Persistent neutropenia in chronic myelogenous leukemia in chronic phase treated with imatinib mesylate

Hwang, Y.; Tse, Eric; So, Jason C. C.; Wan, T. S. K.; Kwong, Yok–Lam

doi:10.1002/ajh.21383

Cited by 4 publications

(5 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Administration of G‐CSF in patients B and C might have accelerated neutrophil regeneration . In patients with CML, G‐CSF has been shown to be effective in overcoming imatinib‐induced neutropenia . In this way, recovery of neutrophil counts can even be achieved during uninterrupted imatinib therapy.…”

Section: Discussionmentioning

confidence: 99%

Imatinib-induced agranulocytosis in patients with gastrointestinal stromal tumors

Farag

Verschoor

Bosma

et al. 2015

The Journal of Clinical Pharmacology

View full text Add to dashboard Cite

Agranulocytosis is a rare but serious side effect of imatinib in gastrointestinal stromal tumor (GIST) patients. Imatinib is an inhibitor of the proto-oncogene tyrosine kinase (c-kit) and the first-line agent in patients with locally advanced and metastatic GIST. Little evidence is available on the management of this adverse event, and consensus-based guidelines are lacking. In this article, we describe 4 patients with agranulocytosis after starting imatinib. In addition, an overview of the available literature concerning the underlying mechanisms is given, and therapeutic strategies for overcoming this adverse event are discussed. In our experience it appears safe to restart imatinib after normalization of neutrophil count. In case of relapse of agranulocytosis, reintroduction combined with prednisolone, with treatment with granulocyte colony-stimulating factor or dose reduction can be considered.

show abstract

Section: Discussionmentioning

confidence: 99%

Imatinib-induced agranulocytosis in patients with gastrointestinal stromal tumors

Farag

Verschoor

Bosma

et al. 2015

The Journal of Clinical Pharmacology

View full text Add to dashboard Cite

show abstract

“…The reduced effectiveness of imatinib monotherapy beside its immunosuppressive action led to recurrent dose interruption and thus compromised patient outcome . Perhaps, combining anticancer drugs with natural micronutrients presents an advantage.…”

Section: Discussionmentioning

confidence: 99%

“…However, c‐kit mutation and over‐expression associated with pro‐angiogenic and anti‐apoptotic responses resulted in compromised imatinib cytotoxicity and development of imatinib‐resistant cancer cells . It has also been reported that 45% of imatinib‐treated patients experienced severe neutropenia requiring interruption of therapy or dose reduction ending in compromising patient outcome . Thereby, several reports have described reduced effectiveness of imatinib as single agent for successful chemotherapy .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Modulation of Imatinib Cytotoxicity by Selenite in HCT116 Colorectal Cancer Cells

Abdel-Aziz

Azab

Youssef³

et al. 2014

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Imatinib is a principal therapeutic agent for targeting colorectal tumours. However, mono-targeting by imatinib does not always achieve complete cancer eradication. Selenite, a well-known chemopreventive agent, is commonly used in cancer patients. In this study, we aimed to explore whether selenite can modulate imatinib cytotoxicity in colorectal cancer cells. HCT116 cells were treated with different concentrations of imatinib and/or selenite for 24, 48 and 72 hr. Imatinib-selenite interaction was analysed using isobologram equation. As indicators of apoptosis, DNA fragmentation, caspase-3 activity, Bcl-2 expression were explored. Autophagic machinery was also checked by visualizing acidic vesicular organelles and measuring Beclin-1 expression. Furthermore, reactive oxygen and nitrogen species were also examined. This study demonstrated that selenite synergistically augmented imatinib cytotoxicity in HCT116 cells as demonstrated by combination and dose reduction indices. Supranutritional dose of selenite when combined with imatinib induced apoptotic machinery by decreasing Bcl-2 expression, increasing caspase-3 activity and subsequently fragmenting DNA and blunted cytoprotective autophagy by decreasing Beclin-1 expression and autophagosomes formation. Moreover, their combination induced cell cycle S-phase block, increased total thiol content and reduced nitric oxide levels. In conclusion, selenite synergizes imatinib cytotoxicity through multi-barrelled molecular targeting, providing a novel therapeutic approach for colorectal cancer.Colorectal cancer (CRC) is the third most commonly diagnosed tumour type in males and the second in females worldwide [1]. Its annual incidence is expected to increase by nearly 80% over the next two decades in the less developed countries [2]. Imatinib mesylate, a tyrosine kinase small molecule inhibitor, has been studied for its therapeutic efficacy in the treatment of gastrointestinal stromal tumours (GISTs) [3] and CRC [4]. It was proven that imatinib inhibits chronic myeloid leukaemia (CML)-specific tyrosine kinase BCR-ABL and stem cell factor receptor (c-kit) [4]. However, c-kit mutation and over-expression associated with pro-angiogenic and anti-apoptotic responses resulted in compromised imatinib cytotoxicity and development of imatinib-resistant cancer cells [5,6]. It has also been reported that 45% of imatinib-treated patients experienced severe neutropenia requiring interruption of therapy or dose reduction ending in compromising patient outcome [7]. Thereby, several reports have described reduced effectiveness of imatinib as single agent for successful chemotherapy [4,7,8].The search for the underlying resistance mechanisms of imatinib has revealed that several interplaying mechanisms play vital roles. Although BCR/ABL point mutation, amplification and over-expression are frequently involved in imatinib and other tyrosine kinase inhibitors' resistance mechanisms [9], many other BCR/ABL-independent factors have been identified. These include decreased intracellu...

show abstract

“…As per Yu-Yan Hwang et al, persistent neutropenia was observed after imatinib treatment. [66] SAWYERS et al patients treated with 400 mg and 600 mg of imatinib, most common grade 4 abnormalities was neutropenia. [50] As per N. Singhal et al, neutropenia is the most common side effect of imatinib treatment.…”

Section: Neutrophilsmentioning

confidence: 99%

Study on Mutation Resistance to Imatinib in Chronic Myeloid Leukemia Patients from West India

Darji¹,

Bharadia²

2021

SJAC

View full text Add to dashboard Cite

Imatinib is a type of protein tyrosine kinase inhibitor which inhibits the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome i.e. the BCR-ABL tyrosine kinase, abnormality in CML patient. The aim of the study is to assess the response of imatinib in CML patients and to observe resistance to imatinib. Study was performed at Ahmedabad, Gujarat, India. Dose of 400, 600, 800 mg of Imatinib was found to be prescribed to all patients during the study. Comparison of laboratory parameters and PCR data were done after measurement by RT-PCR method. Total 256 patients with CML were enrolled in the study. 196 patients had completed study as per protocol. 38 patients were newly diagnosed whereas 158 patients were already diagnosed with CML. 89.29% (n = 175) of patients achieved complete haematological response, Complete MolR were achieved in n = 41 at 6 th months, n = 1 at 12 th month & 18 th month and no patient was found with none CyR out of 196 patients; no patient were found with minimal CyR at 6 th month, 2 patient were at 12 th month and 3 patients were at 18 th month. Mean PCR value (BCR-ABL/ABL ratio) in patient was found 0.245±1.16 at Day 0, 0.824±1.51 at 6 th month, 4.086±9.58 at 12 th month and 6.713±11.32 at 18 th month visit. In conclusion, it was observed that resistance to imatinib might be developed within an average time of 12 months in the patients due to which survival rate was drastically reduced.

show abstract

Persistent neutropenia in chronic myelogenous leukemia in chronic phase treated with imatinib mesylate

Cited by 4 publications

References 22 publications

Imatinib-induced agranulocytosis in patients with gastrointestinal stromal tumors

Imatinib-induced agranulocytosis in patients with gastrointestinal stromal tumors

Modulation of Imatinib Cytotoxicity by Selenite in HCT116 Colorectal Cancer Cells

Study on Mutation Resistance to Imatinib in Chronic Myeloid Leukemia Patients from West India

Contact Info

Product

Resources

About