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TKIs in CML

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https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#1
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28801986/persistent-detection-of-alternatively-spliced-bcr-abl-variant-results-in-a-failure-to-achieve-deep-molecular-response
#2
Junichiro Yuda, Toshihiro Miyamoto, Jun Odawara, Yasuyuki Ohkawa, Yuichiro Semba, Masayasu Hayashi, Koichi Miyamura, Mitsune Tanimoto, Kazuhito Yamamoto, Masafumi Taniwaki, Koichi Akashi
Treatment with tyrosine kinase inhibitors (TKIs) may sequentially induce TKI-resistant BCR-ABL mutants in chronic myeloid leukemia (CML). Conventional polymerase chain reaction (PCR) monitoring of BCR-ABL is an important indicator to determine therapeutic intervention for preventing disease progression. However, PCR cannot quantify separately amounts of BCR-ABL and its mutants, including alternatively spliced BCR-ABL with an insertion of 35 intronic nucleotides (BCR-ABL(I)(ns35bp) ) between ABL exons 8 and 9 which introduces the premature termination and loss of kinase activity...
August 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28774214/the-safety-of-bosutinib-for-the-treatment-of-chronic-myeloid-leukemia
#3
Jee Hyun Kong, H J Khoury, Audrey Sunwha Kim, Brittany Gray Hill, Vamsi Kota
Introduction Tyrosine kinase inhibitors (TKIs) are a potentially lifelong treatment for patients with chronic myeloid leukemia (CML). Adverse events (AEs) associated with TKIs are significant impediments in the daily life of patients that can impact compliance, and efficacy. Areas covered This is a review on safety of bosutinib in the treatment of chronic phase CML. Data is extracted from the latest updates of bosutinib phase I/II and III trials. Expert opinion Bosutinib is an effective agent against all phases of CML presently approved for the treatment in patients with resistance or intolerance to prior TKI therapy...
August 3, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28772207/bone-marrow-mesenchymal-stromal-cell-msc-gene-profiling-in-chronic-myeloid-leukemia-cml-patients-at-diagnosis-and-in-deep-molecular-response-induced-by-tyrosine-kinase-inhibitors-tkis
#4
Djamel Aggoune, Nathalie Sorel, Marie-Laure Bonnet, Jean-Michel Goujon, Karin Tarte, Olivier Hérault, Jorge Domenech, Delphine Réa, Laurence Legros, Hyacinthe Johnson-Ansa, Philippe Rousselot, Emilie Cayssials, Agnès Guerci-Bresler, Annelise Bennaceur-Griscelli, Jean-Claude Chomel, Ali G Turhan
Although it has been well-demonstrated that bone marrow mesenchymal stromal cells (MSCs) from CML patients do not belong to the Ph1-positive clone, there is growing evidence that they could play a role in the leukemogenesis process or the protection of leukemic stem cells from the effects of tyrosine kinase inhibitors (TKIs). The aim of the present study was to identify genes differentially expressed in MSCs isolated from CML patients at diagnosis (CML-MSCs) as compared to MSCs from healthy controls. Using a custom gene-profiling assay, we identified six genes over-expressed in CML-MSCs (BMP1, FOXO3, MET, MITF, NANOG, PDPN), with the two highest levels being documented for PDPN (PODOPLANIN) and NANOG...
July 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28760296/analysis-of-survival-of-patients-with-chronic-myeloid-leukemia-treated-with-imatinib-in-the-last-15-years-in-lebanon
#5
Marcel Massoud, Riwa Sakr, Fouad Kerbage, Joseph Makdissi, Jenny Hawi, Layale Rached, Fady Nasr, Georges Chahine
BACKGROUND: In the 2000s, the introduction of the tyrosine kinase inhibitor (TKI), imatinib, improved the survival outcomes of patients with chronic myeloid leukemia (CML). In Lebanon, we rapidly adopted this treatment strategy. To the best of our knowledge, this is the first study reporting the survival rates of Lebanese CML patients. We examined the rates of major molecular response (MMR) and complete cytogenetic response (CCyR) and analyzed the overall survival, progression-free survival, and event-free survival of CML patients treated with front-line imatinib in 3 university hospitals in Lebanon...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28756878/heme-oxygenase-1-a-new-druggable-target-in-the-management-of-chronic-and-acute-myeloid-leukemia
#6
REVIEW
Loredana Salerno, Giuseppe Romeo, Maria N Modica, Emanuele Amata, Valeria Sorrenti, Ignazio Barbagallo, Valeria Pittalà
Heme oxygenase-1 (HO-1) is the enzyme catalyzing the rate-limiting oxidative degradation of cellular heme into free iron, carbon monoxide (CO), and biliverdin, which is then rapidly converted into bilirubin. By means of these catabolic end-products and by removal of pro-oxidant heme, HO-1 exerts antioxidant, antiapoptotic, and immune-modulating effects, leading to overall cytoprotective and beneficial functions in mammalian cells. Therefore, HO-1 is considered a survival molecule in various stress-related conditions...
July 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28752827/clinical-pathway-for-patients-with-chronic-myeloid-leukaemia-the-euriclea-project
#7
Stefano Botti, Gianpaolo Gargiulo, Felice Bombaci, Giovanna Artioli, Chiara Cosentino, Adriana Concetta Pignatelli, Daniela Torino, Maria Marcella Lionetti, Emanuela Samarani, Lorella Cappucciati, Paola Bordiga, Antonella Diodati, Cristiana Caffarri, Irene Rosini, Fabrizio Pane
BACKGROUND AND AIMS: The use of Tirosine Kinase Ihnibitors (TKIs) for the treatment of Chronic Myeloid Leukemia (CML) has definitely represented a turning point in the treatment of the onco-hematological diseases. Over the years, the interest of physicians, nurses, patients and caregivers has increasingly focused on the aspects of the humanization of care, the management of side effects and on the full and constant therapeutic adherence. The aim of the project was to define patient-oriented care processes, based on a proactive approach that can fully respond to the new health needs of CML patients...
July 18, 2017: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/28749622/understanding-and-challenges-in-taking-tyrosine-kinase-inhibitors-among-malaysian-chronic-myeloid-leukemia-patients-a-qualitative-study
#8
Yik Ming Lim, Wei Lerk Eng, Huan Keat Chan
Background: In Malaysia, the treatment for chronic myeloid leukemia (CML) has long been delivered under the Malaysian Patient Assistance Program (MYPAP), but research on identifying factors contributing to non-adherence to tyrosine kinase inhibitors (TKIs) is still limited. The current study explored understanding and challenges of Malaysian CML patients in taking imatinib and nilotinib. Methods: Semi-structured, face-to-face interviews were conducted with 13 CML patients receiving treatment at a public tertiary care center, and were analyzed using the content analysis approach...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28743166/second-tyrosine-kinase-inhibitor-discontinuation-attempt-in-patients-with-chronic-myeloid-leukemia
#9
Laurence Legros, Franck E Nicolini, Gabriel Etienne, Philippe Rousselot, Delphine Rea, Stéphane Giraudier, Agnès Guerci-Bresler, Françoise Huguet, Martine Gardembas, Martine Escoffre, Jean-Christophe Ianotto, Marie-Pierre Noël, Bruno R Varet, Thomas Pagliardini, Irit Touitou, Stéphane Morisset, Francois-Xavier Mahon
BACKGROUND: Several studies have demonstrated that approximately one-half of patients with chronic myeloid leukemia (CML) who receive treatment with tyrosine kinase inhibitors (TKIs) and achieve and maintain a deep molecular response (DMR) are able to successfully discontinue therapy. In patients who have a molecular relapse, a DMR is rapidly regained upon treatment re-initiation. METHODS: The authors report the results from RE-STIM, a French observational, multicenter study that evaluated treatment-free remission (TFR) in 70 patients who re-attempted TKI discontinuation after a first unsuccessful attempt...
July 25, 2017: Cancer
https://www.readbyqxmd.com/read/28742419/insights-into-the-management-of-chronic-myeloid-leukemia-in-resource-poor-settings-a-mexican-perspective
#10
Andrés Gomez-de-León, David Gómez-Almaguer, Guillermo J Ruiz-Delgado, Guillermo J Ruiz-Arguelles
The arrival of targeted therapy for chronic myeloid leukemia (CML) was revolutionary. However, due to the high cost of tyrosine kinase inhibitors, access to this highly effective therapy with strict monitoring strategies is limited in low to middle-income countries. In this context, following standard recommendations proposed by experts in developed countries is difficult. Areas covered: This review aims to provide an insight into the management of patients with CML living in a resource-limited setting. It addresses several issues: diagnosis, initial treatment, disease monitoring, and additional treatment alternatives including allogeneic hematopoietic stem cell transplantation...
August 3, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28719608/cholesterol-esterification-inhibition-and-imatinib-treatment-synergistically-inhibit-growth-of-bcr-abl-mutation-independent-resistant-chronic-myelogenous-leukemia
#11
Shovik Bandyopadhyay, Junjie Li, Elie Traer, Jeffrey W Tyner, Amy Zhou, Stephen T Oh, Ji-Xin Cheng
Since the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib, chronic myelogenous leukemia (CML) prognosis has improved greatly. However, ~30-40% of patients develop resistance to imatinib therapy. Although most resistance is caused by mutations in the BCR-ABL kinase domain, 50-85% of these patients develop resistance in the absence of new mutations. In these cases, targeting other pathways may be needed to regain clinical response. Using label-free Raman spectromicroscopy, we evaluated a number of leukemia cell lines and discovered an aberrant accumulation of cholesteryl ester (CE) in CML, which was found to be a result of BCR-ABL kinase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28715941/moderate-anemia-at-diagnosis-is-an-independent-prognostic-marker-of-the-eutos-sokal-and-hasford-scores-for-survival-and-treatment-response-in-chronic-phase-chronic-myeloid-leukemia-patients-with-frontline-imatinib
#12
Po-Shen Ko, Yuan-Bin Yu, Yao-Chung Liu, Yi-Tsui Wu, Man-Hsin Hung, Jyh-Pyng Gau, Chia-Jen Liu, Liang-Tsai Hsiao, Po-Min Chen, Tzeon-Jye Chiou, Chun-Yu Liu, Jin-Hwang Liu
OBJECTIVES: We aimed to examine the prognostic value of anemia for the diagnosis of chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib. METHODS: One hundred fifty-four CML-CP patients were enrolled. The influences of moderate anemia with hemoglobin (Hb) < 10 g/dl, four scoring systems and the early molecular response at three months (BCR-ABL ≤ 10%; 3M-EMR) on the achievement of a deep molecular response (DMR, MR4.5), progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) were compared...
July 18, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28706179/nilotinib-induced-recurrent-gastric-polyps-case-report-and-review-of-literature
#13
Nancy Kassem, Omar M Ismail, Halima Elomri, Mohamad A Yassin
BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment...
July 14, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28667884/exome-sequencing-reveals-dnmt3a-and-asxl1-variants-associate-with-progression-of-chronic-myeloid-leukemia-after-tyrosine-kinase-inhibitor-therapy
#14
TaeHyung Kim, Marc S Tyndel, Zhaolei Zhang, Jaesook Ahn, Seunghyun Choi, Michael Szardenings, Jeffrey H Lipton, Hyeoung-Joon Kim, Dennis Kim Dong Hwan
OBJECTIVE: The development of tyrosine kinase inhibitors (TKIs) has significantly improved the treatment of chronic myeloid leukemia (CML). However, approximately one third of patients are resistant to TKI and/or progress to advanced disease stages. TKI therapy failure has a well-known association with ABL1 kinase domain (KD) mutations, but only around half of TKI non-responders have detectable ABL1 KD mutations. METHOD: We attempt to identify genetic markers associated with TKI therapy failure in 13 patients (5 resistant, 8 progressed) without ABL1 KD mutations using whole-exome sequencing...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28652712/medication-related-issues-associated-with-adherence-to-long-term-tyrosine-kinase-inhibitors-for-controlling-chronic-myeloid-leukemia-a-qualitative-study
#15
Bee Kim Tan, Seng Beng Tan, Li-Chia Chen, Kian Meng Chang, Siew Siang Chua, Sharmini Balashanker, Habiba Nazeera Begum Kamarul Jaman, Syed Carlo Edmund, Ping Chong Bee
PURPOSE: Poor adherence to tyrosine kinase inhibitors (TKIs) could compromise the control of chronic myeloid leukemia (CML) and contributes to poorer survival. Little is known about how medication-related issues affect CML patients' adherence to TKI therapy in Malaysia. This qualitative study aimed to explore these issues. PATIENTS AND METHODS: Individual face-to-face, semistructured interviews were conducted at the hematology outpatient clinics of two medical centers in Malaysia from August 2015 to January 2016...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28617066/patient-perceptions-of-treatment-free-remission-in-chronic-myeloid-leukemia
#16
Lucia A Villemagne Sanchez, Clare O'Callaghan, Karla Gough, Karen Hall, Yoshihisa Kashima, John F Seymour, Penelope Schofield, David M Ross
Around half of patients with chronic myeloid leukemia (CML) who achieve a stable deep molecular response would remain in treatment-free remission (TFR) if their tyrosine kinase inhibitors (TKIs) were stopped. TFR is increasingly becoming a goal of treatment. Eighty-seven patients answered a survey exploring patient perceptions of TFR, incorporating CML-specific factors (disease history, treatment toxicity, and adherence) and questions concerning health beliefs. 81% of participants (95% CI: 72%-89%) indicated that they would be willing to attempt TFR...
June 15, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28599273/targeting-bcr-abl-stem-progenitor-cells-and-bcr-abl-t315i-mutant-cells-by-effective-inhibition-of-the-bcr-abl-tyr177-grb2-complex
#17
Min Chen, Ali G Turhan, Hongxia Ding, Qingcong Lin, Kun Meng, Xiaoyan Jiang
Treatment of BCR-ABL+ human leukemia has been significantly improved by ABL tyrosine kinase inhibitors (TKIs), but they are not curative for most patients and relapses are frequently associated with BCR-ABL mutations, warranting new targets for improved treatments. We have now demonstrated that protein expression of human estrogen receptor alpha 36 (ERα36), an alternative splicing variant of human estrogen receptor alpha 66 (ERα66), is highly increased in TKI-insensitive CD34+ chronic myeloid leukemia (CML) cells and BCR-ABL-T315I mutant cells, and is abnormally localized in plasma membrane and cytoplasm...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28583043/intracranial-stenting-for-nilotinib-treatment-associated-cerebrovascular-stenosis-in-chronic-myeloid-leukemia
#18
Tomohiko Ozaki, Hajime Nakamura, Nobuyuki Izutsu, Hiroaki Masaie, Jun Ishikawa, Manabu Kinoshita
One of the second-generation tyrosine kinase inhibitors (TKIs), nilotinib, is increasingly used for imatinib-resistant or intolerant chronic myeloid leukemia (CML). Nilotinib is considered well tolerated with few side effects including hyperglycemia, hyperbilirubinemia and elevated levels of pancreatic enzymes. However, there is growing evidence that nilotinib accelerates atherosclerosis and causes peripheral arterial occlusive disease such as stroke, transient ischemic attack (TIA) and cardiovascular diseases...
January 1, 2017: Interventional Neuroradiology
https://www.readbyqxmd.com/read/28561719/chronic-myeloid-leukemia-what-every-practitioner-needs-to-know-in-2017
#19
Hanna Jean Khoury, Loretta A Williams, Ehab Atallah, Rüdiger Hehlmann
The prognosis of chronic phase chronic myeloid leukemia (CML) has improved so that life expectancy for patients responding to tyrosine kinase inhibitors (TKIs) is now equivalent to age-matched controls. Attention should be paid to comorbidities that impact survival. The success of TKI therapy can be easily and reliably assessed at well-accepted time points using quantitative polymerase chain reaction (PCR) standardized to the international scale. Patient-reported outcome (PRO) tools are readily available for use in the clinic and provide complementary information on the tolerance of TKIs...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28543934/clinical-impact-of-pretransplant-use-of-multiple-tyrosine-kinase-inhibitors-on-the-outcome-of-allogeneic-hematopoietic-stem-cell-transplantation-for-chronic-myelogenous-leukemia
#20
MULTICENTER STUDY
Takeshi Kondo, Tokiko Nagamura-Inoue, Arinobu Tojo, Fumitaka Nagamura, Naoyuki Uchida, Hirohisa Nakamae, Takahiro Fukuda, Takehiko Mori, Shingo Yano, Mineo Kurokawa, Hironori Ueno, Heiwa Kanamori, Hisako Hashimoto, Makoto Onizuka, Minoko Takanashi, Tatsuo Ichinohe, Yoshiko Atsuta, Kazuteru Ohashi
Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with chronic myelogenous leukemia in the chronic phase (CML-CP), and outcomes of TKI treatment for patients with CML-CP have been excellent. Since multiple TKIs are currently available, second-line or third-line TKI therapy is considered for patients who are intolerant of or resistant to the previous TKI treatment. Therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered only for patients with disease progression or for patients after treatment failure with multiple TKIs...
September 2017: American Journal of Hematology
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