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TKIs in CML

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https://www.readbyqxmd.com/read/28209750/stopping-second-generation-tkis-in-cml
#1
Pierre Laneuville
No abstract text is available yet for this article.
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28194061/performance-of-sokal-and-eutos-scores-for-predicting-cytogenetic-and-molecular-response-in-newly-diagnosed-chronic-myeloid-leukemia-chronic-phase-patients-on-imatinib
#2
Sandip Ganguly, K C Lakshmaiah, Linu Abraham Jacob, Suresh Babu, Lokanatha Dasappa, K S Govind Babu
Sokal index was developed in the pre-imatinib era to predict and prognosticate the outcome of Chronic myeloid leukemia (CML) patients. In the Imatinib era, a new scoring system called EUTOS scoring system has been validated as a predictive marker in CML. The scores have shown variable correlation with complete cytogenetic response (CCyR) and major molecular response (MMR). To assess the performance of Sokal score and EUTOS score as a predictive marker for CCyR and MMR for newly diagnosed CML-CP patients treated with TKIs...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28186983/differentiation-status-of-primary-chronic-myeloid-leukemia-cells-affects-sensitivity-to-bcr-abl1-inhibitors
#3
Paavo O Pietarinen, Christopher A Eide, Pilar Ayuda-Durán, Swapnil Potdar, Heikki Kuusanmäki, Emma I Andersson, John P Mpindi, Tea Pemovska, Mika Kontro, Caroline A Heckman, Olli Kallioniemi, Krister Wennerberg, Henrik Hjorth-Hansen, Brian J Druker, Jorrit M Enserink, Jeffrey W Tyner, Satu Mustjoki, Kimmo Porkka
Tyrosine kinase inhibitors (TKI) are the mainstay treatment of BCR-ABL1-positive leukemia and virtually all patients with chronic myeloid leukemia in chronic phase (CP CML) respond to TKI therapy. However, there is limited information on the cellular mechanisms of response and particularly on the effect of cell differentiation state to TKI sensitivity in vivo and ex vivo/in vitro. We used multiple, independent high-throughput drug sensitivity and resistance testing platforms that collectively evaluated 295 oncology compounds to characterize ex vivo drug response profiles of primary cells freshly collected from newly-diagnosed patients with BCR-ABL1-positive leukemia (n = 40) and healthy controls (n = 12)...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159740/the-chronic-myeloid-leukemia-stem-cell-stemming-the-tide-of-persistence
#4
Tessa L Holyoake, David Vetrie
Chronic myeloid leukaemia (CML) is caused by the acquisition of the tyrosine kinase BCR-ABL1 in a haemopoietic stem cell (HSC), transforming it into a leukaemic stem cell (LSC) that self-renews, proliferates and differentiates to give rise to a myeloproliferative disease. While tyrosine kinase inhibitors (TKI) that target the kinase activity of BCR-ABL1 have transformed CML from a once fatal disease to a manageable one for the vast majority of patients, only ~10% of those who present in chronic phase (CP) can discontinue TKI treatment and maintain a therapy-free remission...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28135648/current-approach-to-the-treatment-of-chronic-myeloid-leukaemia
#5
REVIEW
Ivan Pasic, Jeffrey H Lipton
Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28125373/health-care-resource-utilization-and-costs-in-patients-with-chronic-myeloid-leukemia-with-better-adherence-to-tyrosine-kinase-inhibitors-and-increased-molecular-monitoring-frequency
#6
Dominick Latremouille-Viau, Annie Guerin, Patrick Gagnon-Sanschagrin, Katherine Dea, Benjamin G Cohen, George J Joseph
BACKGROUND: Frequent molecular monitoring (qPCR tests), as recommended by evidence-based monitoring guidelines, is associated with higher adherence to tyrosine kinase inhibitors (TKIs) in the management of chronic myeloid leukemia (CML); both factors have been associated with better clinical and economic outcomes. OBJECTIVES: To (a) estimate the effect of more frequent qPCR tests on health care resource utilization (HRU) and associated costs, including direct (effect of qPCR test frequency on HRU) and indirect (through TKI adherence) effects, and (b) develop an economic model applicable to multiple clinical practice scenarios...
February 2017: Journal of Managed Care & Specialty Pharmacy
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
#7
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
#8
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...
March 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28093990/insight-to-pharmacokinetics-of-tkis-optimizing-practical-guidelines-for-individualized-therapy
#9
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
#10
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
#11
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
#12
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
#13
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...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27998234/factors-associated-with-tyrosine-kinase-inhibitor-initiation-and-adherence-among-medicare-beneficiaries-with-chronic-myeloid-leukemia
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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