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TKIs in CML

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https://www.readbyqxmd.com/read/28340283/comparative-analysis-of-pulmonary-hypertension-in-patients-treated-with-imatinib-nilotinib-and-dasatinib
#1
Mariko Minami, Takeshi Arita, Hiromi Iwasaki, Tsuyoshi Muta, Takatoshi Aoki, Kenichi Aoki, Satoshi Yamasaki, Takamitsu Matsushima, Koji Kato, Katsuto Takenaka, Kazuki Tanimoto, Tomohiko Kamimura, Ryosuke Ogawa, Koichi Akashi, Toshihiro Miyamoto
Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28319280/nilotinib-induced-panniculitis-in-a-patient-with-chronic-myelogenous-leukemia
#2
Naomi Kitayama, Atsushi Otsuka, Chiaki Hamamoto, Yo Kaku, Hiroshi Shiragami, Yoshiyuki Okumura, Kaoru Tsujioka
Nilotinib is a second-generation tyrosine kinase inhibitors (TKIs) developed to target the bcr-abl protein for the treatment of chronic myelogenous leukemia (CML). [1] Nilotinib has been described as a well-tolerated drug. The most common non-hematologic side effects are skin rash, pruritus, headache, nausea, and fatigue. Cases of panniculitis induced by the other bcr-able TKIs such as imatinib, dasatinib and ponatinib were rarely described in the literature.[2-5] However, a case of panniculitis induced by nilotinib has not been reported...
March 20, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28316033/cardiovascular-complications-of-targeted-therapies-for-chronic-myeloid-leukemia
#3
REVIEW
Rongras Damrongwatanasuk, Michael G Fradley
The development of tyrosine kinase inhibitors (TKIs) dramatically changed the treatment landscape for many different cancers including chronic myeloid leukemia (CML). With the introduction of imatinib, the first TKI developed and approved to effectively treat CML, patient survival has increased dramatically and, in some cases, this fatal cancer can be managed as a chronic disease. Since the approval of imatinib in 2002, four additional TKIs have been developed to treat this disease including the second-generation TKIs nilotinib, dasatinib, and bosutinib and the third-generation TKI ponatinib...
April 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28301600/the-hdac-inhibitor-sb939-overcomes-resistance-to-bcr-abl-kinase-inhibitors-conferred-by-the-bim-deletion-polymorphism-in-chronic-myeloid-leukemia
#4
Muhammad Rauzan, Charles T H Chuah, Tun Kiat Ko, S Tiong Ong
Chronic myeloid leukemia (CML) treatment has been improved by tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) but various factors can cause TKI resistance in patients with CML. One factor which contributes to TKI resistance is a germline intronic deletion polymorphism in the BCL2-like 11 (BIM) gene which impairs the expression of pro-apoptotic splice isoforms of BIM. SB939 (pracinostat) is a hydroxamic acid based HDAC inhibitor with favorable pharmacokinetic, physicochemical and pharmaceutical properties, and we investigated if this drug could overcome BIM deletion polymorphism-induced TKI resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28287043/healthcare-and-economic-burden-of-adverse-events-among-patients-with-chronic-myelogenous-leukemia-treated-with-bcr-abl1-tyrosine-kinase-inhibitors
#5
Jay Lin, Dinara Makenbaeva, Melissa Lingohr-Smith, Robyn Bilmes
OBJECTIVES: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are established treatments for chronic myelogenous leukemia (CML); however, they are associated with infrequent, but clinically serious adverse events (AEs). The objective of this analysis was to assess healthcare resource utilization and costs associated with AEs, previously identified using the FDA Adverse Event Reporting System (FAERS) in another study, among TKI-treated patients. METHODS: Adult patients with ≥1 inpatient or ≥2 outpatient ICD-9-CM diagnosis codes for CML and ≥1 claim for a TKI treatment between January 1, 2006 and September 30, 2012 were identified from the Commercial and Medicare MarketScan databases...
March 12, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28287008/the-value-of-open-access-and-a-patient-centric-approach-to-oral-oncolytic-utilization-in-the-treatment-of-chronic-myelogenous-leukemia-a-u-s-perspective
#6
Lopamudra Das, Matthew Gitlin, Lisa R Siegartel, Dinara Makenbaeva
Since the introduction of tyrosine kinase inhibitors (TKIs), the treatment of patients with chronic myelogenous leukemia (CML) has resulted in significant improvement in patient survival but at a higher pharmaceutical cost to payers. The recent introduction of generic imatinib presents an opportunity to lower pharmacy costs within a population that is growing due to improved survival. Recent literature has focused on the likely benefits to payers of step therapy through generic imatinib. Areas covered: This review provides a perspective that is broader than the evaluation of financial savings or narrowly defined health economic metrics by incorporating factors such as CML patient heterogeneity, including varying levels of disease progression risk, comorbidities, and genetic mutation status, differences in TKI product profiles, clinical guideline recommendations, and the importance of individualized patient care...
March 13, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28286612/characterization-of-patients-with-chronic-myeloid-leukemia-unresponsive-to-tyrosine-kinase-inhibitors-who-underwent-allogeneic-hematopoietic-stem-cell-transplantation
#7
Franceli Ramos Carvalho, Joice Zuckermann, Alessandra Paz, Gustavo Fischer, Liane Esteves Daudt, Lisandra Della Costa Rigoni, Lúcia Silla, Laura Fogliatto, Simone Martins de Castro, Diogo André Pilger
Background: Tyrosine kinase inhibitors (TKIs) were the first drugs to use an intracellular signaling molecule as a therapeutic target. Unresponsiveness to TKIs limits therapeutic options, making allogeneic hematopoietic stem cell transplantation (HSCT) the only option leading to molecular remission. The aim of this study is to characterize CML patients unresponsive to first- and/or second-generation TKI therapy who underwent HSCT and to describe the main factors associated with treatment failure. Subjects and Methods: Twenty one CML patients who underwent allogeneic HSCT and had previously used first- and/or second-generation TKIs from January 2005 to May 2014...
January 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28278078/presence-of-novel-compound-bcr-abl-mutations-in-late-chronic-and-advanced-phase-imatinib-sensitive-cml-patients-indicates-their-possible-role-in-cml-progression
#8
Afia Muhammad Akram, Zafar Iqbal, Tanveer Akhtar, Ahmed Mukhtar Khalid, Muhammad Farooq Sabar, Mahmood Hussain Qazi, Zeba Aziz, Nadia Sajid, Aamer Aleem, Mahmood Rasool, Muhammad Asif, Saleh Aloraibi, Khaled Aljamaan, Mudassar Iqbal
BCR-ABL kinase domain (KD) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-KD mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders...
February 21, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28273190/-novelties-and-experience-with-tyrosine-kinase-inhibitor-therapy-in-chronic-myeloid-leukemia
#9
Júlia Gaál-Weisinger, Orsolya Mucsi, Gábor Körösmezey, Balázs Szili, Hanna Eid, Richárd Kiss, Csaba Bödör, Ilona Tárkányi, Zsolt Nagy, Judit Demeter
The introduction of tyrosine kinase inhibitor (TKI) treatment has resulted in dramatically improved survival in chronic myeloid leukemia (CML). With the new generation of TKIs the majority of patients reach optimal molecular response. Due to the improving survival and the need for lifelong treatment, the safety profile of the various TKIs and the comorbidities of patients have to be considered. More than half of our CML patients had comorbidities that could have influenced the choice of therapy. Because of the high prevalence of cardiovascular comorbidities, cardiovascular risk assessment plays an important role in the care of CML patients...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28271997/a-retrospective-study-of-clinical-profile-and-long-term-outcome-to-imatinib-mesylate-alone-in-childhood-chronic-myeloid-leukemia-in-chronic-phase
#10
(no author information available yet)
OBJECTIVE: Chronic myeloid leukemia (CML) is relatively rare malignancy in childhood. There are limited studies of use of Imatinib Mesylate (IM) alone in management of CML in this age group. METHOD: We retrospectively analyzed the outcome of 30 consecutive children with CML chronic phase treated with IM alone. RESULTS: The median age at the time of diagnosis was 11 years with male preponderance. Asthenia and abdominal discomfort due to splenomegaly were the most common presenting features and splenomegaly a dominant sign...
January 2017: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28259737/medication-adherence-molecular-monitoring-and-clinical-outcomes-in-patients-with-chronic-myelogenous-leukemia-in-a-large-hmo
#11
Reina Haque, Jiaxiao Shi, Joanie Chung, Xiaoqing Xu, Chantal Avila, Christopher Campbell, Syed A Ahmed, Lei Chen, Joanne E Schottinger
OBJECTIVE: Our objective was to examine the association between adherence to tyrosine kinase inhibitors (TKIs) and molecular monitoring and the risk of disease progression or mortality among patients with chronic phase chronic myeloid leukemia (CML). DESIGN: We assembled a retrospective cohort of patients with CML (chronic phase, no prior cancer history, and confirmed to be Philadelphia chromosome positive) using data from electronic health records and chart reviews...
March 1, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28253536/myeloid-neoplasms-with-concurrent-bcr-abl1-and-cbfb-rearrangements-a-series-of-10-cases-of-a-clinically-aggressive-neoplasm
#12
Alireza Salem, Sanam Loghavi, Guilin Tang, Yang O Huh, Elias J Jabbour, Hagop Kantarjian, Wei Wang, Shimin Hu, Rajyalakshmi Luthra, L Jeffrey Medeiros, Joseph D Khoury
Chronic myeloid leukemia (CML) is defined by the presence of t(9;22)(q34;q11.2)/BCR-ABL1. Additional chromosomal abnormalities confer an adverse prognosis and are particularly common in the blast phase of CML (CML-BP). CBFB rearrangement, particularly CBFB-MYH11 fusion resulting from inv(16)(p13.1q22) or t(16;16)(p13.1;q22), is an acute myeloid leukemia (AML)-defining alteration that is associated with a favorable outcome. The co-occurrence of BCR-ABL1 and CBFB rearrangement is extremely rare, and the significance of this finding remains unclear...
March 2, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28251350/variables-associated-with-patient-reported-outcomes-in-persons-with-chronic-myeloid-leukemia-receiving-tyrosine-kinase-inhibitor-therapy
#13
Qian Jiang, Hai-Bo Wang, Lu Yu, Robert Peter Gale
PURPOSE: Explore patient-reported outcomes (PROs), including health-related quality of life (HRQoL), satisfaction with therapy, impact of the therapy on work and daily life, and concerns related to the therapy and identify variables associated with PROs in persons with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitors (TKIs). METHODS: Across-sectional questionnaire was distributed to adults with chronic phase CML and answered anonymously. SF-36 Health Survey was used to measure HRQoL...
March 1, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28241101/does-the-frequency-of-molecular-monitoring-after-tyrosine-kinase-inhibitor-discontinuation-affect-outcomes-of-patients-with-chronic-myeloid-leukemia
#14
Jee Hyun Kong, Elliott F Winton, Leonard T Heffner, Zhengjia Chen, Amelia A Langston, Brittany Hill, Martha Arellano, Fuad El-Rassi, Audrey Kim, Anand Jillella, Vamsi K Kota, Imre Bodó, Hanna Jean Khoury
BACKGROUND: To the authors' knowledge, the optimal frequency of monitoring after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic myeloid leukemia (CML) has not been established. Data regarding the discontinuation of second-generation TKIs used in first-line treatment or after the failure of first-line treatment with TKIs are limited. Herein, the authors report real-world experience with "reduced frequency" molecular monitoring in patients with CML in all phases who discontinued treatment with imatinib, dasatinib, or bosutinib...
February 27, 2017: Cancer
https://www.readbyqxmd.com/read/28209750/stopping-second-generation-tkis-in-cml
#15
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
#16
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
#17
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
#18
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
#19
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...
April 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
#20
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
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