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[PMID]:29305630
[Au] Autor:Ben Lakhal R; Ghedira H; Bellaaj H; Ben Youssef Y; Menif S; Manai Z; Bedoui M; Lakhal A; M'Sadek F; Elloumi M; Khélif A; Ben Romdhane N; Laatiri MA; Ben Othmen T; Meddeb B
[Ad] Endereço:Hematology Department, Aziza Othmana University Hospital, Tunis, Tunisia. raihane.benlakhal@gmail.com.
[Ti] Título:Chronic myeloid leukemia patients in Tunisia: epidemiology and outcome in the imatinib era (a multicentric experience).
[So] Source:Ann Hematol;97(4):597-604, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology. Response (hematologic, cytogenetic, and molecular responses) and outcome-overall survival (OS), event-free survival (EFS), and progression-free survival (PFS)-were evaluated. The following prognostic factors were analyzed for their impact on the European leukemia net (ELN) response, OS, EFS, and PFS at 5 years: age, sex, leukocyte count, Sokal score, European Treatment and Outcome Study (EUTOS) score, CML phase, time to starting IM, and impact of adverse events. The median age was 45 years (3-85 years). Two hundred ten (51.2%) patients were male. Splenomegaly was present in 322 of the 410 (79%). Additional cytogenetic abnormalities were encountered in 25 (6.3%) patients. At diagnosis, 379 (92.4%) patients were in CP, 31 (7.6%) were in AP. The Sokal risk was low in 87 (22.5%), intermediate in 138 (35.7%), and high in 164 patients (41.9%). The EUTOS risk was low in 217 (74%), and high in 77 (26%) patients. The rates of cumulative complete cytogenetic response (CCyR), major molecular response (MMR), and molecular response 4/5 log (MR4.5) in CP/AP-CML patients were 72, 68.4, and 46.4%, respectively. The median time to reach CCyR, MMR, and MR4.5 was 6 months (3-51), 18 months (3-72), and 24 months (3-100), respectively. According to the ELN criteria, optimal, suboptimal response, and failure were noted in 206 (51.8%), 61 (15.3%), and 125 (31.4%) patients, respectively. Five-year event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) were 81, 90, and 90%, respectively. By multivariate analysis, AP, high EUTOS risk, and baseline WBC ≥ 150G/l remained independent predictive factors of non-optimal response to IM. The adverse events (AE) of IM were moderate and tolerable. With the caveats that the monitoring of the disease was not optimal, response rates were similar to those reported in previous studies. It is clear to us that improvements should be made in treatment of AP-CML and high Sokal risk group of CP-CML. The frontline use of second-generation tyrosine kinase inhibitor (TKI) is expected to improve the results of the first-line treatment of these high-risk Tunisian patients, but cost and accessibility of this therapy remain the problems in developing countries.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Mesilato de Imatinib/uso terapêutico
Leucemia Mieloide de Fase Acelerada/tratamento farmacológico
Leucemia Mieloide de Fase Crônica/tratamento farmacológico
Inibidores de Proteínas Quinases/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/efeitos adversos
Criança
Pré-Escolar
Feminino
Seguimentos
Seres Humanos
Mesilato de Imatinib/efeitos adversos
Leucemia Mieloide de Fase Acelerada/diagnóstico
Leucemia Mieloide de Fase Acelerada/epidemiologia
Leucemia Mieloide de Fase Acelerada/patologia
Leucemia Mieloide de Fase Crônica/diagnóstico
Leucemia Mieloide de Fase Crônica/epidemiologia
Leucemia Mieloide de Fase Crônica/patologia
Masculino
Meia-Idade
Padrões de Prática Médica
Prognóstico
Inibidores de Proteínas Quinases/efeitos adversos
Estudos Retrospectivos
Esplenomegalia/etiologia
Esplenomegalia/patologia
Esplenomegalia/prevenção & controle
Análise de Sobrevida
Carga Tumoral/efeitos dos fármacos
Tunísia/epidemiologia
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 8A1O1M485B (Imatinib Mesylate)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3224-2


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[PMID]:29480823
[Au] Autor:Qiu HB; Zhou ZG; Feng XY; Liu XC; Guo J; Ma MZ; Chen YB; Sun XW; Zhou ZW
[Ad] Endereço:Department of Gastric and Pancreatic Surgery.
[Ti] Título:Advanced gastrointestinal stromal tumor patients benefit from palliative surgery after tyrosine kinase inhibitors therapy.
[So] Source:Medicine (Baltimore);97(2):e9097, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The role of palliative surgery is controversial in advanced gastrointestinal stromal tumors (GIST) after tyrosine kinase inhibitors (TKIs) therapy.We evaluated safety and clinical outcomes in a single institution series of advanced GIST patients from January 2002 to December 2008.One hundred and fifty-six patients had been recruited, including 87 patients underwent surgical resection and 69 patients kept on TKIs treatment. Four patients had major surgical complications. Median follow-up was 38.3 months, the overall survival (OS) and progression-free survival (PFS) of the patients in surgical group were longer than the nonsurgical group, PFS: 46.1 versus 33.8 months (P < .01), OS: 54.8 versus 40.4 months. In the subgroup analysis for the patients received surgery, the median PFS for patients with progression disease, stable disease, and partial response was 33.3, 51.5, and 83.0 months, respectively (P < .01). Median OS was 68.0 months in those with only liver or peritoneal metastases, and 45.3 months in those with both metastases. Median PFS of patients underwent R0/R1 resection was 73.6 months compared with 35.8 months in R2 resection patients (P < .01).Patients with advanced GISTs have prolonged OS after debulking procedures. Surgery for patients who have responsive disease after TKIs treatment should be considered.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Tumores do Estroma Gastrointestinal/tratamento farmacológico
Tumores do Estroma Gastrointestinal/cirurgia
Cuidados Paliativos
Inibidores de Proteínas Quinases/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Intervalo Livre de Doença
Feminino
Seguimentos
Tumores do Estroma Gastrointestinal/mortalidade
Tumores do Estroma Gastrointestinal/patologia
Seres Humanos
Mesilato de Imatinib/uso terapêutico
Neoplasias Hepáticas/mortalidade
Neoplasias Hepáticas/secundário
Masculino
Meia-Idade
Neoplasias Peritoneais/mortalidade
Neoplasias Peritoneais/secundário
Proteínas Tirosina Quinases/antagonistas & inibidores
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 8A1O1M485B (Imatinib Mesylate); EC 2.7.10.1 (Protein-Tyrosine Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180227
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009097


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[PMID]:29424982
[Au] Autor:Fernández­Ruiz M; Cabezas­Palacios MN; Rodríguez­Zarco E; Tato­Varela S
[Ti] Título:[Gatrointestinal stromal tumor: a case report].
[Ti] Título:Tumor del estroma gastrointestinal: reporte de un caso..
[So] Source:Ginecol Obstet Mex;84(9):607-13, 2016 Sep.
[Is] ISSN:0300-9041
[Cp] País de publicação:Mexico
[La] Idioma:spa
[Ab] Resumo:Gastrointestinal stromal tumors are the most common mesenquimal neoplasms of the gastrointestinal tract. A preoperative diagnose of GIST it is very difficult to make, but up to 5% of the cases initially appear as a pelvic mass. Clinical case: 45-year-old patient attended in medical service by unspecific pain in the lower abdomen of several weeks of evolution. The abdominopelvic tomography evidence collection of 9×8 cm above of the uterus and sigma's right with air in the cavity, it is was compatible with pelvic abscess. Due to increased pain, we realized emergency exploratory laparotomy, which showed a 14 cm tumor, dependent of the small intestine, without ascites or involvement other organs of the digestive or reproductive tract. The excision of the tumor was successfully (non intraoperative rupture). The pathological study reported a bowel piece of 20 cm, in which a tumor of 14 cm with large central cavitation was identified. Histologically showed diffuse growth pattern and neoplastic epithelioid cells with low rate of mitosis (mitosis 1-2/5 mm2). The immunohistochemistry test reports strong expression of DOG-1 and focal expression in CD117 (c-kit), with very low proliferation index (Ki67). The molecular pathology study identified a mutation in exon 11, codon 557-558, the c-kit gene in the p.W557_K558del position. We use imatinib (400 mg/24 h) from the second month after surgery. Today keep in treatment, and clinical and laboratories following every month: in addition, to CT scans scheduled every 6 months.
[Mh] Termos MeSH primário: Dor Abdominal/etiologia
Neoplasias Gastrointestinais/diagnóstico
Tumores do Estroma Gastrointestinal/diagnóstico
[Mh] Termos MeSH secundário: Feminino
Neoplasias Gastrointestinais/patologia
Neoplasias Gastrointestinais/cirurgia
Tumores do Estroma Gastrointestinal/patologia
Tumores do Estroma Gastrointestinal/cirurgia
Seres Humanos
Mesilato de Imatinib/administração & dosagem
Laparotomia/métodos
Meia-Idade
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
8A1O1M485B (Imatinib Mesylate)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180210
[St] Status:MEDLINE


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[PMID]:29265184
[Au] Autor:Cony-Makhoul P; Gardembas M; Coiteux V; Carpentier N; Pommier C; Violet I; Quittet P; Berger MG; TARGET-RMC Investigators
[Ad] Endereço:Centre Hospitalier Annecy Genevois, Pringy, France.
[Ti] Título:Nilotinib after imatinib first-line: a real-life longitudinal cohort of patients with chronic myeloid leukaemia in chronic phase.
[So] Source:Br J Haematol;180(3):356-364, 2018 02.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This prospective, observational study enrolled 150 adult patients with chronic myeloid leukaemia (CML) in chronic phase (CP) treated with nilotinib as second-line after imatinib, in a real life setting in France. Two-thirds of patients switched to nilotinib treatment due to lack of imatinib efficacy. Of 146 evaluable patients, 16 (11·0%) (95% confidence interval: 6·4-17·2%) achieved uMR , defined as undetectable molecular disease in cDNA with MR sensitivity (≥10 000 ABL1 transcripts) at 18 months and confirmed at 24 months (primary endpoint). Among patients without major molecular response (MMR) or deep molecular response (DMR) at study entry, 66·3% achieved MMR and 44·2% DMR within a median of 5·7 and 6·24 months, respectively. Fifty-three patients (36·3%) have prematurely terminated the study before 24 months of follow-up, primarily due to nilotinib treatment discontinuation (n = 43; 29·5%), mainly motivated by treatment intolerance (n = 27; 18·5%) and inefficacy (n = 10; 6·8%). The most frequent extra-haematological adverse events (AEs) reported as related to treatment with nilotinib were pruritus (16·4%), asthenia (13·7%) and dry skin (13·0%). Ischaemic cardiovascular AEs were reported in 18 patients (12·3%). This French nationwide large cohort adds valuable information to the body of evidence on the efficiency and safety of nilotinib in the treatment of patients with CP-CML.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Leucemia Mieloide de Fase Crônica/tratamento farmacológico
Leucemia Mieloide de Fase Crônica/patologia
Inibidores de Proteínas Quinases/uso terapêutico
Pirimidinas/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/administração & dosagem
Antineoplásicos/efeitos adversos
Estudos de Coortes
Resistência a Medicamentos Antineoplásicos
Feminino
Proteínas de Fusão bcr-abl/genética
Seres Humanos
Mesilato de Imatinib/administração & dosagem
Mesilato de Imatinib/efeitos adversos
Mesilato de Imatinib/uso terapêutico
Leucemia Mieloide de Fase Crônica/genética
Leucemia Mieloide de Fase Crônica/mortalidade
Estudos Longitudinais
Masculino
Meia-Idade
Inibidores de Proteínas Quinases/administração & dosagem
Inibidores de Proteínas Quinases/efeitos adversos
Pirimidinas/administração & dosagem
Pirimidinas/efeitos adversos
Retratamento
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide); 0 (Antineoplastic Agents); 0 (BCR-ABL1 fusion protein, human); 0 (Protein Kinase Inhibitors); 0 (Pyrimidines); 8A1O1M485B (Imatinib Mesylate); EC 2.7.10.2 (Fusion Proteins, bcr-abl)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15042


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Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
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[PMID]:27771544
[Au] Autor:Miyamura K; Miyamoto T; Tanimoto M; Yamamoto K; Kimura S; Kawaguchi T; Matsumura I; Hata T; Tsurumi H; Saito S; Hino M; Tadokoro S; Meguro K; Hyodo H; Yamamoto M; Kubo K; Tsukada J; Kondo M; Aoki M; Okada H; Yanada M; Ohyashiki K; Taniwaki M
[Ad] Endereço:Department of Hematology, Japanese Red Cross Nagoya Daiichi Hospital, 3-35 Michisita-cho, Nakamura-ku, Nagoya 453-8511, Japan. Electronic address: miyamu@nagoya-1st.jrc.or.jp.
[Ti] Título:Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy.
[So] Source:Leuk Res;51:11-18, 2016 12.
[Is] ISSN:1873-5835
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. ClinicalTrials.gov: NCT01043874.
[Mh] Termos MeSH primário: Substituição de Medicamentos/métodos
Mesilato de Imatinib/administração & dosagem
Leucemia Mieloide de Fase Crônica/tratamento farmacológico
Polimorfismo Genético
Pirimidinas/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/uso terapêutico
Feminino
Seres Humanos
Leucemia Mieloide de Fase Crônica/genética
Masculino
Meia-Idade
Inibidores de Proteínas Quinases/uso terapêutico
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide); 0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 0 (Pyrimidines); 8A1O1M485B (Imatinib Mesylate)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


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Maia, Raquel Ciuvalschi
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[PMID]:27770655
[Au] Autor:da Cunha Vasconcelos F; Mauricio Scheiner MA; Moellman-Coelho A; Mencalha AL; Renault IZ; Rumjanek VM; Maia RC
[Ad] Endereço:Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenação de Pesquisa, Instituto Nacional de Câncer (INCA), RJ, Brazil.
[Ti] Título:Low ABCB1 and high OCT1 levels play a favorable role in the molecular response to imatinib in CML patients in the community clinical practice.
[So] Source:Leuk Res;51:3-10, 2016 12.
[Is] ISSN:1873-5835
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Despite the favorable clinical evolution of patients with chronic myeloid leukemia (CML), resistance or intolerance to imatinib is present in approximately 35% of patients. Sokal score is a widely used risk factor, however efflux and influx transporters are provisional risk factors implicated in imatinib resistance. This study analyzed Sokal score, ABCB1, ABCG2 and OCT1 mRNA transporter expression levels as well as P-glycoprotein expression and efflux transporters activity to seek a possible correlation between these factors and the molecular response at 12 months from imatinib start as well as 8-year overall survival (OS). Low plus intermediate Sokal score correlated to optimal imatinib responses, as well as OS at 8-years, thus confirming the established role of Sokal score as a prognostic factor in CML patients. Low ABCB1 and high OCT1 mRNA levels were associated with an optimal molecular response, while the inverse levels were associated with non-responders (warning and failure) patients. Our results suggest that ABCB1 and OCT1 mRNA expressions may present biological relevance to identify responder and non-responder patients to imatinib treatment.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Mesilato de Imatinib/uso terapêutico
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Transportador 1 de Cátions Orgânicos/genética
RNA Mensageiro/sangue
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/sangue
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/sangue
Adolescente
Adulto
Idoso
Resistência a Medicamentos Antineoplásicos
Feminino
Hospitais Comunitários
Seres Humanos
Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico
Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade
Masculino
Meia-Idade
Prognóstico
Indução de Remissão
Fatores de Risco
Taxa de Sobrevida
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCB1 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Antineoplastic Agents); 0 (Organic Cation Transporter 1); 0 (RNA, Messenger); 8A1O1M485B (Imatinib Mesylate)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


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[PMID]:28467002
[Au] Autor:Kayastha GK; Ranjitkar N; Gurung R; Kc RK; Karki S; Shrestha R; Rajbhandari P; Thapa RK; Poudyal B; Acharya P; Roberts DJ; Hayes B; Zimmerman M; Basnyat B
[Ad] Endereço:Patan Academy of Health Science, Patan Hospital, Kathmandu, Nepal.
[Ti] Título:The use of Imatinib resistance mutation analysis to direct therapy in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia patients failing Imatinib treatment, in Patan Hospital, Nepal.
[So] Source:Br J Haematol;177(6):1000-1007, 2017 06.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia (CML) can be successfully treated with Glivec (Imatinib), which is available free of cost through the Glivec International Patient Assistance programme (GIPAP) to patients with proven CML without means to pay for the drug. We review the acquired mutations in the tyrosine kinase encoded by the BCR-ABL1 gene underlying Glivec failure or resistance in a cohort of 388 imatinib-treated CML patients (149 Female and 239 male) registered between February 2003 and June 2016 in Nepal. Forty-five patients (11 female 34 male) were studied; 18 different BCR-ABL1 mutations were seen in 33 patients. P-loop mutation, Kinase domain and A-loop mutations were seen in 9, 16 and 4 patients respectively. Other mutations were seen in five patients. A T315I mutation was the most common mutation, followed by F359V and M244V. Sixteen mutations showed intermediate activity to complete resistance to Glivec. Among the 45 patients evaluated for BCR-ABL1 mutations, 4 were lost to follow-up, 14 died and 27 are still alive. Among the surviving patients, 16 are receiving Nilotinib, 5 Dasatinib and 3 Ponatinib, while 3 patients were referred to India, one of who received allogenic bone marrow transplantation. Understanding the spectrum of further acquired mutations in BCR-ABL1 may help to choose more specific targeted tyrosine kinase inhibitors that can be provided by GIPAP.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Resistência a Medicamentos Antineoplásicos/genética
Proteínas de Fusão bcr-abl/genética
Mesilato de Imatinib/uso terapêutico
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Mutação
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
Masculino
Proteínas Tirosina Quinases/genética
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (BCR-ABL1 fusion protein, human); 8A1O1M485B (Imatinib Mesylate); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.2 (Fusion Proteins, bcr-abl)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14683


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[PMID]:29310342
[Au] Autor:Zhang Z; Jiang T; Wang W; Piao D
[Ad] Endereço:Department of Colorectal Surgery, The First Affiliated Hospital of Harbin Medical University.
[Ti] Título:Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumor after failure with imatinib and sunitinib treatment: A meta-analysis.
[So] Source:Medicine (Baltimore);96(48):e8698, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: This meta-analysis aimed to evaluate the safety and efficacy of regorafenib as a treatment for patients with advanced (metastatic and/or unresectable) gastrointestinal stromal tumor (AGIST) after developing resistance to imatinib and sunitinib. METHODS: A literature search of databases such as PubMed, Embase, and Cochrane library was conducted up to February 2017. The pooled percentages and the corresponding 95% confidence intervals (CIs) were calculated using the Stata 11.0 software. RESULTS: Four studies involving 243 patients with AGIST were included. Results revealed that approximately 49% (95% CI 30-67), 14% (95% CI 5-23), and 41% (95% CI 21-61) of patients with AGIST showed clinical benefit (including complete response), partial response, and stable disease, respectively, after regorafenib treatment, which was given after failure with imatinib and sunitinib treatments. No complete response was found in the included studies. Pooled progression-free survival was 6.58 months (95% CI 4.62-8.54). Hypertension (20%; 95% CI 7-33), hand-foot skin reaction (22%; 95% CI 17-27), and hypophosphatemia (18%; 95% CI 5-41) were common grade ≥3 regorafenib-related adverse events in patients treated with regorafenib after failure with imatinib and sunitinib treatments. CONCLUSIONS: Forty-nine per cent of patients with AGIST benefited after regorafenib treatment after the development of resistance to imatinib and sunitinib. More studies should be performed to improve the clinical survival of patients with AGIST. Close monitoring and appropriate management of grade ≥3 regorafenib-related adverse events should be considered during treatment.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Resistência a Medicamentos Antineoplásicos
Tumores do Estroma Gastrointestinal/tratamento farmacológico
Compostos de Fenilureia/uso terapêutico
Piridinas/uso terapêutico
[Mh] Termos MeSH secundário: Tumores do Estroma Gastrointestinal/patologia
Seres Humanos
Mesilato de Imatinib/uso terapêutico
Indóis/uso terapêutico
Pirróis/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Indoles); 0 (Phenylurea Compounds); 0 (Pyridines); 0 (Pyrroles); 24T2A1DOYB (regorafenib); 8A1O1M485B (Imatinib Mesylate); V99T50803M (sunitinib)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180115
[Lr] Data última revisão:
180115
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008698


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[PMID]:29245294
[Au] Autor:Jung M; Park SH; Jeon YK; Won JK; Yang HK; Kim WH
[Ad] Endereço:aDepartment of PathologybDepartment of Surgery, Seoul National University HospitalcCancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
[Ti] Título:Gastrointestinal stromal tumor of unusual phenotype after imatinib treatment: A case report and diagnostic utility of ETV1 mRNA in situ hybridization.
[So] Source:Medicine (Baltimore);96(49):e9031, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Gastrointestinal stromal tumor (GIST) is the most common tumor of mesenchymal origin in gastrointestinal tract. Immunohistochemical (IHC) staining combined with a typical morphology is used for the diagnosis of GIST. Typically, IHC staining for v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene (KIT) and discovered on GIST-1(DOG1) is positive in almost all GISTs. However, imatinib mesylate, a specific inhibitor of KIT tyrosine kinase, frequently involves changes in the morphology and IHC staining of GIST, impeding the diagnosis. Recently, in situ hybridization (ISH) for E26 transformation-specific sequence variant 1 (ETV1) mRNA was introduced as a useful marker to diagnose GIST. PATIENT CONCERNS: We report 2 cases of gastric GIST, which expressed unusual phenotypes after imatinib therapy. DIAGNOSES: The first patient was found to have a gastric subepithelial tumor in gastroduodenoscopy done for regular checkup. In biopsy of the tumor, it showed homogenous spindle cells that were positive to standard IHC markers for GIST. The second patient visited our hospital because of a palpable mass in the abdomen. In abdominal computed tomography (CT), a tumor arising from the stomach was found. A needle biopsy was done and the patient was diagnosed of gastric GIST because the biopsy showed spindle cells positive to typical IHC markers for GIST. After imatinib treatment, in both patients, the resected tumors were composed of heterogeneous spindle cells negative to KIT, DOG1, and CD34 IHC staining, which was unusual for GIST. However, ISH for ETV1 mRNA done for both biopsied and resected tumors was positive, even after imatinib treatment. A molecular analysis found a mutation in exon 11 of KIT gene before and after imatinib therapy in both patients, confirming the diagnosis of GIST. INTERVENTIONS: Both patients took neoadjuvant imatinib treatment, and afterwards, underwent a surgical resection. OUTCOMES: The patients remain on imatinib treatment and no progression or recurrence has been detected to date. LESSONS: ISH for ETV1 mRNA is a useful technique in diagnosing GIST when IHC with KIT, DOG1, or CD34 fail to stain positive after imatinib therapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Proteínas de Ligação a DNA/genética
Tumores do Estroma Gastrointestinal/tratamento farmacológico
Mesilato de Imatinib/farmacologia
RNA Mensageiro/sangue
Neoplasias Gástricas/tratamento farmacológico
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Idoso
Biomarcadores Tumorais/genética
Éxons/genética
Feminino
Tumores do Estroma Gastrointestinal/diagnóstico
Tumores do Estroma Gastrointestinal/genética
Seres Humanos
Hibridização In Situ/métodos
Masculino
Mutação
Fenótipo
Proteínas Proto-Oncogênicas c-kit/efeitos dos fármacos
Neoplasias Gástricas/diagnóstico
Neoplasias Gástricas/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (DNA-Binding Proteins); 0 (ETV1 protein, human); 0 (RNA, Messenger); 0 (Transcription Factors); 8A1O1M485B (Imatinib Mesylate); EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009031


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[PMID]:27771813
[Au] Autor:Vale Rodrigues R; Santos F; Pereira da Silva J; Francisco I; Claro I; Albuquerque C; Lemos MM; Limbert M; Dias Pereira A
[Ad] Endereço:Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Rua Prof. Lima Basto, 1099-023, Lisbon, Portugal. rita.vale.rodrigues@gmail.com.
[Ti] Título:A case of multiple gastrointestinal stromal tumors caused by a germline KIT gene mutation (p.Leu576Pro).
[So] Source:Fam Cancer;16(2):267-270, 2017 04.
[Is] ISSN:1573-7292
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Multiple gastrointestinal stromal tumors (GISTs) caused by germline KIT gene mutations are an extremely rare autosomal dominant disorder. We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls. Somatic mutational analysis of the KIT gene revealed a substitution at codon 576 in exon 11 (p.Leu576Pro) in all tumors and normal ileal mucosa. The germline nature of this mutation was confirmed by mutation analysis in peripheral blood leukocytes. However, she had no familial history of GISTs and her parents did not carry the respective germline mutation.
[Mh] Termos MeSH primário: Neoplasias Gastrointestinais/genética
Tumores do Estroma Gastrointestinal/genética
Neoplasias Primárias Múltiplas/genética
Proteínas Proto-Oncogênicas c-kit/genética
Doenças Raras/genética
[Mh] Termos MeSH secundário: Adulto
Antineoplásicos/uso terapêutico
Astenia/etiologia
Biópsia
Análise Mutacional de DNA
Endoscopia Gastrointestinal
Éxons
Feminino
Hemorragia Gastrointestinal/etiologia
Neoplasias Gastrointestinais/complicações
Neoplasias Gastrointestinais/diagnóstico
Neoplasias Gastrointestinais/terapia
Tumores do Estroma Gastrointestinal/complicações
Tumores do Estroma Gastrointestinal/diagnóstico
Tumores do Estroma Gastrointestinal/terapia
Mutação em Linhagem Germinativa
Seres Humanos
Mesilato de Imatinib/uso terapêutico
Células Intersticiais de Cajal/patologia
Intestino Delgado/patologia
Intestino Delgado/cirurgia
Terapia Neoadjuvante
Neoplasias Primárias Múltiplas/complicações
Neoplasias Primárias Múltiplas/diagnóstico
Neoplasias Primárias Múltiplas/terapia
Estômago/patologia
Estômago/cirurgia
Tomografia Computadorizada por Raios X
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 8A1O1M485B (Imatinib Mesylate); EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171224
[Lr] Data última revisão:
171224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1007/s10689-016-9941-1



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