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TKIs in CML

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https://www.readbyqxmd.com/read/28109974/incidences-and-outcomes-of-therapy-related-chronic-myeloid-leukemia-in-the-era-of-tyrosine-kinase-inhibitors-surveillance-of-the-cml-cooperative-study-group
#1
Noriyoshi Iriyama, Michihide Tokuhira, Tomoiku Takaku, Eriko Sato, Maho Ishikawa, Tomonori Nakazato, Kei-Ji Sugimoto, Hiroyuki Fujita, Isao Fujioka, Yoshihiro Hatta, Masahiro Kizaki, Norio Komatsu, Norio Asou, Tatsuya Kawaguchi
This study was performed to investigate the features and outcome of patients with therapy-related chronic myeloid leukemia (TR-CML) who were treated with tyrosine kinase inhibitors (TKIs). The analysis included 308 patients with CML in the chronic phase who were extracted from the CML Cooperative Study Group database. Of these patients, 11 (3.6%) were identified as having TR-CML. No differences in age, sex, white blood cell count, hemoglobin level, platelet count, or European Treatment and Outcome Study risk were observed between patients with TR-CML vs...
January 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28099274/can-any-patients-with-chronic-myeloid-leukemia-outside-of-a-clinical-trial-have-their-tyrosine-kinase-inhibitor-discontinued
#2
Michael J Mauro
PURPOSE OF REVIEW: This article critically appraises the state of treatment-free remission as a strategy for patients with chronic myeloid leukemia (CML) in deep remission after therapy with tyrosine kinase inhibitors (TKIs). RECENT FINDINGS: Approximately half of patients with CML defined fairly narrowly by trial criteria - TKI sensitive, in deep molecular remission for a defined period - can successfully maintain protective levels of response after TKI cessation...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28093990/insight-to-pharmacokinetics-of-tkis-optimizing-practical-guidelines-for-individualized-therapy
#3
Ruiqing Wang, Chaoqin Zhong, Chen Zhang, Mingqiang Hua, Daoxin Ma
Tyrosine kinase inhibitors (TKIs) are widely used drugs which have high availability in reducing the activity of BCR-ABL1 tyrosine kinase, therefore they play an indispensable role in the treatment of Chronic myeloid leukemia (CML). Imatinib, dasatinib and nilotinib have been proved to have absolute bioavailability and stable blood concentration in humans. TKIs pharmacokinetics has close relationships with the clinical response and clinical treatment of CML. We conducted a systematic PubMed search to look for studies relating to TKIs pharmacokinetics with proper inclusion/exclusion criteria...
January 16, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28090366/bosutinib-therapy-in-patients-with-chronic-myeloid-leukemia-practical-considerations-for-management-of-side-effects
#4
REVIEW
Patricia S Ault, John Rose PharmD, Lisa A Nodzon PhD, Elizabeth S Kaled
The past decade has witnessed great advances in the treatment of chronic myeloid leukemia (CML), brought about in large part by the development of BCR-ABL tyrosine kinase inhibitors (TKIs). Bosutinib joins the armamentarium of approved TKIs for the treatment of chronic phase (CP), accelerated phase (AP), and blast phase (BP) Philadelphia chromosome (Ph)-positive CML resistant to or intolerant of prior therapy. Bosutinib has an adverse-event (AE) profile distinct from that of other TKIs. Diarrhea is the predominant toxicity associated with bosutinib treatment; other commonly reported nonhematologic AEs include rash and liver enzyme elevations...
March 2016: Journal of the Advanced Practitioner in Oncology
https://www.readbyqxmd.com/read/28052354/evaluation-of-long-term-chronic-myeloid-leukemia-treatment-practices-with-tyrosine-kinase-inhibitors-in-a-national-cohort-of-veterans
#5
Eugene D Kreys, Christopher R Frei, Sarah M Villarreal, Mary J Bollinger, Xavier Jones, Jim M Koeller
STUDY OBJECTIVE: To evaluate nationwide chronic myeloid leukemia treatment practices over an extended period and across multiple lines of tyrosine kinase inhibitor (TKI) therapy with imatinib, dasatinib, and nilotinib. DESIGN: Retrospective cohort study. DATA SOURCE: Veterans Health Administration (VHA) national database. PATIENTS: A total of 2,873 VHA beneficiaries aged 18-89 years who had at least one encounter at any of the approximately 150 VHA hospitals and 800 VHA clinics, had a diagnosis code for chronic myeloid leukemia, and filled at least one prescription for imatinib, nilotinib, or dasatinib between October 1, 2001, and September 30, 2010...
January 4, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28009456/the-impact-of-socioeconomic-factors-on-treatment-choice-and-mortality-in-chronic-myeloid-leukaemia
#6
Gunnar Larfors, Fredrik Sandin, Johan Richter, Anders Själander, Leif Stenke, Mats Lambe, Martin Höglund
PURPOSE: To evaluate the influence of socioeconomic variables on treatment selection and survival of patients with chronic myeloid leukaemia (CML). METHODS: Using information available in population-based Swedish registries we evaluated indices of health, education and economy from the 980 patients in the Swedish CML register diagnosed between 2002 and 2012. Apart from internal comparisons, five age-, gender- and region-matched control subjects per patient served as control cohort...
December 23, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27999193/the-novel-anticancer-agent-jnj-26854165-is-active-in-chronic-myeloid-leukemic-cells-with-unmutated-bcr-abl-and-t315i-mutant-bcr-abl-through-promoting-proteosomal-degradation-of-bcr-abl-proteins
#7
Liangshun You, Hui Liu, Jian Huang, Wanzhuo Xie, Jueying Wei, Xiujin Ye, Wenbin Qian
Chronic myeloid leukemia (CML) is a clonal malignant disease caused by the expression of BCR/ABL. MDM2 (human homolog of the murine double minute-2) inhibitors such as Nutlin-3 have been shown to induce apoptosis in a p53-dependent manner in CML cells and sensitize cells to Imatinib. Here, we demonstrate that JNJ-26854165, an inhibitor of MDM2, inhibits proliferation and triggers cell death in a p53-independent manner in various BCR/ABL-expressing cells, which include primary leukemic cells from patients with CML blast crisis and cells expressing the Imatinib-resistant T315I BCR/ABL mutant...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27998234/factors-associated-with-tyrosine-kinase-inhibitor-initiation-and-adherence-among-medicare-beneficiaries-with-chronic-myeloid-leukemia
#8
Aaron N Winn, Nancy L Keating, Stacie B Dusetzina
Purpose There is substantial concern surrounding affordability of orally administered anticancer therapies, particularly for Medicare beneficiaries. We examined rates of initiation and adherence to tyrosine kinase inhibitors (TKIs) among Medicare beneficiaries with chronic myeloid leukemia (CML) with and without cost-sharing subsidies. We selected TKIs given their effectiveness and strong indication for use among patients diagnosed with CML. Patients and Methods Using SEER-Medicare data, we identified individuals diagnosed with CML from 2007 to 2011...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27979961/rt-qpcr-and-rt-digital-pcr-a-comparison-of-different-platforms-for-the-evaluation-of-residual-disease-in-chronic-myeloid-leukemia
#9
Mary Alikian, Alexandra S Whale, Susanna Akiki, Kim Piechocki, Celia Torrado, Thet Myint, Simon Cowen, Michael Griffiths, Alistair G Reid, Jane Apperley, Helen White, Jim F Huggett, Letizia Foroni
BACKGROUND: Tyrosine kinase inhibitors (TKIs) are the cornerstone of successful clinical management of patients with chronic myeloid leukemia (CML). Quantitative monitoring of the percentage of the BCR, RhoGEF, and GTPase activating protein-ABL proto-oncogene 1, non-receptor tyrosine kinase fusion transcript BCR-ABL1(IS) (%BCR-ABL1(IS)) by reverse transcription-quantitative PCR (RT-qPCR) is the gold standard strategy for evaluating patient response to TKIs and classification into prognostic subgroups...
December 15, 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27957861/codelivery-of-ponatinib-and-sar302503-by-active-bone-targeted-polymeric-micelles-for-the-treatment-of-therapy-resistant-chronic-myeloid-leukemia
#10
Chao-Feng Mu, Yang Xiong, Xue Bai, Yun-Jie Sheng, Jiajun Cui
Point mutations in the BCR-ABL1 domain and primitive chronic myelogenous leukemia (CML) cells existing in the bone marrow environment insensitive to tyrosine kinase inhibitors (TKIs) have become two major challenges in the CML therapy. In this study, combined TKI ponatinib and JAK2 inhibitor SAR302503 short-term treatment effectively suppressed growth and promoted apoptosis of BaF3/T315I cells in cytokine-containing medium in vitro. SAR302503 prevented cytokine-dependent resistance to ponatinib via inhibition of JAK2/STAT5 phosphorylation...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27931141/modulation-of-leukotriene-signaling-inhibiting-cell-growth-in-chronic-myeloid-leukemia
#11
Elham Yektaei-Karin, Ana Zovko, Anders Nilsson, Barbro Näsman-Glaser, Lena Kanter, Olof Rådmark, Jonas Wallvik, Marja Ekblom, Monika Dolinska, Hong Qian, Leif Stenke
Although tyrosine kinase inhibitors (TKIs) have dramatically improved clinical outcome in chronic myeloid leukemia (CML), cure rarely occurs. This may be due to BCR-ABL-independent, aberrant signaling pathways, one of which leads to leukotriene (LT) formation. Well-recognized as inflammatory mediators, LT can also affect oncogenic mechanisms of several tumors. We have previously discovered elevated LT-synthesis and up-regulated cysteinyl-LT-inducing enzyme in CML. Here we report on dose-dependent inhibition of CML cell growth exerted by specific blockers of LT-signaling...
December 8, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27924071/the-combination-therapy-of-imatinib-and-dasatinib-achieves-long-term-molecular-response-in-two-imatinib-resistant-and-dasatinibintolerant-patients-with-advanced-chronic-myeloid-leukemia
#12
Yu Zhu, Liangqin Pan, Ming Hong, Weixing Liu, Chun Qiao, Jianyong Li, Sixuan Qian
For patients with chronic myeloid leukemia (CML) failing imatinib therapy, second-generation tyrosine kinase inhibitors (TKIs) are recommended. Here, we describe two patients with advanced CML who failed imatinib therapy and did not tolerate the recommended dose of dasatinib, but then achieved a major molecular response with the combination of imatinib and dasatinib with no significant extramedullary toxicity. Our observations suggest that combination of TKIs may provide an additive/synergistic antileukemic effect...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27919989/teratogenic-effect-of-radotinib-case-report
#13
Juyoung Cheon, Jung Whan Ahn, Kyung Min Park, Guisera Lee, Yun Sung Jo
BACKGROUND: Simultaneous presentation of pregnancy and chronic myeloid leukemia (CML) is rare. Tyrosine kinase inhibitors (TKIs) are rarely used in pregnancy. There is almost no information on the effect of recently developed TKIs on the fetus. CASE REPORT: A 22-year-old woman became pregnant while using radotinib, a novel TKI for CML. She was concerned about the possible teratogenic effect of radotinib; hence the first pregnancy was terminated. The patient underwent full-term delivery at the second pregnancy...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27913477/the-value-of-quality-of-life-assessment-in-chronic-myeloid-leukemia-patients-receiving-tyrosine-kinase-inhibitors
#14
Fabio Efficace, Laura Cannella
The development of the oral tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML) is one of the great triumphs of cancer research. Although the efficacy of TKIs has dramatically improved the disease-specific overall survival rate, the prevalence of CML is increasing worldwide. Currently, CML patients receive prolonged (even lifelong) treatment, and over the last decade, clinical decision making has become challenging. Therefore, consideration of the effects of TKI therapies on patients' quality of life (QoL) and symptom burden (ie, patient-reported outcomes [PROs]) is now critical to more robustly inform patient care and improve health care quality...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913475/molecular-monitoring-in-chronic-myeloid-leukemia-how-low-can-you-go
#15
Susan Branford
Molecular monitoring of BCR-ABL1 transcripts for patients with chronic myeloid leukemia (CML) is now used to assess response to tyrosine kinase inhibitors (TKIs), including treatment failure that mandates a change of therapy. Therefore, many centers have adopted the molecular technique for measuring BCR-ABL1 and rely on conversion of values to the international reporting scale for appropriate clinical interpretation. However, the technique has a degree of inherent variability despite standardized procedures, which means care should be taken by the clinician when assessing response based on BCR-ABL1 cutoff limits...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27904889/reactive-oxygen-species-in-bcr-abl1-expressing-cells-relevance-to-chronic-myeloid-leukemia
#16
Joanna Antoszewska-Smith, Elzbieta Pawlowska, Janusz Blasiak
Chronic myeloid leukemia (CML) results from the t(9;22) reciprocal chromosomal translocation producing the BCR-ABL1 gene, conferring growth and proliferation advantages in the CML cells. CML progresses from chronic, often syndrome-free, to blast phase, fatal if not treated. Although the involvement of BCR-ABL1 in some signaling pathways is considered as the cause of CML, the mechanisms resulting in its progression are not completely known. However, BCR-ABL1 stimulates the production of reactive oxygen species (ROS), which levels increase with CML progression and induce BCR-ABL1 self-mutagenesis...
December 1, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27901368/second-line-small-molecule-therapy-options-for-treating-chronic-myeloid-leukemia
#17
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...
January 2017: Expert Opinion on Pharmacotherapy
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
#18
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/27858461/how-could-patient-reported-outcomes-improve-patient-management-in-chronic-myeloid-leukemia
#19
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)...
January 2017: Expert Review of Hematology
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
#20
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
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