has been demonstrated to lead to relevant increases in the bioavailability for other acid labile drugs during PPI treatment...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29247779/allogeneic-stem-cell-transplantation-versus-tyrosine-kinase-inhibitors-combined-with-chemotherapy-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#6
Jing Wang, Qian Jiang, Lan-Ping Xu, Xiao-Hui Zhang, Huan Chen, Ya-Zhen Qin, Guo-Rui Ruan, Hao Jiang, Jin-Song Jia, Ting Zhao, Kai-Yan Liu, Bin Jiang, Xiao-Jun Huang
OBJECTIVE: To compare outcomes between the tyrosine kinase inhibitors (TKIs) plus chemotherapy regimen and allogeneic hematopoietic stem cell transplantation (transplantation cohort) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) and explore factors associated with prognosis. METHODS: Data of 145 Ph+ALL patients were analyzed retrospectively. Patients were treated with imatinib plus chemotherapy, and then transplantation or continuous TKIs with chemotherapy based on patient preference...
December 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29236701/anti-leukemic-activity-of-bortezomib-and-carfilzomib-on-b-cell-precursor-all-cell-lines
#7
Kazuya Takahashi, Takeshi Inukai, Toshihiko Imamura, Mio Yano, Chihiro Tomoyasu, David M Lucas, Atsushi Nemoto, Hiroki Sato, Meixian Huang, Masako Abe, Keiko Kagami, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Jiro Kikuchi, Yusuke Furukawa, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Kanji Sugita
Prognosis of childhood acute lymphoblastic leukemia (ALL) has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ), a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response...
2017: PloS One
https://www.readbyqxmd.com/read/29233926/targeting-cdk6-and-bcl2-exploits-the-myb-addiction-of-ph-acute-lymphoblastic-leukemia
#8
Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A Mariani, Sankar Addya, Paolo Fortina, Luke F Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta
Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1-dependent and -independent mechanisms. Newly developed TKI can target Ph+ ALL cells with BCR-ABL1-dependent resistance; however, overcoming BCR-ABL1-independent mechanisms of resistance remains challenging because transcription factors (TF), which are difficult to inhibit, are often involved...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29214878/combination-of-ikzf1-deletion-and-early-molecular-response-show-significant-roles-on-prognostic-stratification-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-patients
#9
He Li, Wanhua Zhang, Pu Kuang, Yuanxin Ye, Jinjun Yang, Yang Dai, Xiaojun Lu, Yuhuan Zheng, Ting Liu
We retrospectively analyzed the samples collected from 66 patients with Ph+ALL enrolled on ChiCTR-TNRC-09000309 clinical trial. CR rate was 95.5%, and estimated 2-year OS and DFS were 51.7 ± 11.7% and 26.9 ± 11.6%, 3-year OS and DFS were 31.6 ± 12.0% and 23.4 ± 11.6%. By combining IKZF1 deletion and early molecular responses, we redefined the patients as low, intermediate, and high risk 3 groups separately. Patients with double negative in IKZF1 and early molecular response experienced significant superior survival, while patients with double positive would have the worst outcome, and patients who were one or the other with IKZF1 deletion or MRD status had intermediate outcome...
December 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29212977/-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-complicated-by-concomitant-achromobacter-xylosoxidans-and-corynebacterium-striatum-bacteremia-following-allogeneic-hematopoietic-stem-cell-transplantation
#10
Yuta Katayama, Kouhei Kyo, Koji Iwato, Takeshi Okatani, Ryota Imanaka, Mitsuhiro Itagaki, Shinya Katsutani, Hideki Asaoku
A 54-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) underwent hematopoietic stem cell transplantation from an HLA-matched sibling. Subsequently, she suffered from chronic graft versus host disease (GvHD) and received medical treatment. Fever developed on day 697 and resulted in a shock state at 10 h after the visit. Achromobacter xylosoxidans was detected in the initial blood culture on day 699. General conditions exacerbated even after the start of meropenem hydrate (MEPM, Meropen®) administration, with Corynebacterium striatum detected as an additional species in the initial blood culture on day 701...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29188580/10-year-complete-remission-in-a-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-patient-using-imatinib-without-high-intensity-chemotherapy-or-allogeneic-stem-cell-transplantation
#11
Katsumichi Fujimaki, Yukako Hattori, Hideaki Nakajima
The outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) has improved with the use of tyrosine kinase inhibitors, such as imatinib and dasatinib. We report a 63-year-old woman with Ph-ALL who maintained complete remission for 10 years using imatinib without high-intensity chemotherapy or allogeneic stem cell transplantation. She underwent induction therapy with imatinib plus prednisolone and achieved complete remission by day 53. Imatinib was continued until 103 months, when it was stopped in response to renal dysfunction; however, the patient continued to exhibit molecular remission at 120 months...
November 29, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29179113/effects-of-ph-dynamics-on-solidification-stabilization-of-municipal-solid-waste-incineration-fly-ash
#12
Yahaya Yakubu, Jun Zhou, Duan Ping, Zhu Shu, Yun Chen
Fly ash (FA), a product of municipal solid waste incineration (MSWI), has been classified as a kind of hazardous waste due to its high content of heavy metals. FA may be reused in the construction industry or disposed of at landfill sites, and thus poses threats to both the environment and human health. This study sought to establish a scientific basis for accurate selection of suitable pH storage conditions for the FA. We evaluated the potential of MSWI FA sample from the Xinghuo waste incineration power plant, Wuhan, to solidify/stabilize the heavy metal (Cu, Pb, Zn, Cr, Cd, As and Mn) contents, when leached under different pH conditions...
November 24, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/29164981/successful-treatment-of-ph-all-with-hematopoietic-stem-cell-transplantation-from-the-same-hla-haploidentical-related-donor-of-previous-liver-transplantation
#13
Kensuke Sasaki, Yasuo Mori, Goichi Yoshimoto, Teppei Sakoda, Koji Kato, Kyoko Inadomi, Kenjiro Kamezaki, Katsuto Takenaka, Hiromi Iwasaki, Takahiro Maeda, Toshihiro Miyamoto, Koichi Akashi
No abstract text is available yet for this article.
November 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29132472/-research-progress-in-ph-like-childhood-acute-lymphoblastic-leukemia
#14
Xue Tang, Xia Guo
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a subtype of B-lineage ALL (B-ALL) that displays a gene expression profile (GEP) similar to Philadelphia chromosome-positive ALL (Ph(+) ALL). It has a diverse range of genetic alterations that activate cytokine receptor genes and kinase signaling pathways, frequently accompanied by abnormal transcription factors related to lymphatic development. Children with Ph-like ALL account for 15% of children with high-risk B-ALL. It has adverse clinical features and a poor prognosis...
November 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29115339/electro-oxidation-of-a-cobalt-based-steel-in-lioh-a-non-noble-metal-based-electro-catalyst-suitable-for-durable-water-splitting-in-an-acidic-milieu
#15
Helmut Schäfer, Karsten Küpper, Klaus Müller-Buschbaum, Diemo Daum, Martin Steinhart, Joachim Wollschläger, Ulrich Krupp, Mercedes Schmidt, Weijia Han, Johannes Stangl
The use of proton exchange membrane (PEM) electrolyzers is the method of choice for the conversion of solar energy when frequently occurring changes of the current load are an issue. However, this technique requires electrolytes with low pH. All oxygen evolving electrodes working durably and actively in acids contain IrOx. Due to their scarcity and high acquisition costs, noble elements like Pt, Ru and Ir need to be replaced by earth abundant elements. We have evaluated a cobalt containing steel for use as an oxygen-forming electrode in H2SO4...
November 23, 2017: Nanoscale
https://www.readbyqxmd.com/read/29079599/predictive-value-of-mrd-in-ph-all-treated-with-imatinib-in-the-esphall-study-based-on-ig-tr-and-bcr-abl1-methodologies
#16
Giovanni Cazzaniga, Paola De Lorenzo, Julia Alten, Silja Röttgers, Jeremy Hancock, Vaskar Saha, Anders Castor, Hans O Madsen, Virginie Gandemer, Hélène Cavé, Veronica Leoni, Rolf Köhler, Giulia M Ferrari, Kirsten Bleckmann, Rob Pieters, Vincent Van der Velden, Jan Stary, Jan Zuna, Gabriele Escheric, Udo Zur Stadt, Maurizio Aricò, Valentino Conter, Martin Schrappe, Maria Grazia Valsecchi, Andrea Biondi
The prognostic value of Minimal Residual Disease in Ph+ childhood acute lymphoblastic leukemia treated with tyrosine kinase inhibitors is not fully established. We detected MRD by RQ-PCR of rearranged immunoglobulin/T-cell receptor genes and/or BCR/ABL1 fusion transcript to investigate its predictive value in patients receiving BFM high risk therapy and post induction intermittent imatinib (EsPhALL study). MRD was monitored after induction (TP1), consolidation Phase IB (TP2), HR Blocks, reinductions, end of therapy...
October 27, 2017: Haematologica
https://www.readbyqxmd.com/read/29050693/how-should-we-treat-older-adults-with-ph-adult-all-and-what-novel-approaches-are-being-investigated
#17
REVIEW
Matthew J Wieduwilt
Treatment of older patients with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia presents unique challenges. Advanced age, comorbidities, high treatment-related death rates with traditional chemotherapy, and relapse combine to yield poor survival. Reduced-intensity induction with BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) and corticosteroids yields CR rates 96-100% with no induction mortality but relapse is nearly certain without effective consolidation. Few clinical trials provide guidance on optimal consolidation for older Ph+ ALL...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29050692/which-tyrosine-kinase-inhibitor-should-we-use-to-treat-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#18
REVIEW
Nicholas J Short, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi
The incorporation of tyrosine kinase inhibitors (TKIs) into chemotherapy regimens has significantly improved the long-term survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Successive generations of TKIs with increased potency against BCR-ABL and broader spectrum of activity against ABL kinase domain mutations have led to incremental improvements in the outcomes of patients with this disease. In particular, ponatinib, a potent pan-BCR-ABL TKI capable of overcoming the T315I mutation, holds significant promise in the treatment of Ph+ ALL, although the potential cardiovascular toxicity of this agent remains a concern...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29047122/the-presence-of-philadelphia-chromosome-does-not-confer-poor-prognosis-in-adult-pre-b-acute-lymphoblastic-leukaemia-in-the-tyrosine-kinase-inhibitor-era-a-surveillance-epidemiology-and-end-results-database-analysis
#19
Igwe J Igwe, Dongyun Yang, Akil Merchant, Noah Merin, George Yaghmour, Kevin Kelly, Giridharan Ramsingh
The BCR-ABL1 fusion gene is caused by a translocation between chromosomes 9 and 22, resulting in an abnormal chromosome 22 (Philadelphia chromosome; Ph). Prior to the introduction of tyrosine kinase inhibitors (TKI), the presence of BCR-ABL1 conferred a poor prognosis in patients with acute lymphoblastic leukaemia (ALL). We compared the survival of Ph+ and Ph-ALL during the period when TKIs were universally available in the US for Ph+ALL, using a Surveillance, Epidemiology, and End Results (SEER) Database analysis...
October 18, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29046900/us-intergroup-study-of-chemotherapy-plus-dasatinib-and-allogeneic-stem-cell-transplant-in-philadelphia-chromosome-positive-all
#20
Farhad Ravandi, Megan Othus, Susan M O'Brien, Stephen J Forman, Chul S Ha, Jeffrey Y C Wong, Martin S Tallman, Elisabeth Paietta, Janis Racevskis, Geoffrey L Uy, Mary Horowitz, Naoko Takebe, Richard Little, Uma Borate, Partow Kebriaei, Laura Kingsbury, Hagop M Kantarjian, Jerald P Radich, Harry P Erba, Frederick R Appelbaum
This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100...
December 27, 2016: Blood Advances
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