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Elias Jabbour, Maral DerSarkissian, Mei Sheng Duh, Nora McCormick, Wendy Y Cheng, Lisa J McGarry, Ariadne Souroutzidis, Hui Huang, Susan O'Brien, Farhad Ravandi, Hagop M Kantarjian
INTRODUCTION: Complete molecular response (CMR) and 2- and 3-year overall survival (OS) were compared for patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) who had undergone front-line combination chemotherapy plus ponatinib versus combination therapy plus earlier generation tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, and nilotinib). PATIENTS AND METHODS: We identified 26 Ph+ ALL studies: 25 of earlier generation TKIs and 1 of ponatinib...
February 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
Matt Stevenson, Abdullah Pandor, Jean Hamilton, John Stevens, Clare Rowntree, Marrissa Martyn-St James, Andrew Rawdin, Ruth Wong
As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer (Incyte Corporation) of ponatinib (Inclusig® ) to submit evidence of its clinical and cost effectiveness for previously treated Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) and chronic myeloid leukaemia. This paper focusses on Ph+ ALL. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent evidence review group (ERG)...
March 3, 2018: PharmacoEconomics
Abdullah Pandor, Matt Stevenson, John Stevens, Marrissa Martyn-St James, Jean Hamilton, Jenny Byrne, Claudius Rudin, Andrew Rawdin, Ruth Wong
As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures ponatinib (Inclusig® ; Incyte Corporation) to submit evidence for the clinical and cost effectiveness for previously treated chronic myeloid leukaemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). This paper focusses on the three phases of CML: the chronic phase (CP), the accelerated phase (AP) and the blast crisis phase (BP)...
February 26, 2018: PharmacoEconomics
Matthew J Wieduwilt
No abstract text is available yet for this article.
February 20, 2018: Biology of Blood and Marrow Transplantation
Miriam B Herold, Madeline E Giles, Colin J Alexander, Elizabeth M Baggs, Tim J Daniell
Denitrification is a key process responsible for the majority of soil nitrous oxide (N2O) emissions but the influences of pH and cultivation on the soil denitrifier community remain poorly understood. We hypothesised that the abundance and community structure of the total bacterial community and bacterial denitrifiers would be pH sensitive and that nirK and nirS containing denitrifiers would differ in their responses to change in pH and cultivation. We investigated the effect of long-term pH adjusted soils (ranging from pH 4...
February 19, 2018: FEMS Microbiology Letters
Hong-Yan Zhao, Yang Song, Xie-Na Cao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Yuan Kong
Relapse remains one of the major obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) even after allogeneic hematopoietic stem cell transplantation. The persistence of leukemia-propagating cells (LPCs) may lead to the recurrence of Ph + ALL. Using a xenograft assay, LPCs enrichment in the CD34 + CD38 - CD58 - fraction in Ph + ALL was recently identified. A further cohort study indicated that the LPCs phenotype at diagnosis was an independent risk factor for relapse of Ph + ALL...
February 10, 2018: Annals of Hematology
Samira M Abozeid, Eric M Snyder, Timothy Y Tittiris, Charles M Steuerwald, Alexander Y Nazarenko, Janet R Morrow
High-spin Co(II) complexes are promising for development as paraCEST agents (paraCEST = paramagnetic chemical exchange saturation transfer) for magnetic resonance imaging applications. The first examples of Co(II) paraCEST agents with bound water ligands are presented here. Four Co(II) macrocyclic complexes based on 1,4,7-triazacyclononane and containing either pendent alcohol or pendent amide groups were prepared. Two of the macrocycles encapsulate the Co(II) and contain no water ligands as shown by X-ray crystallographic studies, and two complexes have macrocycles with only five ligand donor groups to leave an open coordination site for bound water...
February 7, 2018: Inorganic Chemistry
Satoshi Nishiwaki, Isamu Sugiura, Yasuhiko Miyata, Shigeki Saito, Masashi Sawa, Tetsuya Nishida, Koichi Miyamura, Yachiyo Kuwatsuka, Akio Kohno, Masaaki Yuge, Masanobu Kasai, Hiroatsu Iida, Shingo Kurahashi, Masahide Osaki, Tatsunori Goto, Seitaro Terakura, Makoto Murata, Hiroyoshi Nishikawa, Hitoshi Kiyoi
INTRODUCTION: The prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) has been dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs). Although allogeneic hematopoietic cell transplantation (allo-HCT) is a major treatment option, the role of autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reconsidered, especially in patients who achieved early molecular remission. METHODS AND ANALYSIS: This is a multicenter exploratory study for Ph + ALL patients aged between 55 and 70 years who achieved complete molecular remission within 3 cycles of chemotherapy...
December 2017: Medicine (Baltimore)
Salwa S Saadeh, Mark R Litzow
Allogeneic hematopoietic stem cell transplant (allo-HSCT) has an important role in management of acute lymphoblastic leukemia (ALL). Proper patient selection is central to ensure optimal outcomes. Areas covered: This review covers various aspects of HSCT in ALL patients, including indications, donor selection, conditioning regimens, and post-transplant management. Expert commentary: Allo-HSCT is important in post-remission management of ALL but proper risk-stratification is a major challenge. Incorporation of minimal residual disease (MRD) and molecular testing will improve patient allocation...
January 29, 2018: Expert Review of Hematology
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
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)
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
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
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
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
Here we 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. Data from 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
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
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
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
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
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
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