Cutaneous side effects in a cohort of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: General description and further characterization, correlation with photoexposition and study of hypopigmentation as treatment's prognostic factor

2020 ◽  
Vol 33 (6) ◽  
Author(s):  
Mar Llamas‐Velasco ◽  
Enrique Ovejero‐Merino ◽  
Amaro García‐Diez ◽  
Luis Requena ◽  
Esteban Daudén ◽  
...  
Keyword(s):  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Prognostic Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
General Description ◽  
Cutaneous Side Effects

scholarly journals Side effects and medication adherence of tyrosine kinase inhibitors for patients with chronic myeloid leukemia in Taiwan

Medicine ◽  
2018 ◽  
Vol 97 (26) ◽  
pp. e11322 ◽  
Author(s):  
Yu-Fen Tsai ◽  
Wen-Chuan Huang ◽  
Shih-Feng Cho ◽  
Hui-Hua Hsiao ◽  
Yi-Chang Liu ◽  
...  
Keyword(s):  
Medication Adherence ◽  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors

scholarly journals Patient Preferences for Stopping Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4274-4274
Author(s):  
Rachel MA Kyle ◽  
Alejandro Lazo-Langner ◽  
Anargyros Xenocostas ◽  
Ian H. Chin-Yee ◽  
Kang Howson-Jan ◽  
...  
Keyword(s):  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Relapse Rate ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Interquartile Range ◽  
Median Response ◽  
Tki Treatment

Abstract Abstract 4274 Introduction: After the introduction of tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) became the first cancer with a medical treatment that affords patients a normal lifespan. First-line treatment includes one of the three approved TKIs with regular molecular monitoring. Several reports have described individuals stopping imatinib and remaining in complete molecular response (CMR). There are currently several ongoing randomized clinical trials evaluating the safety of stopping TKI treatment in patients with a sustained CMR. In 2010 the preliminary results from the STIM (STop IMatinib) trial (Mahon, Lancet Oncology), were published. Results showed that 38% of patients had a sustained CMR after 2 years off TKI treatment and the remaining 62% who relapsed responded to restarting their previous TKI treatment. As this research will potentially influence clinical practice in the near future, we aimed to explore patient reactions, preferences and risk acceptability of stopping TKI treatment. With that in mind we conducted an interview-assisted survey of CML patients seen at a single tertiary care centre. Methods: We included CML patients with cytogenetic and molecular Ph+ chromosome confirmation currently being treated with a TKI. Patients were approached during regular follow-up appointments. A survey was conducted through structured interviews using a standard form. Patients' preferences were explored through a case-based scenario using Visual Analog Scales ranging from 0 to 100% or 5-point Likert scales ranging from “absolutely stop” (1) to “absolutely not stop” (5). A trained interviewer asked the survey questions and was able to clarify questions that were unclear to the participant. Data was analyzed using proportions for dichotomous variables and medians and interquartile ranges for continuous variables. 95% confidence intervals for the proportions were calculated using the normal approximation interval. Results: Interviews were conducted between June and August 2012 at the London Regional Cancer Program (LRCP) in London, Ontario. 38 out of 40 (95%) CML patients approached completed the survey. Mean age of participants was 51 years old and 47% were male. 37% of participants had not finished high school and another 37% had completed college/university/trade school. Participants had a diagnosis of CML for an average of 50 months prior to enrollment. The majority (21/38 participants, 55%) were taking imatinib, with 11 (29%) on nilotinib and 6 (16%) on dasatinib. 71% (95% CI ± 14%) of the participants said that taking their medications daily was “simple and easy and they were able to remember 100% of the time.” 26% reported daily side effects while 24% reported never experiencing side effects from their TKI. 79% (95% CI ± 13%) of the participants said that they have never considered stopping the drug based on the side effects that they experience. 61% of participants responded that fear of the disease going out of control keeps them taking their TKI (95% CI ± 16%), whereas 34% responded that it is their doctor's strong recommendation that motivates them (95% CI ± 15%). When asked what risk of relapse after stopping the TKI they would be willing to accept the median response was a 25% relapse rate (interquartile range 20–50). When responding to the same question after informing the participant that all patients have responded to restarting TKIs the median response increased to a 35% relapse rate (interquartile range 20–60). When given a relapse rate of 20% and a likert scale ranging from “absolutely stop” to “absolutely not stop,” the median response was “likely stop” with the 25th and 75th interquartile ranges being “absolutely stop” and “likely not stop” respectively. When the published relapse rate of 60% was given, however, the median was “likely not stop” with the 25th interquartile range at “neutral to stopping” and 75thinterquartile range at “absolutely not stop.” Discussion: This data suggests that the majority of participants perceive little difficulty with taking their TKI regularly and have never considered stopping it. Two major determinants on participant's decisions are fear of the disease going out of control and their physician's influence. Further, with the published rate of relapse after stopping TKI treatment the majority of individuals would choose to continue taking their medications for CML. Disclosures: Lazo-Langner: LeoPharma: Honoraria; Pfizer: Honoraria. Hsia:Novartis: Participant in Advisory Board Other.

A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

scholarly journals Thrombotic microangiopathy in dasatinib-treated patients with chronic myeloid leukemia

2019 ◽  
Vol 4 (1-2) ◽  
pp. 41-45 ◽  
Author(s):  
Takeo Koshida ◽  
Sylvia Wu ◽  
Hitoshi Suzuki ◽  
Rimda Wanchoo ◽  
Vanesa Bijol ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Thrombotic Microangiopathy ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kidney Biopsy ◽  
Kinase Inhibitor ◽  
Target Effect

Dasatinib is the second-generation tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia. Proteinuria has been reported with this agent. We describe two kidney biopsy–proven cases of dasatinib-induced thrombotic microangiopathy that responded to stoppage of dasatinib and using an alternate tyrosine kinase inhibitor. Certain specific tyrosine kinase inhibitors lead to endothelial injury and renal-limited thrombotic microangiopathy. Hematologists and nephrologists need to be familiar with this off-target effect of dasatinib.

Bosutinib in the real‐life treatment of chronic myeloid leukemia patients aged >65 years resistant/intolerant to previous tyrosine‐kinase inhibitors

2021 ◽  
Author(s):  
Roberto Latagliata ◽  
Immacolata Attolico ◽  
Malgorzata Monika Trawinska ◽  
Isabella Capodanno ◽  
Mario Annunziata ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Real Life ◽  
The Real

scholarly journals Inhibition of Xanthine Oxidoreductase Enhances the Potential of Tyrosine Kinase Inhibitors against Chronic Myeloid Leukemia

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 74 ◽  
Author(s):  
Marta Romo-González ◽  
Sara Moreno-Paz ◽  
Violeta García-Hernández ◽  
Fermín Sánchez-Guijo ◽  
Ángel Hernández-Hernández
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Single Agent ◽  
Signaling Cascade ◽  
Xanthine Oxidoreductase

Chronic myeloid leukemia (CML) is characterized by the expression of the oncogenic kinase BCR-ABL. Although tyrosine kinase inhibitors (TKIs) against BCR-ABL represent the standard therapeutic option for CML, resistances to TKIs can be a serious problem. Thus, the search for novel therapeutic approaches is still needed. CML cells show an increased ROS production, which is required for maintaining the BCR-ABL signaling cascade active. In line with that, reducing ROS levels could be an interesting therapeutic strategy for the clinical management of resistant CML. To analyze the therapeutic potential of xanthine oxidoreductase (XOR) in CML, we tested the effect of XOR inhibitor allopurinol. Here, we show for the first time the therapeutic potential of allopurinol against BCR-ABL-positive CML cells. Allopurinol reduces the proliferation and clonogenic ability of the CML model cell lines K562 and KCL22. More importantly, the combination of allopurinol with imatinib or nilotinib reduced cell proliferation in a synergistic manner. Moreover, the co-treatment arms hampered cell clonogenic capacity and induced cell death more strongly than each single-agent arm. The reduction of intracellular ROS levels and the attenuation of the BCR-ABL signaling cascade may explain these effects. Finally, the self-renewal potential of primary bone marrow cells from CML patients was also severely reduced especially by the combination of allopurinol with TKIs. In summary, here we show that XOR inhibition is an interesting therapeutic option for CML, which can enhance the effectiveness of the TKIs currently used in clinics.

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