scholarly journals Nilotinib-Induced Acute Pancreatitis in a Patient with Chronic Myeloid Leukemia

2017 ◽  
Vol 11 (2) ◽  
pp. 344-347 ◽  
Author(s):  
Vihang Patel ◽  
Anil Pattisapu ◽  
Karim Attia ◽  
John Weiss
Keyword(s):  
Acute Pancreatitis ◽  
Adverse Event ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Elderly Woman ◽  
Kinase Inhibitor ◽  
Therapeutic Class ◽  
Imatinib Resistant ◽  
Life Threatening ◽  
Novel Drug

Nilotinib, a second-generation tyrosine kinase inhibitor, is used for treatment of chronic myeloid leukemia (CML); it has been widely used especially for imatinib-resistant CML. Despite being a novel drug in this therapeutic class, it has the potential to be harmful. We present the case of an elderly woman who developed life-threatening acute pancreatitis as an adverse event after having started the drug. There is only one reported case in the literature of nilotinib-induced acute pancreatitis. The purpose of this case report is to educate physicians who prescribe this medication to be aware of potential life-threatening adverse events. As more and more therapies are available, physicians should be aware of potential effects of cancer treatment that could be life-threatening to patients.

Lupus-like symptoms with anti-RNP/Sm and anti-nuclear antibodies positivity: An extremely rare adverse event of dasatinib

2019 ◽  
Vol 26 (3) ◽  
pp. 738-741 ◽  
Author(s):  
Senem Maral ◽  
Sule Mine Bakanay ◽  
Orhan Kucuksahin ◽  
Imdat Dilek
Keyword(s):  
Adverse Event ◽  
Pulmonary Arterial Hypertension ◽  
Pleural Effusion ◽  
Chronic Myeloid Leukemia ◽  
Pericardial Effusion ◽  
Arterial Hypertension ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Pulmonary Arterial ◽  
Dasatinib Treatment

Introduction Dasatinib is a potent tyrosine-kinase inhibitor which is used for chronic myeloid leukemia treatment. Pleural effusion is a frequent side effect in patients during dasatinib treatment. Pulmonary arterial hypertension is a rare and life-threatening adverse event of dasatinib. The relationship between dasatinib and autoimmune disorders is unclear, but there are reports of possible mechanisms that have triggered autoimmunity by dasatinib. Case report A 53-year-old male was diagnosed with chronic myeloid leukemia and initiated imatinib mesylate as a treatment. Imatinib was changed to dasatinib as the patient was unresponsive in the first year of treatment. In the fourth year of dasatinib when chronic myeloid leukemia was in both hematological and cytogenetical remission, the patient presented with bilateral massive exudative pleural effusion. Echocardiography was consistent with pericardial effusion with right ventricle enlargement and normal left-side cardiac function. Pulmonary arterial hypertension was diagnosed with high systolic pulmonary arterial pressure. When he had fever and arthralgia, further investigation showed positivity of anti-nuclear antibodies (1/160 titer) and anti-RNP/Sm, which have high specificity for the diagnosis of Systemic Lupus Erythematosus (SLE). Management and outcome Dasatinib was discontinued and nilotinib was initiated. As the pleural effusion persisted despite diuretics and methylprednisolone, mycophenolate mofetil was initiated as a steroid-sparing immune-suppressive agent. The lupus-like symptoms disappeared, and antibodies became undetectable after dasatinib discontinuation. Pericardial effusion improved and pleural effusion did not relapse. Discussion Screening for auto-antibodies may be recommended for patients with a history or symptoms of autoimmune disease before starting dasatinib. All patients who develop pleural effusion while on dasatinib treatment should be investigated for antibodies for lupus.

Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy

Blood ◽  
2006 ◽  
Vol 109 (6) ◽  
pp. 2303-2309 ◽  
Author(s):  
Andreas Hochhaus ◽  
Hagop M. Kantarjian ◽  
Michele Baccarani ◽  
Jeffrey H. Lipton ◽  
Jane F. Apperley ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Treatment Options ◽  
Chronic Phase ◽  
Imatinib Resistance ◽  
Imatinib Resistant ◽  
Dose Modifications

AbstractAlthough imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013.

scholarly journals Spectrum of BCR-ABL Mutations and Treatment Outcomes in Ethiopian Imatinib-Resistant Patients With Chronic Myeloid Leukemia

2021 ◽  
pp. 1187-1193
Author(s):  
Fisihatsion Tadesse ◽  
Getahun Asres ◽  
Abdulaziz Abubeker ◽  
Amha Gebremedhin ◽  
Jerald Radich
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Disease Progression ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Therapy Resistance ◽  
Common Mechanism ◽  
Second Line ◽  
Imatinib Resistance ◽  
Advanced Phase ◽  
Imatinib Resistant

PURPOSE Despite the successes achieved in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy, resistance remains an obstacle. The most common mechanism of resistance is the acquisition of a point mutation in the BCR-ABL kinase domain. Few studies have reported African patients with CML in regard to such mutations. We here report the types of BCR-ABL mutations in Ethiopian imatinib-resistant patients with CML and their outcome. PATIENTS AND METHODS Patients with CML with a diagnosis of imatinib resistance who were tested for BCR-ABL mutation between 2014 and September 2019 were included. RESULTS A total of 962 cases of CML on imatinib therapy were reviewed and 164 cases of failure were found. Of these, only 31 cases (19%) had mutation analysis performed. Most cases (94%) were secondary failures. At the time of CML diagnosis, the median age was 33 years and the majority presented with features of advanced-phase disease. Of the 31 patients, 22 mutations were found (65%). The types of mutations detected were as follows: non–P-loop mutations 36% (11), P-loop mutations 13% (four), and alternatively spliced BCR-ABL variants 23% (seven). The splice variant frequently detected was BCR-ABL35INS (20%). Twenty-six of the 31 patients (84%) were switched to second-line TKIs, whereas in four patients (13%), imatinib dose escalation was done. Overall, the outcome revealed that 16 patients (52%) were alive with complete hematologic response, whereas 12 patients (39%) had died. All patients who expressed BCR-ABL135INS were treated with second-line TKIs, and two of them (33%) had died because of disease progression. CONCLUSION In Ethiopia, CML affects the young and point mutations were frequently detected in imatinib-resistant patients. BCR-ABL1 35INS was also prevalent and associated with disease progression.

scholarly journals Quantitative Proteomic Analysis of Plasma Exosomes to Identify the Candidate Biomarker of Imatinib Resistance in Chronic Myeloid Leukemia Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Mei-Yong Li ◽  
Cui Zhao ◽  
Lian Chen ◽  
Fang-Yi Yao ◽  
Fang-Min Zhong ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Proteomic Analysis ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Life Quality ◽  
Main Function ◽  
Label Free ◽  
Bioinformatics Analyses ◽  
Imatinib Resistance ◽  
Imatinib Resistant

BackgroundImatinib (IM), a tyrosine kinase inhibitor (TKI), has markedly improved the survival and life quality of chronic myeloid leukemia (CML) patients. However, the lack of specific biomarkers for IM resistance remains a serious clinical challenge. Recently, growing evidence has suggested that exosome-harbored proteins were involved in tumor drug resistance and could be novel biomarkers for the diagnosis and drug sensitivity prediction of cancer. Therefore, we aimed to investigate the proteomic profile of plasma exosomes derived from CML patients to identify ideal biomarkers for IM resistance.MethodsWe extracted exosomes from pooled plasma samples of 9 imatinib-resistant CML patients and 9 imatinib-sensitive CML patients by ultracentrifugation. Then, we identified the expression levels of exosomal proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS) based label free quantification. Bioinformatics analyses were used to analyze the proteomic data. Finally, the western blot (WB) and parallel reaction monitoring (PRM) analyses were applied to validate the candidate proteins.ResultsA total of 2812 proteins were identified in plasma exosomes from imatinib-resistant and imatinib-sensitive CML patients, including 279 differentially expressed proteins (DEPs) with restricted criteria (fold change≥1.5 or ≤0.667, p<0.05). Compared with imatinib-sensitive CML patients, 151 proteins were up-regulated and 128 proteins were down-regulated. Bioinformatics analyses revealed that the main function of the upregulated proteins was regulation of protein synthesis, while the downregulated proteins were mainly involved in lipid metabolism. The top 20 hub genes were obtained using STRING and Cytoscape, most of which were components of ribosomes. Moreover, we found that RPL13 and RPL14 exhibited exceptional upregulation in imatinib-resistant CML patients, which were further confirmed by PRM and WB.ConclusionProteomic analysis of plasma exosomes provides new ideas and important information for the study of IM resistance in CML. Especially the exosomal proteins (RPL13 and RPL14), which may have great potential as biomarkers of IM resistance.

scholarly journals A Review of the Management of Chronic Myeloid Leukemia with Dasatinib

2009 ◽  
Vol 1 ◽  
pp. CMT.S1167
Author(s):  
Joanna Gora-Tybor ◽  
Tadeusz Robak
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Chronic Phase ◽  
Imatinib Resistant ◽  
First Choice ◽  
Multitargeted Tyrosine Kinase Inhibitor ◽  
Mutant Forms

Dasatinib is a multitargeted tyrosine kinase inhibitor (TKI), recommended for chronic myeloid leukemia (CML) in chronic, accelerated and blastic phases that are resistant or intolerant to imatinib. The recognition of BCR-ABL gene and corresponding protein with deregulated tyrosine kinase (TK) activity as crucial for malignant transformation in CML, led to synthesis of the small-molecule drugs designed to interfere with Bcr-Abl TK activation. The first TKI introduced into clinical practice in 1998, was imatinib mesylate, which became the first choice drug in chronic phase CML. However, approximately 20%-25% of patients initially successfully treated with imatinib, develop resistance to this drug, mainly because of selection of clones expressing mutant forms of BCR-ABL with impairing imatinib binding. Dasatinib is 325-fold more potent than imatinib against cell expressing wild-type BCR-ABL and showing activity against most imatinib-resistant Bcr-Abl mutants. Several clinical trials demonstrated that dasatinib is effective and generally well tolerated in imatinib resistant or intolerant CML and represents a promising therapeutic option for these patients.

scholarly journals Dasatinib-Induced Hypopigmentation in Pediatric Patient with Chronic Myeloid Leukemia: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Bader Alharbi ◽  
Samer Alamri ◽  
Ahmed Mahdi ◽  
Siham Marghalani
Keyword(s):  
Case Report ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Fluid Retention ◽  
Review Of The Literature ◽  
Dermatology Clinic ◽  
Imatinib Resistant ◽  
Dasatinib Treatment ◽  
New Onset

Dasatinib is an oral second-generation multitarget tyrosine-kinase inhibitor (TKI) that is efficacious in treating imatinib-resistant chronic myeloid leukemia (CML) or intolerant cases. Noncutaneous adverse effects with dasatinib are well known in the literature, most commonly cytopenias and fluid retention, while pigmentary abnormalities have rarely been reported. We report the case of a 12-year-old male known case of CML, who presented to dermatology clinic approximately 2 years after initiating dasatinib treatment, with new-onset hypopigmentation of his upper limb, upper chest, and both knees of six months’ duration.

Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis

Blood ◽  
2006 ◽  
Vol 109 (8) ◽  
pp. 3207-3213 ◽  
Author(s):  
Jorge Cortes ◽  
Philippe Rousselot ◽  
Dong-Wook Kim ◽  
Ellen Ritchie ◽  
Nelson Hamerschlak ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Blast Crisis ◽  
Phase 1 ◽  
Src Family Kinases ◽  
Highly Active ◽  
Imatinib Resistant ◽  
Number Of Patients

AbstractThe prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can induce responses in a subset of these patients, resistance to the drug develops rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases. After promising phase 1 results, we report the results of phase 2 clinical trials of dasatinib in patients with imatinib-resistant or -intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up, dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these patients, respectively. Most (86%) of these MCyRs were complete cytogenetic responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively, of MBC- and LBC-CML patients achieving MaHR had not experienced disease progression at the 8-month follow-up. Response rates were similar in patients with and without BCR-ABL mutations known to confer resistance to imatinib. Dasatinib was well tolerated. Nonhematologic adverse events were mild to moderate. Cytopenias were common and could be managed by dose modification. Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015.

Abstract 5389: Novel kinase inhibitor for imatinib-resistant chronic myeloid leukemia with T315I mutation

2015 ◽  
Author(s):  
Soon-Sun Hong ◽  
Soo Jung Kim ◽  
Kyung Hee Jung ◽  
Hong Hua Yan ◽  
Zhenghuan Fang ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Imatinib Resistant ◽  
T315i Mutation

Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4143-4150 ◽  
Author(s):  
Francois Guilhot ◽  
Jane Apperley ◽  
Dong-Wook Kim ◽  
Eduardo O. Bullorsky ◽  
Michele Baccarani ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Severe Neutropenia ◽  
Open Label ◽  
Imatinib Resistance ◽  
Imatinib Resistant

AbstractTreatment options are limited for patients with imatinib-resistant or -intolerant accelerated phase chronic myeloid leukemia (CML-AP). Dasatinib is a novel, potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC-family kinases that showed marked efficacy in a phase 1 trial of patients with imatinib-resistant CML. Results are presented for 107 patients with CML-AP with imatinib-resistance or -intolerance from a phase 2, open-label study further evaluating dasatinib efficacy and safety. At 8 months' minimum follow-up, 81%, 64%, and 39% of patients achieved overall, major (MaHR), and complete hematologic responses, respectively, whereas 33% and 24% attained major and complete cytogenetic remission. Of 69 patients who achieved MaHR, 7 progressed. Seventy-six percent of patients are estimated to be alive and progression-free at 10 months. Response rates for the 60% of patients with baseline BCR-ABL mutations did not differ from the total population. Dasatinib was well tolerated: most nonhematologic adverse events (AEs) were mild to moderate; no imatinib-intolerant patients discontinued dasatinib because of AEs. Although common (76% of patients with severe neutropenia), cytopenias were manageable through dose modification. In summary, dasatinib induced significant hematologic and cytogenetic responses in patients with imatinib resistance or intolerance, was well tolerated, and may represent a potent new therapeutic option for CML-AP. Further follow-up is warranted. This trial was registered at www.clinicaltrials.gov as #CA180005.

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