scholarly journals The Levels of FoxO3a Predict the Failure of Imatinib Mesylate Therapy among Chronic Myeloid Leukemia Patients

2021 ◽  
Vol 9 (B) ◽  
pp. 255-259
Author(s):  
Shinta Oktya Wardhani ◽  
Hani Susanti ◽  
Puji Rahayu ◽  
Yuyun Yueniwati ◽  
Jonny Fajar
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Failure ◽  
Treatment Response ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Effect Estimate ◽  
Forkhead Transcription Factor ◽  
Increased Risk ◽  
Risk Of Treatment

INTRODUCTION: Forkhead Transcription Factor 3a (FoxO3a) has been proposed to have a high efficacy to predict the failure of imatinib mesylate (IM) therapy among Chronic Myeloid Leukemia (CML) patients. However, the limited evidence had made this marker remained controversy. OBJECTIVES: We aimed to investigate the correlation between the levels of FoxO3a and the risk of treatment failure of IM therapy in CML patients. METHODS: A prospective cohort study was carried out between February 2019 and February 2020 in Saiful Anwar Hospital, Malang, Indonesia. All CML patients treated with IM on our hospital during the study period were included. The levels of FoxO3a was determined using the Enzyme-linked immunosorbent assay (ELISA) using Cusabio Biotech Kit (Cusabio Biotech Co., New York, USA). The treatment response was assessed using the European Leukemia criteria. The correlation and effect estimate between the levels of FoxO3a and treatment response of CML patients was assessed using multiple logistic regression. RESULTS: 53 CML patients receiving IM in our hospital were included, consisting of 29 patients with good response and 24 patients with non-response. Our study found that CML patients with lower levels of FoxO3a was associated with increased risk to develop treatment failure when treated with IM. Moreover, we also found that higher risk of treatment failure of IM therapy was also found in patients with increased levels of thrombocytes, basophils, and leukocytes, and lower levels of hemoglobin. CONCLUSION: We reveal that FoxO3a is the prominent marker to predict the treatment response of CML patients treated with IM.

The Association Between the Level of Leukemic Stem Cells and Treatment Response Among Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate

2020 ◽  
Vol 7 (2) ◽  
pp. 119-124
Author(s):  
Shinta Oktya Wardhani ◽  
Hani Susianti ◽  
Puji Rahayu ◽  
Yuyun Yueniwati
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Cross Sectional Study ◽  
Imatinib Therapy ◽  
Sectional Study ◽  
Cross Sectional ◽  
Blast Cells ◽  
Response Group

Background: The failure of imatinib therapy in patients with chronic myeloid leukemia (CML) is associated with the presence of leukemic stem cell (LSC), and the altered LSC level was reported to occur earlier in the progression of CML. Objective: The study aimed to assess the association between the level of LSC and treatment response among CML patients treated with imatinib mesylate. Methods: A cross-sectional study was conducted in Saiful Anwar Hospital. All participants were divided into two groups, response and non-response group. To assess the level of LSC, flow cytometry was conducted conforming with BD Bioscience. The association and effect estimates were determined using multiple logistic regression. Results and Discussion: A total of 29 response and non-response CML patients treated with imatinib therapy were recruited for our study. After six months of imatinib therapy, we found that elevated levels of leukocytes, thrombocytes, basophils, and blast cells were associated with treatment failure among CML patients treated with imatinib. Moreover, we also found that the LSC level was observed significantly higher in the non-response group compared to the response group among CML patients treated with imatinib. Conclusion: Our study reveals that the elevated level of LSC is considered as an important factor to predict the failure of imatinib therapy among CML patients.

scholarly journals Is Adherence to Imatinib Mesylate Treatment among Patients with Chronic Myeloid Leukemia Associated with Better Clinical Outcomes in Qatar?

2016 ◽  
Vol 10 ◽  
pp. CMO.S32822 ◽  
Author(s):  
Nader I. Al-Dewik ◽  
Hisham M. Morsi ◽  
Muthanna M. Samara ◽  
Rola S. Ghasoub ◽  
Cinquea C. Gnanam ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Myeloid Leukemia ◽  
Treatment Failure ◽  
Imatinib Mesylate ◽  
Clinical Outcomes ◽  
Myeloid Leukemia ◽  
Poor Adherence ◽  
Close Monitoring ◽  
Follow Up Study

Background Despite the revolutionary success of introducing tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), for treating chronic myeloid leukemia (CML), a substantial proportion of patients’ treatments fail. Aim This study investigates the correlation between patient adherence and failure of TKIs’ treatment in a follow-up study. Methods This is a follow-up study of a new cohort of CML patients. Adherence to IM is assessed using the Medication Event Monitoring System (MEMS 6 TrackCap, AARDEX Ltd). The 9-item Morisky Medication Adherence Scale, medication possession ratio (MPR) calculation, and the electronic medical records are used for identifying potential factors that influence adherence. Clinical outcomes are assessed according to the European LeukemiaNet 2013 guidelines via reverse transcriptase quantitative polymerase chain reaction measurement of the level of BCR-ABL1 transcripts in peripheral blood. Response is classified at the hematological, cytogenetic, and molecular levels into optimal, suboptimal, or failure. Results A total of 36 CML patients (5 citizens and 31 noncitizen residents) consented to participate in the study. The overall mean MEMS score was 89. Of the 36 patients, 22 (61%) were classified as adherent (mean: 95) and 14 (39%) were classified as nonadherent (mean: 80.2). Adherent patients were significantly more likely to obtain optimal response (95%) compared to the nonadherent group (14.3%; P < 0.0001). The rate of poor adherence was as high as 39% using MEMS, which correlates with 37% treatment failure rate. The survey results show that 97% of patients increased the IM dose by themselves when they felt unwell and 31% of them took the missing IM dose when they remembered. Other factors known to influence adherence show that half of patients developed one or more side effects, 65% of patients experienced lack of funds, 13% of patients declared unavailability of the drug in the NCCCR pharmacy, and 72% of patients believed that IM would cure the disease. The MPR results reveal that 16% of patients had poor access to treatment through the hospital pharmacy. Discussion and Conclusion This is the first prospective study to evaluate CML patients’ adherence and response to IM in Qatar. The high rate of treatment failure observed in Qatar is explained by poor adherence. An economic factor (unaffordable drug prices) is one of the main causes of nonadherence and efforts should be made locally to improve access to medication for cancer diseases. Other risk factors associated with poor adherence could be improved by close monitoring and dose adjustment. Monitoring risk factors for poor adherence and patient education that include direct communication between the health-care teams, doctors, nurses, pharmacists, and patients are essential components for maximizing the benefits of TKI therapy and could rectify this problem. The preliminary results show that patients’ response to treatment may be directly linked to patients’ adherence to treatment. However, further in-depth and specific analysis may be necessary in a larger cohort.

Clinical Relevance of a Pharmacogenetic Approach Using Multiple Candidate Gene Polymorphisms To Predict Response and Resistance to Imatinib Mesylate Therapy in Chronic Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 737-737 ◽  
Author(s):  
Dong Hwan (Dennis) Kim ◽  
Lakshmi Sriharsha ◽  
Wei Xu ◽  
Suzanne Kamel-Reid ◽  
Xiangdong Liu ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Failure ◽  
Candidate Gene ◽  
Imatinib Mesylate ◽  
Dose Escalation ◽  
Myeloid Leukemia ◽  
Candidate Gene Approach ◽  
Advanced Stage ◽  
Cancer Resistance ◽  
The Impact

Abstract Background: Imatinib resistance (IR) is a well known cause of treatment failure in chronic myeloid leukemia (CML) patients being treated with imatinib mesylate (IM). Several cellular and genetic mechanisms of IR have been proposed including amplification and overexpression of the BCR-ABL gene, the presence of specific point mutations and MDR1 gene overexpression. Methods: We investigated the impact of 16 single nucleotide polymorphisms (SNPs) in 5 genes potentially associated with pharmacogenetics of IM (ABCB1, multidrug resistance 1; ABCG2, breast-cancer resistance protein; CYP3A5, cytochrome P450 3A5; HOCT1, human organic cation transporter 1; AGP1, alpha-1-acid glycoprotein-1, plasma protein binding to IM). The major endpoints included: response to IM: cytogenetic (CyR) or molecular response (MoR); resistance to IM: loss of response (LOR), treatment-failure (including primary resistance or LOR); progression to accelerated phase (AP) or blast crisis (BC), or death; and need for IM dose escalation to overcome resistance or LOR. The DNAs from peripheral blood samples were genotyped using the Sequenom MassARRAY system based on MALDI-TOF technique. The study population included 229 patients whose clinical outcomes following IM therapy were evaluated from January 2000 to January 2007 (male:female 96:133; median age at start of IM, 53 years-old; white:non-white 170:59; chronic phase:AP:BC, 199:23:3). Results: The frequencies of genotypes in 16 SNPs are summarized in Table 1. The GG allele in ABCG2 (rs2231137), AA allele in CYP3A5 (rs776746) and advanced stage were significantly associated with poor response to IM, while GG allele at HOCT1 (rs683369) and advanced stage correlated with high rate of LOR or treatment failure. The CC allele in ABCG2 (rs2231142) was also identified as an independent predictor of more frequent need for IM dose escalation. The results of multivariate analyses are summarized in Table 2. Conclusion: Using a novel, multiple candidate gene approach based on the pharmacogenetics of Imatinib mesylate, we identified several SNP candidates in patients with CML that are potential predictors of clinical response to IM (rs2231137, ABCG2 or rs776746, CYP3A5), resistance to IM (rs683369, HOCT1) and need for IM dose escalation (rs2231142, ABCG2). Further studies are warranted to validate the role of these SNPs in the early identification of individuals with CML who may not respond optimally to standard IM therapy. Table 1. The genotype frequency and clinical significance in 16 SNPs Table 2. Multivariate regression model based on Cox's proportional hazard model for each-point

Effects of GSTP1 Ile105Val polymorphism on both susceptibility and treatment response of chronic myeloid leukemia

Meta Gene ◽  
2021 ◽  
Vol 28 ◽  
pp. 100865
Author(s):  
Ait Boujmia Oum Kaltoum ◽  
Dehbi Hind ◽  
Qachouh Meryem ◽  
Kassogue Yaya ◽  
Nadifi Sellama ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Myeloid Leukemia ◽  
Gstp1 Ile105val
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