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[PMID]:29288428
[Au] Autor:Scappaticci GB; Marini BL; Nachar VR; Uebel JR; Vulaj V; Crouch A; Bixby DL; Talpaz M; Perissinotti AJ
[Ad] Endereço:Department of Pharmacy Services and Clinical Sciences, Michigan Medicine and University of Michigan College of Pharmacy, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, USA.
[Ti] Título:Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG.
[So] Source:Ann Hematol;97(4):573-584, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000-45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.
[Mh] Termos MeSH primário: Nucleotídeos de Adenina/uso terapêutico
Envelhecimento
Antimetabólitos Antineoplásicos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Arabinonucleosídeos/uso terapêutico
Quimioterapia de Indução
Leucemia Mieloide Aguda/tratamento farmacológico
Vidarabina/análogos & derivados
[Mh] Termos MeSH secundário: Nucleotídeos de Adenina/efeitos adversos
Nucleotídeos de Adenina/economia
Idoso
Idoso de 80 Anos ou mais
Antimetabólitos Antineoplásicos/efeitos adversos
Antimetabólitos Antineoplásicos/economia
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Protocolos de Quimioterapia Combinada Antineoplásica/economia
Arabinonucleosídeos/efeitos adversos
Arabinonucleosídeos/economia
Estudos de Casos e Controles
Doença Hepática Induzida por Substâncias e Drogas/economia
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia
Doença Hepática Induzida por Substâncias e Drogas/mortalidade
Doença Hepática Induzida por Substâncias e Drogas/terapia
Estudos de Coortes
Terapia Combinada/economia
Redução de Custos
Custos e Análise de Custo
Citarabina/efeitos adversos
Citarabina/economia
Citarabina/uso terapêutico
Fator Estimulador de Colônias de Granulócitos/efeitos adversos
Fator Estimulador de Colônias de Granulócitos/economia
Fator Estimulador de Colônias de Granulócitos/uso terapêutico
Custos Hospitalares
Seres Humanos
Incidência
Quimioterapia de Indução/efeitos adversos
Quimioterapia de Indução/economia
Tempo de Internação
Leucemia Mieloide Aguda/economia
Leucemia Mieloide Aguda/mortalidade
Michigan/epidemiologia
Meia-Idade
Neutropenia/induzido quimicamente
Neutropenia/economia
Neutropenia/mortalidade
Neutropenia/terapia
Pontuação de Propensão
Estudos Retrospectivos
Análise de Sobrevida
Centros de Atenção Terciária
Vidarabina/efeitos adversos
Vidarabina/economia
Vidarabina/uso terapêutico
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenine Nucleotides); 0 (Antimetabolites, Antineoplastic); 0 (Arabinonucleosides); 04079A1RDZ (Cytarabine); 143011-72-7 (Granulocyte Colony-Stimulating Factor); 762RDY0Y2H (clofarabine); FA2DM6879K (Vidarabine)
[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:171231
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3217-1


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[PMID]:29395041
[Au] Autor:Bertrand A; Favier B; Devaux Y; Goy F; Marcault-Derouard A; Veyet V; Cervos M; Schell M
[Ad] Endereço:Centre Léon-Bérard, hospitalisation à domicile pédiatrique, IHOPe, 1, place du Pr-J.-Renaut, 69373 Lyon cedex 08, France. Electronic address: amandine.bertrand@ihope.fr.
[Ti] Título:[Intravenous chemotherapy at home: A pediatric monocentric experience].
[Ti] Título:Chimiothérapie intraveineuse à domicile en cancérologie pédiatrique : une expérience monocentrique..
[So] Source:Bull Cancer;105(2):155-161, 2018 Feb.
[Is] ISSN:1769-6917
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:INTRODUCTION: Our home care unit (HCU) developed the administration of IV chemotherapy at home for some pediatric oncologic patients. METHODS: We conducted a retrospective monocentric analysis, leading to identify patients with at least one sequence of chemotherapy at home in 2015. RESULTS: Two hundred and forty four sequences of home chemotherapy have been administered in 2015. We identified two situations for home IV chemotherapy. Pediatric oncologist of day hospital prescribes the sequence. The chemotherapy is delivered at hospital for the first day. HCU takes over for the next days at home. For a sequence replacing a conventional hospitalization, the attending physician examines the patient, and confirm the clinical validation. The pediatric oncologist of HCU checks lab exams, and prescribes the chemotherapy. For both situations, IV chemotherapy is prepared by our hospital pharmacy, delivers at home or at day hospital, and HCU team manages home material and organizes hospitalization. CONCLUSIONS: This kind of organization allows setting up home IV CT for more and more patients. It allows to limit daily hospitalization for some patients living far from the hospital, and whose therapies lead to several hospitalizations.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Serviços Hospitalares de Assistência Domiciliar/organização & administração
Neoplasias/tratamento farmacológico
[Mh] Termos MeSH secundário: Antineoplásicos/uso terapêutico
Criança
Citarabina/administração & dosagem
Neoplasias Oculares/tratamento farmacológico
Feminino
Glioma/tratamento farmacológico
Acesso aos Serviços de Saúde
Neoplasias Hematológicas/tratamento farmacológico
Seres Humanos
Injeções Intravenosas/estatística & dados numéricos
Masculino
Enfermagem Oncológica
Enfermagem Pediátrica
Pediatras
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Estudos Retrospectivos
Fatores de Tempo
Vimblastina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 04079A1RDZ (Cytarabine); 5V9KLZ54CY (Vinblastine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180204
[St] Status:MEDLINE


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[PMID]:29381943
[Au] Autor:Xu X; Liang G; Duan M; Zhang L
[Ad] Endereço:Department of Anesthesiology.
[Ti] Título:Acute myeloid leukemia presenting as erythema nodosum: A case report.
[So] Source:Medicine (Baltimore);96(47):e8666, 2017 Nov.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Erythema nodosum (EN), a type of septal panniculitis, could be a rare nonspecific cutaneous presentation of acute myeloid leukemia (AML). PATIENT CONCERNS: A 58-year-old Chinese female was admitted for a 4-week history of painful cutaneous lesions, accompanied by a sternal pain and fever. The lesions once resolved spontaneously but then recurred. Physical examination revealed warm, tender, indurated, rounded, erythematous to violaceous nodules in bilateral lower extremities, ranging in diameter from 1 to 6 cm. Blood marrow examination was compatible with AML-M2. DIAGNOSES: AML-M2 presenting as EN. INTERVENTIONS: Daunorubicin and cytarabine were used in induction chemotherapy. The patient achieved complete remission and her skin lesions disappeared simultaneously. Six courses of consolidation chemotherapy were conducted in the following 6 months. OUTCOMES: The patient died due to AML relapse. LESSONS: The case strengthens the awareness of cutaneous involvement of AML and raises oncological vigilance in patients with EN.
[Mh] Termos MeSH primário: Citarabina/administração & dosagem
Daunorrubicina/administração & dosagem
Eritema Nodoso
Leucemia Mieloide Aguda
[Mh] Termos MeSH secundário: Antineoplásicos/administração & dosagem
Exame de Medula Óssea/métodos
Eritema Nodoso/diagnóstico
Eritema Nodoso/etiologia
Evolução Fatal
Feminino
Seres Humanos
Quimioterapia de Indução/métodos
Leucemia Mieloide Aguda/complicações
Leucemia Mieloide Aguda/diagnóstico
Leucemia Mieloide Aguda/fisiopatologia
Meia-Idade
Recidiva
Indução de Remissão/métodos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 04079A1RDZ (Cytarabine); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008666


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[PMID]:29369169
[Au] Autor:Dong R; Ji J; Liu H; Wang J; He X
[Ad] Endereço:Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine.
[Ti] Título:Primary spinal mucosa-associated lymphoid tissue lymphoma: A case report.
[So] Source:Medicine (Baltimore);97(4):e9329, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent B-cell lymphoma which occurs mainly in the organs having mucosal layer and owns a fairly good prognosis. To date, 7 cases of spinal primary MALT has been reported before. However, there is no consensus on the optimal adjuvant treatment modalities for primary spinal MALT. The aim of this study was to add a new case of MALT which responded well to systemic therapy to the literature and to review the current literature. PATIENT CONCERNS: A 68-year-old woman visited to our hospital due to back pain and progressive bilateral lower extremity weakness for 2 months. Magnetic resonance imaging (MRI) of the spine revealed a diffusely contrast-enhancing epidural mass extending from vertebral body T6 to T8 with compression of the spinal cord. Due to the spinal cord compression, patient underwent surgical resection. Histological examination indicated monocytoid small B-cells. Immunochemical study demonstrates that most tumor cells were positive for CD20, CD21, CD45, CD79a, CD43, bcl-2 with Ki-67 labing index was 15%, but were negative for CD3, CD5 cyclin D1, BCL6, and CD23. The positron emission tomography/computer tomography (PET/CT) revealed that right iliac wing and right liver were metastases for the standard uptake value (SUV) were 9.05 and 8.35, respectively. DIAGNOSES: Based on these findings, final diagnosis of spinal MALT lymphoma was made. INTERVENTIONS: After the diagnosis, the patient received 6 cycles of immuno-chemotherapy and repeated intrathecal methotrexate and intrathecal cytarabine. OUTCOMES: At 1 year follow up, no recurrence or other dissemination was detected. LESSONS: Chemotherapy and/or radiation have been employed in larger case series. While there is no defined treatment guideline for this rare disease entity, our reported case suggests a favorable prognosis when combining both surgical and adjuvant systemic approach.
[Mh] Termos MeSH primário: Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
Neoplasias da Coluna Vertebral/diagnóstico por imagem
[Mh] Termos MeSH secundário: Idoso
Antineoplásicos/uso terapêutico
Citarabina/uso terapêutico
Feminino
Seres Humanos
Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico
Linfoma de Zona Marginal Tipo Células B/patologia
Metotrexato/uso terapêutico
Neoplasias da Coluna Vertebral/tratamento farmacológico
Neoplasias da Coluna Vertebral/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 04079A1RDZ (Cytarabine); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009329


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[PMID]:29262503
[Au] Autor:Wang Y; Han ZX; Zhang JC
[Ad] Endereço:Department of Oncology, Xuzhou Central Hospital of Southeast University, Xuzhou 221000, China.
[Ti] Título:[Effects of bone marrow stromal cells on the chemotherapeutic sensitivity of acute lymphoblastic leukemia cells].
[So] Source:Zhonghua Zhong Liu Za Zhi;39(12):885-890, 2017 Dec 23.
[Is] ISSN:0253-3766
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the influences of bone marrow stromal cells, components of extracellular matrix and cytokine secreted by stromal cells on the chemotherapeutic sensitivity of acute lymphoblastic leukemia cells to cytosine arabinoside (Ara-C). The co-culture model of acute lymphoblastic leukemia cell Sup-B15 and bone marrow stromal cell OP9 was constructed. Sup-B15 cells were cultured alone or co-cultured with OP9 cells, inactivated OP9 cells, the conditional medium (CM) of co-cultured OP9 cells and Sup-B15 cells, the CM of OP9 cells alone or Sup-B15 cells alone, respectively. The effects of different concentrations of Ara-C on the proliferation of each Sup-B1 cell group mentioned above were detected by cell counting kit-8 (CCK-8) method. The effects of different concentrations of Ara-C on the apoptosis of each group were detected by flow cytometry (FCM). The expressions of Bcl-2 protein in each group were detected by western blot. The results of CCK-8 test showed that the inhibitory efficiency of Ara-C was in a dose-dependent manner. With different concentrations of Ara-C treatment for 48 hours, the half maximal inhibitory concentrations (IC(50)) of Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group were 0.510 and 0.339 µg/ml, respectively, significantly higher than 0.091 µg/ml of Sup-B15 cultured alone group ( <0.05). The IC(50) of CM of Sup-B15 and OP9 co-cultured group was 0.204 µg/ml, significantly higher than 0.087 µg/ml of the CM of OP9 cultured alone group ( <0.05) and 0.097 µg/ml of the CM of Sup-B15 cultured alone group ( <0.05). The results of flow cytometry showed that with 0.10 µg/ml Ara-C treatment for 24 hours, the early apoptotic cell percentages of Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group and Sup-B15 cultured alone group were (6.67±2.19) %, (8.95±3.04) % and (20.46±2.63) %, respectively. The early apoptotic cell percentages of Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group were significantly lower than that of Sup-B15 cultured alone group ( <0.05). The early apoptotic cell percentages of the CM of Sup-B15 and OP9 co-cultured group, the CM of OP9 cultured alone group and the CM of Sup-B15 cultured alone group were (11.16±2.97)%, (22.08±2.71)% and (19.25±1.57)%, respectively, the former two of which were significantly lower than the last one ( <0.05). The results of western blot showed that the relative expression levels of Bcl-2 protein of Sup-B15 cultured alone group, Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group, the CM of Sup-B15 and OP9 co-cultured group, the CM of OP9 cultured alone group and the CM of Sup-B15 cultured alone group were 1.00±0.00, 1.53±0.03, 1.38±0.01, 1.26±0.05, 1.03±0.01 and 0.98±0.02, respectively. The expression levels of bcl-2 protein of three combined groups were significantly higher than that of Sup-B15 cultured alone group ( <0.05). while no statistically significant difference was observed between the CM of OP9 cultured alone group and the CM of Sup-B15 cultured alone group ( >0.05). Bone marrow stromal cell OP9, the components of bone marrow extracellular matrix and cytokine secreted by stromal cells are involved in the induction of the chemotherapeutic resistance of Sup-B15 cells to Ara-C.
[Mh] Termos MeSH primário: Antimetabólitos Antineoplásicos/farmacologia
Células da Medula Óssea/secreção
Citarabina/farmacologia
Citocinas/fisiologia
Citocinas/secreção
Resistência a Medicamentos Antineoplásicos
Células Mesenquimais Estromais/secreção
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
[Mh] Termos MeSH secundário: Apoptose
Contagem de Células
Linhagem Celular Tumoral
Técnicas de Cocultura
Meios de Cultivo Condicionados
Seres Humanos
Proteínas Proto-Oncogênicas c-bcl-2
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (BCL2 protein, human); 0 (Culture Media, Conditioned); 0 (Cytokines); 0 (Proto-Oncogene Proteins c-bcl-2); 04079A1RDZ (Cytarabine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0253-3766.2017.12.002


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[PMID]:29209924
[Au] Autor:Oosten LEM; Chamuleau MED; Thielen FW; de Wreede LC; Siemes C; Doorduijn JK; Smeekes OS; Kersten MJ; Hardi L; Baars JW; Demandt AMP; Stevens WBC; Nijland M; van Imhoff GW; Brouwer R; Uyl-de Groot CA; Kluin PM; de Jong D; Veelken H
[Ad] Endereço:Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. l.e.m.oosten@lumc.nl.
[Ti] Título:Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of four treatment regimens.
[So] Source:Ann Hematol;97(2):255-266, 2018 Feb.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linfoma de Burkitt/tratamento farmacológico
Análise Custo-Benefício
Infecções por HIV/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Linfoma de Burkitt/complicações
Linfoma de Burkitt/economia
Linfoma de Burkitt/mortalidade
Carmustina/economia
Carmustina/uso terapêutico
Ciclofosfamida/economia
Ciclofosfamida/uso terapêutico
Citarabina/economia
Citarabina/uso terapêutico
Etoposídeo/economia
Etoposídeo/uso terapêutico
Feminino
Infecções por HIV/complicações
Infecções por HIV/economia
Infecções por HIV/mortalidade
Seres Humanos
Ifosfamida/economia
Ifosfamida/uso terapêutico
Masculino
Melfalan/economia
Melfalan/uso terapêutico
Metotrexato/economia
Metotrexato/uso terapêutico
Meia-Idade
Estadiamento de Neoplasias
Estudos Retrospectivos
Rituximab/economia
Rituximab/uso terapêutico
Análise de Sobrevida
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Nm] Nome de substância:
04079A1RDZ (Cytarabine); 4F4X42SYQ6 (Rituximab); 6PLQ3CP4P3 (Etoposide); 8N3DW7272P (Cyclophosphamide); Q41OR9510P (Melphalan); U68WG3173Y (Carmustine); UM20QQM95Y (Ifosfamide); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180123
[Lr] Data última revisão:
180123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3167-7


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[PMID]:29200162
[Au] Autor:Valliyammai N; Nancy NK; Sagar TG; Rajkumar T
[Ad] Endereço:Departments of Molecular Oncology.
[Ti] Título:Study of NOTCH1 and FBXW7 Mutations and Its Prognostic Significance in South Indian T-Cell Acute Lymphoblastic Leukemia.
[So] Source:J Pediatr Hematol Oncol;40(1):e1-e8, 2018 Jan.
[Is] ISSN:1536-3678
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:NOTCH1/FBXW7 mutations trigger oncogenic NOTCH1 signaling and its downstream target genes play crucial roles in the molecular pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). In the present study, NOTCH1 and FBXW7 mutations were studied in 25 primary T-ALL samples. All 34 exons of NOTCH1 and hotspot exons (exon 9 and exon 10) of FBXW7 were polymerase chain reaction amplified and sequenced for mutations. Our results showed that 13/25 (52%) were NOTCH1-mutated, of which 11 patients (44%) showed mutation in the hotspot exons. Four patients (16%) had mutations in non-hotspot exons of NOTCH1. Notably, 2 T-ALL patients (8%) harbored mutations in both hotspot and non-hotspot exons of NOTCH1, whereas 2 patients (8%) had mutations in the hotspot exons of FBXW7. In all, 7 mutations were identified which were not previously reported. The real-time polymerase chain reaction study in 15 patients revealed that increased expression of activated NOTCH1 was found in NOTCH1/FBXW7 hotspot exon-mutated cases. In addition, NOTCH1/FBXW7-mutated patients had showed upregulated HES1, c-MYC, NOTCH3 gene expression. When survival analysis was performed including samples (n=50) from our previous study, an early treatment response and better survival was observed in NOTCH1/FBXW7 hotspot-mutated patients. Our study suggests that NOTCH1/FBXW7 hotspot-mutated T-ALL cases had better response to ALL BFM-95 protocol.
[Mh] Termos MeSH primário: Proteína 7 com Repetições F-Box-WD/genética
Mutação
Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética
Prognóstico
Receptor Notch1/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Protocolos de Quimioterapia Combinada Antineoplásica
Asparaginase
Criança
Pré-Escolar
Ciclofosfamida
Citarabina
Análise Mutacional de DNA
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Índia/epidemiologia
Lactente
Recém-Nascido
Masculino
Mercaptopurina
Metotrexato
Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico
Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia
Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade
Prednisona
Análise de Sobrevida
Vincristina
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (F-Box-WD Repeat-Containing Protein 7); 0 (FBXW7 protein, human); 0 (NOTCH1 protein, human); 0 (Receptor, Notch1); 04079A1RDZ (Cytarabine); 5J49Q6B70F (Vincristine); 8N3DW7272P (Cyclophosphamide); E7WED276I5 (Mercaptopurine); EC 3.5.1.1 (Asparaginase); VB0R961HZT (Prednisone); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.1097/MPH.0000000000001006


  8 / 13803 MEDLINE  
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[PMID]:29189507
[Au] Autor:Felix A; Leblanc T; Petit A; Nelkem B; Bertrand Y; Gandemer V; Sirvent A; Paillard C; Schmitt C; Rohrlich PS; Fenneteau O; Ragu C; Michel G; Auvrignon A; Baruchel A; Leverger G
[Ad] Endereço:Department of Pediatric Hematology and Oncology, Trousseau Hospital.
[Ti] Título:Acute Myeloid Leukemia With Central Nervous System Involvement in Children: Experience From the French Protocol Analysis ELAM02.
[So] Source:J Pediatr Hematol Oncol;40(1):43-47, 2018 Jan.
[Is] ISSN:1536-3678
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Central nervous system (CNS) involvement at diagnosis of pediatric acute myeloid leukemia (AML) is not considered as an independent prognostic factor. This study describes the prognostic value of pediatric AML with CNS involvement at diagnosis. Pediatric patients were treated for de novo AML in the French multicenter trial ELAM02. Lumbar puncture was carried out in the first week, and the treatment was adapted to the CNS status. No patient received CNS radiotherapy. The patients were classified into 2 groups: CNS+ and CNS-. Of the 438 patients, 16% (n=70) had CNS involvement at diagnosis, and 29% showed clinical signs. The patients with CNS disease were younger (40% were below 2 y old), had a higher white blood cell count (median of 45 vs. 13 G/L), and had M4 and M5 morphologies. The complete remission rate was similar at 92.8% for CNS+ and 88.5% for CNS-. There was no significant difference between the CNS+ and the CNS- group in overall survival (76% and 71%, respectively) and event-free survival (57% and 52%, respectively). Regarding the occurrence of first relapse, the CNS+ group had a higher combined relapse rate of 26.1% compared with 10% for the CNS- group. The results indicate that CNS involvement at diagnosis of pediatric AML is not an independent prognostic factor. Triple intrathecal chemotherapy combined with high-dose intravenous cytarabine should be the first-line treatment for CNS disease.
[Mh] Termos MeSH primário: Neoplasias do Sistema Nervoso Central/diagnóstico
Leucemia Mieloide Aguda/diagnóstico
Prognóstico
[Mh] Termos MeSH secundário: Adolescente
Fatores Etários
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Estudos de Casos e Controles
Neoplasias do Sistema Nervoso Central/tratamento farmacológico
Neoplasias do Sistema Nervoso Central/mortalidade
Criança
Pré-Escolar
Citarabina/administração & dosagem
França
Seres Humanos
Lactente
Leucemia Monocítica Aguda
Leucemia Mieloide Aguda/tratamento farmacológico
Leucemia Mieloide Aguda/mortalidade
Leucemia Mielomonocítica Aguda
Contagem de Leucócitos
Recidiva
Análise de Sobrevida
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
04079A1RDZ (Cytarabine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1097/MPH.0000000000001034


  9 / 13803 MEDLINE  
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[PMID]:29111347
[Au] Autor:De Cola A; Franceschini M; Di Matteo A; Colotti G; Celani R; Clemente E; Ippoliti R; Cimini AM; Dhez AC; Vallée B; Raineri F; Cascone I; Destouches D; De Laurenzi V; Courty J; Federici L
[Ad] Endereço:Dipartimento di Scienze Mediche, Orali e Biotecnologiche, CESI-MeT, Centro Scienze dell'Invecchiamento e Medicina Traslazionale, Universita' "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
[Ti] Título:N6L pseudopeptide interferes with nucleophosmin protein-protein interactions and sensitizes leukemic cells to chemotherapy.
[So] Source:Cancer Lett;412:272-282, 2018 Jan 01.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:NPM1 is a multifunctional nucleolar protein implicated in several processes such as ribosome maturation and export, DNA damage response and apoptotic response to stress stimuli. The NPM1 gene is involved in human tumorigenesis and is found mutated in one third of acute myeloid leukemia patients, leading to the aberrant cytoplasmic localization of NPM1. Recent studies indicated that the N6L multivalent pseudopeptide, a synthetic ligand of cell-surface nucleolin, is also able to bind NPM1 with high affinity. N6L inhibits cell growth with different mechanisms and represents a good candidate as a novel anticancer drug for a number of malignancies of different histological origin. In this study we investigated whether N6L treatment could drive antitumor effect in acute myeloid leukemia cell lines. We found that N6L binds NPM1 at the N-terminal domain, co-localizes with cytoplasmic, mutated NPM1, and interferes with its protein-protein associations. N6L toxicity appears to be p53 dependent but interestingly, the leukemic cell line harbouring the mutated form of NPM1 is more resistant to treatment, suggesting that NPM1 cytoplasmic delocalization confers protection from p53 activation. Moreover, we show that N6L sensitizes AML cells to doxorubicin and cytarabine treatment. These studies suggest that N6L may be a promising option in combination therapies for acute myeloid leukemia treatment.
[Mh] Termos MeSH primário: Leucemia Mieloide Aguda/tratamento farmacológico
Proteínas Nucleares/fisiologia
Peptídeos/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Citarabina/farmacologia
Doxorrubicina/farmacologia
Seres Humanos
Mutação
Proteínas Nucleares/análise
Proteínas Nucleares/genética
Proteína Supressora de Tumor p53/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N6L peptide); 0 (Nuclear Proteins); 0 (Peptides); 0 (Tumor Suppressor Protein p53); 04079A1RDZ (Cytarabine); 117896-08-9 (nucleophosmin); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171205
[Lr] Data última revisão:
171205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171108
[St] Status:MEDLINE


  10 / 13803 MEDLINE  
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[PMID]:28457008
[Au] Autor:Coltro G; Mannelli F; Guglielmelli P; Pacilli A; Bosi A; Vannucchi AM
[Ad] Endereço:CRIMM, Centro di Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
[Ti] Título:A life-threatening ruxolitinib discontinuation syndrome.
[So] Source:Am J Hematol;92(8):833-838, 2017 08.
[Is] ISSN:1096-8652
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Inibidores de Proteínas Quinases/efeitos adversos
Pirazóis/efeitos adversos
Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente
Síndrome de Abstinência a Substâncias/etiologia
Trombocitemia Essencial/tratamento farmacológico
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Terapia Combinada
Citarabina/administração & dosagem
Diagnóstico Diferencial
Progressão da Doença
Relação Dose-Resposta a Droga
Feminino
Transplante de Células-Tronco Hematopoéticas
Seres Humanos
Idarubicina/administração & dosagem
Janus Quinase 2/antagonistas & inibidores
Janus Quinase 2/genética
Leucemia Mieloide Aguda/etiologia
Leucemia Mieloide Aguda/terapia
Meia-Idade
Pneumonia/diagnóstico
Inibidores de Proteínas Quinases/administração & dosagem
Inibidores de Proteínas Quinases/farmacologia
Inibidores de Proteínas Quinases/uso terapêutico
Embolia Pulmonar/diagnóstico
Pirazóis/administração & dosagem
Pirazóis/farmacologia
Pirazóis/uso terapêutico
Indução de Remissão
Síndrome do Desconforto Respiratório do Adulto/diagnóstico
Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem
Síndrome do Desconforto Respiratório do Adulto/terapia
Síndrome de Abstinência a Substâncias/terapia
Trombocitemia Essencial/genética
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (INCB018424); 0 (Protein Kinase Inhibitors); 0 (Pyrazoles); 04079A1RDZ (Cytarabine); EC 2.7.10.2 (JAK2 protein, human); EC 2.7.10.2 (Janus Kinase 2); ZRP63D75JW (Idarubicin)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171204
[Lr] Data última revisão:
171204
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1002/ajh.24775



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