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TKI CML

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https://www.readbyqxmd.com/read/28743166/second-tyrosine-kinase-inhibitor-discontinuation-attempt-in-patients-with-chronic-myeloid-leukemia
#1
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/28743165/prognostic-factors-and-survival-outcomes-in-patients-with-chronic-myeloid-leukemia-in-blast-phase-in-the-tyrosine-kinase-inhibitor-era-cohort-study-of-477-patients
#2
Preetesh Jain, Hagop M Kantarjian, Ahmad Ghorab, Koji Sasaki, Elias J Jabbour, Graciela Nogueras Gonzalez, Rashmi Kanagal-Shamanna, Ghayas C Issa, Guillermo Garcia-Manero, Devendra Kc, Sara Dellasala, Sherry Pierce, Marina Konopleva, William G Wierda, Srdan Verstovsek, Naval G Daver, Tapan M Kadia, Gautam Borthakur, Susan O'Brien, Zeev Estrov, Farhad Ravandi, Jorge E Cortes
BACKGROUND: Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era. METHODS: A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival...
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
#3
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...
July 25, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28721056/onset-of-chronic-myeloid-leukemia-with-complex-karyotype-in-a-pregnant-patient-case-report-and-revision-of-literature
#4
Nicola Sgherza, Elisabetta Abruzzese, Gianni Perla, Maria Marta Minervini, Vincenzo Chiello, Natale Sciannamè, Nicola Cascavilla
Approximately 10%-12% of patients in chronic-phase chronic myeloid leukemia (CP-CML) have additional chromosomal aberrations at diagnosis; moreover, CML occurs in up to 10% of pregnancy-associated leukemias, with an annual incidence of 1 per 100,000 pregnancies. In this report we describe the case of a 36-year-old female with CP-CML diagnosed in the 18th week of pregnancy and with a new complex variant translocation t(4;9;22;21)(q24;q34;q11;q22) and an additional chromosomal aberration t(1;20)(p36;p11). In consideration of her pregnancy, the patient strictly monitored her blood cell count without any specific treatment...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28719608/cholesterol-esterification-inhibition-and-imatinib-treatment-synergistically-inhibit-growth-of-bcr-abl-mutation-independent-resistant-chronic-myelogenous-leukemia
#5
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/28706179/nilotinib-induced-recurrent-gastric-polyps-case-report-and-review-of-literature
#6
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/28689264/treatment-free-remission-in-patients-with-chronic-myeloid-leukemia
#7
REVIEW
Delphine Rea, Jean-Michel Cayuela
Clinical trials have formally demonstrated that in chronic myeloid leukemia (CML), patients treated with tyrosine kinase inhibitors (TKI) who achieved and maintained deep molecular responses could discontinue their treatment after several years without facing overt signs of disease relapse in approximately 50% of the cases. In patients with a molecular relapse, prompt re-introduction of TKI therapy was able to rapidly restore deep molecular responses. The concept of a lifelong therapy with TKI has thus been challenged and treatment-free remission (TFR) strategies will soon integrate clinical practice, providing that safe recommendations will be established...
July 8, 2017: International Journal of Hematology
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
#8
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
#9
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/28637510/a-new-monoclonal-antibody-detects-downregulation-of-protein-tyrosine-phosphatase-receptor-type-%C3%AE-in-chronic-myeloid-leukemia-patients
#10
Marzia Vezzalini, Andrea Mafficini, Luisa Tomasello, Erika Lorenzetto, Elisabetta Moratti, Zeno Fiorini, Tessa L Holyoake, Francesca Pellicano, Mauro Krampera, Cristina Tecchio, Mohamed Yassin, Nader Al-Dewik, Mohamed A Ismail, Ali Al Sayab, Maria Monne, Claudio Sorio
BACKGROUND: Protein tyrosine phosphatase receptor gamma (PTPRG) is a ubiquitously expressed member of the protein tyrosine phosphatase family known to act as a tumor suppressor gene in many different neoplasms with mechanisms of inactivation including mutations and methylation of CpG islands in the promoter region. Although a critical role in human hematopoiesis and an oncosuppressor role in chronic myeloid leukemia (CML) have been reported, only one polyclonal antibody (named chPTPRG) has been described as capable of recognizing the native antigen of this phosphatase by flow cytometry...
June 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28636094/characterization-of-clonal-philadelphia-negative-cytogenetic-abnormalities-in-a-large-cohort-of-chronic-myeloid-leukemia
#11
Xiangjun Chen, Jine Zheng, Kaiwei Liang, Yanli He, Wen Du, Juan Li, Wei Liu, Yanjie Hu, Junxia Yao
OBJECTIVES: Clonal Philadelphia-negative Cytogenetic Abnormalities (CPCA) have been reported in chronic myeloid leukaemia (CML) patients treated with either interferon or tyrosine kinase inhibitor (TKI). However, the incidences and types of these cytogenetic abnormalities after treatment vary due to the limited populations enrolled. METHODS: We analysed the frequency and types of CPCA in a cohort of 607 CML patients in the chronic phase after TKI treatment. We also followed up these CPCA with a median of 31...
June 21, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28617066/patient-perceptions-of-treatment-free-remission-in-chronic-myeloid-leukemia
#12
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
#13
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/28596647/audio-vestibular-status-in-cml-patients-on-imatinib-mesylate-with-review-of-literature
#14
Rijuneeta Gupta, Uday Yanamandra, Bhumika Gupta, Naresh K Panda, Subhash Varma, Anu Nagarkar, Pankaj Malhotra
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm occasionally presenting with features of leukostasis as primary symptoms. Hearing loss is occasionally reported in CML patients. Further whether Imatinib mesylate has any effect on vestibular functions is not known. We conducted a preliminary study to assess hearing pattern in patients with CML on long term TKI therapy. This is a single center, cross sectional study from northern-India. Patients of CML who were on regular Tyrosine kinase inhibitors (TKI) therapy for at least 6 months underwent audiovestibular evaluation ...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28576876/targeting-chronic-myeloid-leukemia-stem-cells-with-the-hypoxia-inducible-factor-inhibitor-acriflavine
#15
Giulia Cheloni, Michele Tanturli, Ignazia Tusa, Ngoc Ho DeSouza, Yi Shan, Antonella Gozzini, Fréderic Mazurier, Elisabetta Rovida, Shaoguang Li, Persio Dello Sbarba
Chronic myeloid leukemia (CML) is a hematopoietic stem cell (HSC)-driven neoplasia characterized by the expression of the constitutively-active tyrosine kinase BCR/Abl. CML therapy based on tyrosine kinase inhibitors (TKi) is highly effective in inducing remission but not in targeting leukemia stem cells (LSC), which sustain minimal residual disease and are responsible for CML relapse following discontinuation of treatment. The identification of molecules capable to target LSC appears therefore of primary importance to aim at CML eradication...
June 2, 2017: Blood
https://www.readbyqxmd.com/read/28561719/chronic-myeloid-leukemia-what-every-practitioner-needs-to-know-in-2017
#16
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/28557248/ponatinib-induced-widespread-ichthyosiform-eruption
#17
F Derlino, S Barruscotti, P Zappasodi, V Brazzelli, C Vassallo
Ponatinib is a new potent third-generation tyrosine kinase inhibitor (TKI), developed for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukaemia (ALL) resistant to first (imatinib) and second generation (dasatinib and nilotinib) TK-inhibitors. Aimed at wild type and mutant BCR-ABL, ponatinib demonstrates significant anti-leukemic activity and holds much promise in treating other malignancies, including gastrointestinal stromal tumors (GIST)(1;2). This article is protected by copyright...
May 30, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28550414/dasatinib-rapidly-induces-deep-molecular-response-in-chronic-phase-chronic-myeloid-leukemia-patients-who-achieved-major-molecular-response-with-detectable-levels-of-bcr-abl1-transcripts-by-imatinib-therapy
#18
Masayuki Shiseki, Chikashi Yoshida, Naoki Takezako, Akira Ohwada, Takashi Kumagai, Kaichi Nishiwaki, Akira Horikoshi, Tetsuya Fukuda, Hina Takano, Yasuji Kouzai, Junji Tanaka, Satoshi Morita, Junichi Sakamoto, Hisashi Sakamaki, Koiti Inokuchi
BACKGROUND: With the introduction of imatinib, a first-generation tyrosine kinase inhibitor (TKI) to inhibit BCR-ABL1 kinase, the outcome of chronic-phase chronic myeloid leukemia (CP-CML) has improved dramatically. However, only a small proportion of CP-CML patients subsequently achieve a deep molecular response (DMR) with imatinib. Dasatinib, a second-generation TKI, is more potent than imatinib in the inhibition of BCR-ABL1 tyrosine kinase in vitro and more effective in CP-CML patients who do not achieve an optimal response with imatinib treatment...
May 26, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28549238/risk-factors-and-mechanisms-contributing-to-tki-induced-vascular-events-in-patients-with-cml
#19
REVIEW
Peter Valent, Emir Hadzijusufovic, Gregor Hoermann, Wolfgang Füreder, Gerit-Holger Schernthaner, Wolfgang R Sperr, Rudolf Kirchmair, Dominik Wolf
Vascular adverse events (VAE) are an emerging problem in patients with chronic myeloid leukemia (CML) receiving second-generation BCR-ABL1 tyrosine kinase inhibitors (TKI). Relevant VAE comprise peripheral, cerebral, and coronary artery changes in patients receiving nilotinib, venous and arterial occlusive events during ponatinib therapy, and pulmonary hypertension in patients receiving dasatinib. Although each TKI binds to a unique profile of molecular targets in leukemic cells and vascular cells, the exact etiology of drug-induced vasculopathies remains uncertain...
May 12, 2017: Leukemia Research
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
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...
May 20, 2017: American Journal of Hematology
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