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https://www.readbyqxmd.com/read/27932374/discontinuation-of-dasatinib-or-nilotinib-in-chronic-myeloid-leukemia-interim-analysis-of-the-stop-2g-tki-study
#1
Delphine Rea, Franck E Nicolini, Michel Tulliez, François Guilhot, Joelle Guilhot, Agnès Guerci-Bresler, Martine Gardembas, Valérie Coiteux, Gaelle Guillerm, Laurence Legros, Gabriel Etienne, Jean-Michel Pignon, Bruno Villemagne, Martine Escoffre-Barbe, Jean-Christophe Ianotto, Aude Charbonnier, Hyacinthe Johnson-Ansah, Marie-Pierre Noel, Philippe Rousselot, François-Xavier Mahon
STOP 2G-TKI is a multicenter observational study designed to evaluate 2(nd) generation (2G)-tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML). Patients receiving 1(st) or subsequent line dasatinib or nilotinib who stopped therapy after at least 3 years of TKI treatment and in molecular response 4.5 (MR4.5) with undetectable BCR-ABL1 transcripts for the 2 preceding years at least were eligible for inclusion. This interim analysis reports outcomes of 60 patients with a minimum follow-up of 12 months (median 47, range; 12-65)...
December 8, 2016: Blood
https://www.readbyqxmd.com/read/27932187/successful-t-cell-replete-hematopoietic-stem-cell-boost-without-conditioning-for-late-graft-failure
#2
Y Tsutsumi, T Tateno, S Ito, S Shiratori, T Teshima
Late graft failure is a rare but significant complication after allogeneic stem cell transplantation, which is often complicated by severe infections. We report a case of late graft failure, which was successfully treated with a T-cell replete hematopoietic stem cell boost without conditioning that induced rapid engraftment and relieved the patient of infection. Discontinuation of immunosuppressants and nilotinib administration suppressed the host cells. Achieving full donor chimerism allowed us to administer a peripheral blood stem cell boost without conditioning...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27928806/-molecular-mechanism-of-gastrointestinal-stromal-tumors-and-progress-in-drug-research
#3
Jian Li
The functional mutation of c-kit and platelet-derived growth factor receptor α (PDGFRA) which encode proto-oncogene receptor tyrosine kinase are the crucial pathogeneses of gastrointestinal stromal tumors(GISTs). 80%-85% c-kit gene mutation including exon 11,exon 9,exon 13,exon 17 and 5%-10% PDGFRA gene mutation such as exon 18, exon 12 are examined in GISTs. Neither of c-kit or PDGFRA gene mutation are called wide type GISTs. The pathogeneses of wild type GISTs are not clear. The deficiency of succinate dehydrogenase B(SDHB)-related insulin-like growth factor 1(IGF-1R) activation, BRAF gene mutation and neurofibromatosis type 1 may be related to progression of wild type GISTs...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27904116/symptomatic-acute-pancreatitis-induced-by-nilotinib-a-report-of-two-cases
#4
Toshiki Yamada, Yasuhito Nannya, Masahito Shimizu, Mitsuru Seishima, Hisashi Tsurumi
Nilotinib is a selective tyrosine kinase inhibitor for the treatment of Philadelphia chromosome-positive leukemias. An elevation of the pancreatic enzyme level is one of the major adverse events associated with nilotinib, but whether or not nilotinib induces symptomatic pancreatitis remains to be elucidated. The cases of two chronic myeloid leukemia patients treated with nilotinib who developed symptomatic acute pancreatitis on the third and fifth day of nilotinib administration are herein presented. Since both patients had no other etiologies for pancreatitis, nilotinib was considered to be the causal agent...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27901368/second-line-small-molecule-therapy-options-for-treating-chronic-myeloid-leukemia
#5
Matteo Molica, Fulvio Massaro, Massimo Breccia
Approximately 33% of chronic myeloid leukemia (CML) patients discontinue treatment with imatinib in the long-term due to resistance and/or intolerance. Second-generation tyrosine kinase inhibitors (TKIs) (dasatinib, nilotinib, bosutinib) and third-generation (ponatinib) have added complexity to the treatment paradigm for this disease. Areas covered: Second generation TKIs, approved as second-line treatment in all phases of the disease, are highly effective in patients resistant to and/or intolerant to imatinib and are extremely active against all the resistant BCR-ABL1 mutations, with the exception of T3151...
December 9, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27890073/switching-to-nilotinib-versus-imatinib-dose-escalation-in-patients-with-chronic-myeloid-leukaemia-in-chronic-phase-with-suboptimal-response-to-imatinib-lasor-a-randomised-open-label-trial
#6
Jorge E Cortes, Carmino Antonio De Souza, Manuel Ayala, Jose Luis Lopez, Eduardo Bullorsky, Sandip Shah, Xiaojun Huang, K Govind Babu, Kudrat Abdulkadyrov, José Salvador Rodrigues de Oliveira, Zhi-Xiang Shen, Tomasz Sacha, Israel Bendit, Zhizhou Liang, Tina Owugah, Tomasz Szczudlo, Sadhvi Khanna, Rafik Fellague-Chebra, Philipp D le Coutre
BACKGROUND: Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib. METHODS: We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries)...
December 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27890072/nilotinib-against-high-dose-imatinib-for-salvage-therapy-of-chronic-myeloid-leukaemia
#7
Simona Soverini, Michele Baccarani, Giovanni Martinelli
No abstract text is available yet for this article.
December 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27880933/immunological-effects-of-nilotinib-prophylaxis-after-allogeneic-stem-cell-transplantation-in-patients-with-advanced-chronic-myeloid-leukemia-or-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#8
Nira Varda-Bloom, Ivetta Danylesko, Roni Shouval, Shiran Eldror, Atar Lev, Jacqueline Davidson, Esther Rosenthal, Yulia Volchek, Noga Shem-Tov, Ronit Yerushalmi, Avichai Shimoni, Raz Somech, Arnon Nagler
Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27864817/surgical-resection-of-recurrent-gastrointestinal-stromal-tumor-after-interruption-of-long-term-nilotinib-therapy
#9
Takahito Sugase, Tsuyoshi Takahashi, Takashi Ishikawa, Hiroshi Ichikawa, Tatsuo Kanda, Seiichi Hirota, Kiyokazu Nakajima, Koji Tanaka, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Shuji Takiguchi, Toshifumi Wakai, Masaki Mori, Yuichiro Doki
BACKGROUND: Nilotinib inhibits the tyrosine kinase activities of ABL1/BCR-ABL1, KIT, and platelet-derived growth factor receptors (PDGFRs). The results of a phase III clinical trial indicated that nilotinib could not be recommended for broad use as first-line therapy for gastrointestinal stromal tumor (GIST). However, some clinical studies have reported the effectiveness of nilotinib. We report here the cases of two patients who underwent surgical resections of nilotinib-resistant lesions after long-term nilotinib administration...
December 2016: Surgical Case Reports
https://www.readbyqxmd.com/read/27861317/development-and-validation-of-a-simultaneous-quantification-method-of-fourteen-tyrosine-kinase-inhibitors-in-human-plasma-using-lc-ms-ms
#10
Huu-Hien Huynh, Claire Pressiat, Hélène Sauvageon, Isabelle Madelaine, Patricia Maslanka, Céleste Lebbé, Catherine Thieblemont, Lauriane Goldwirt, Samia Mourah
BACKGROUND: A sensitive LC-MS/MS method for the analysis in a small volume of plasma of 14 tyrosine kinase inhibitors (TKIs) currently used (imatinib, dasatinib, ibrutinib, ponatinib, trametinib, sunitinib, cobimetinib, dabrafenib, erlotinib, lapatinib, nilotinib, bosutinib, sorafenib, and vemurafenib) has been developed and validated. This multi-analyte LC-MS/MS assay is of interest for anticancer drug combination therapy. METHODS: After a simple protein precipitation of plasma samples, the chromatographic separation was performed using a UPLC system coupled with MS/MS in a positive ionization mode...
November 16, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27858461/how-could-patient-reported-outcomes-improve-patient-management-in-chronic-myeloid-leukemia
#11
Federico De Marchi, Marta Medeot, Renato Fanin, Mario Tiribelli
Patients reported outcome (PRO) are still under-used in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), though data on the correlation between quality of life (QoL) and therapeutic efficacy are increasingly known. Chronic low-grade toxicities can reduce patient's QoL and negatively impact on adherence. Areas covered: This review will focus on the role of QoL questionnaires in patients with CML, receiving imatinib or newer TKIs (dasatinib, nilotinib, bosutinib, ponatinib)...
November 30, 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27852118/risk-of-arterial-and-venous-occlusive-events-in-chronic-myeloid-leukemia-patients-treated-with-new-generation-bcr-abl-tyrosine-kinase-inhibitors-a-systematic-review-and-meta-analysis
#12
Hélène Haguet, Jonathan Douxfils, François Mullier, Christian Chatelain, Carlos Graux, Jean-Michel Dogné
BACKGROUND: A previous meta-analysis demonstrated that 3 of the new-generation BCR-ABL tyrosine kinase inhibitors (TKIs) (dasatinib, nilotinib and ponatinib) are associated with an increased risk of vascular occlusive events in patients with Ph+ chronic myeloid leukemia compared with imatinib. This meta-analysis of randomized controlled trials aims at assessing these risks separately. METHODS: The literature search was performed by two independent reviewers following the previous protocol (PROSPERO 2014:CRD42014014147)...
November 28, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27843612/tki-induced-pure-red-cell-aplasia-first-case-report-of-pure-red-cell-aplasia-with-both-imatinib-and-nilotinib
#13
Bishesh Sharma Poudyal, Sampurna Tuladhar, Bishal Gyawali
Tyrosine-kinase inhibitors (TKIs) represent the only hopes for long-term survival for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours. Thus, uninterrupted use of TKIs is of importance in such patients. Pure red cell aplasia (PRCA) is a rare disorder, not previously known to be associated with TKIs. We present, to the best of our knowledge, the first case of a patient with CML who developed PRCA secondary to both imatinib and nilotinib. Although PRCA was controlled on withdrawal of TKI, TKI continuation in the patient with CML is important...
2016: ESMO Open
https://www.readbyqxmd.com/read/27823647/proposal-for-a-tailored-stratification-at-baseline-and-monitoring-of-cardiovascular-effects-during-follow-up-in-chronic-phase-chronic-myeloid-leukemia-patients-treated-with-nilotinib-frontline
#14
REVIEW
Massimo Breccia, Eleonora Arboscello, Andrea Bellodi, Gioia Colafigli, Matteo Molica, Micaela Bergamaschi, Fulvio Massaro, Luisa Quattrocchi, Matteo Sarocchi, Paolo Spallarossa, Giuliana Alimena
Nilotinib was approved for chronic myeloid leukemia patients in chronic phase or accelerated phase after resistance to imatinib or as frontline treatment. The drug, as other tyrosine kinase inhibitor has a specific safety profile with possible occurring metabolic side effects, such as increased glycaemia and cholesterol level, that may result, in predisposed patients, in an increased rate of cardiac and vascular disorders. The objectives of this paper were to focus on the optimal procedures to perform at diagnosis in order to identify patients at risk of possible events and the correct monitoring procedures in order to prevent and manage metabolic and cardiovascular adverse events...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27821800/synergistic-effects-of-selective-inhibitors-targeting-the-pi3k-akt-mtor-pathway-or-nup214-abl1-fusion-protein-in-human-acute-lymphoblastic-leukemia
#15
Carolina Simioni, Simona Ultimo, Alberto M Martelli, Giorgio Zauli, Daniela Milani, James A McCubrey, Silvano Capitani, Luca M Neri
Philadelphia chromosome-positive (Ph+) Acute Lymphoblastic Leukemia (ALL) accounts for 25-30% of adult ALL and its incidence increases with age in adults >40 years old. Irrespective of age, the ABL1 fusion genes are markers of poor prognosis and amplification of the NUP214-ABL1 oncogene can be detected mainly in patients with T-ALL. T cell malignancies harboring the ABL1 fusion genes are sensitive to many cytotoxic agents, but up to date complete remissions have not been achieved. The PI3K/Akt/mTOR signaling pathway is often activated in leukemias and plays a crucial role in leukemogenesis...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27784336/a-proof-of-concept-study-with-the-tyrosine-kinase-inhibitor-nilotinib-in-spondyloarthritis
#16
Jacqueline E Paramarta, Maureen C Turina, Troy Noordenbos, Tanja F Heijda, Iris C Blijdorp, Nataliya Yeremenko, Dominique Baeten
BACKGROUND: To evaluate the immunomodulating and clinical effects of nilotinib, a tyrosine kinase inhibitor, in a proof-of-concept study in spondyloarthritis (SpA) assessing the mast cell as potential novel therapeutic target in this disease. METHODS: Twenty eight patients with active peripheral (pSpA) and/or axial SpA (axSpA) were included in a randomized, double-blind, placebo-controlled clinical trial (Trial registration: Trialregister.nl NTR2834). Patients were treated 1:1 with nilotinib or placebo for 12 weeks, followed by an open label extension for another 12 weeks...
October 27, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27771544/switching-to-nilotinib-in-patients-with-chronic-myeloid-leukemia-in-chronic-phase-with-molecular-suboptimal-response-to-frontline-imatinib-sensor-final-results-and-bim-polymorphism-substudy
#17
Koichi Miyamura, Toshihiro Miyamoto, Mitsune Tanimoto, Kazuhito Yamamoto, Shinya Kimura, Tatsuya Kawaguchi, Itaru Matsumura, Tomoko Hata, Hisashi Tsurumi, Shigeki Saito, Masayuki Hino, Seiji Tadokoro, Kuniaki Meguro, Hideo Hyodo, Masahide Yamamoto, Kohmei Kubo, Junichi Tsukada, Midori Kondo, Makoto Aoki, Hikaru Okada, Masamitsu Yanada, Kazuma Ohyashiki, Masafumi Taniwaki
Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months...
December 2016: Leukemia Research
https://www.readbyqxmd.com/read/27770583/a-population-based-study-of-chronic-myeloid-leukemia-patients-treated-with-imatinib-in-first-line
#18
Fausto Castagnetti, Francesco Di Raimondo, Antonio De Vivo, Antonio Spitaleri, Gabriele Gugliotta, Francesco Fabbiano, Isabella Capodanno, Donato Mannina, Marzia Salvucci, Agostino Antolino, Roberto Marasca, Maurizio Musso, Monica Crugnola, Stefana Impera, Elena Trabacchi, Caterina Musolino, Francesco Cavazzini, Giuseppe Mineo, Patrizia Tosi, Carmela Tomaselli, Michele Rizzo, Sergio Siragusa, Miriam Fogli, Riccardo Ragionieri, Alessandro Zironi, Simona Soverini, Giovanni Martinelli, Michele Cavo, Paolo Vigneri, Fabio Stagno, Gianantonio Rosti, Michele Baccarani
Chronic myeloid leukemia (CML) treatment is based on company-sponsored and academic trials testing different tyrosine kinase inhibitors (TKIs) as first-line therapy. These studies included patients selected according to many inclusion-exclusion criteria, particularly age and comorbidities, with specific treatment obligations. In daily clinical practice (real-life), inclusion-exclusion criteria do not exist and the treatment outcome does not only depend on the choice of first-line TKI, but also on second- and third-line TKIs...
October 22, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27764539/different-anti-remodeling-effect-of-nilotinib-and-fluticasone-in-a-chronic-asthma-model
#19
Hye Seon Kang, Chin Kook Rhee, Hea Yon Lee, Hyoung Kyu Yoon, Soon Seok Kwon, Sook Young Lee
Background/Aims: Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling...
October 20, 2016: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/27764087/optimized-treatment-schedules-for-chronic-myeloid-leukemia
#20
Qie He, Junfeng Zhu, David Dingli, Jasmine Foo, Kevin Zox Leder
Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib) have been developed to treat Chronic Myeloid Leukemia (CML). Despite an initial response to therapy, drug resistance remains a problem for some CML patients. Recent studies have shown that resistance mutations that preexist treatment can be detected in a substantial number of patients, and that this may be associated with eventual treatment failure. One proposed method to extend treatment efficacy is to use a combination of multiple targeted therapies...
October 2016: PLoS Computational Biology
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