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Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

TAMASHIRO, Mirian S.; AIKAWA, Nadia Emi; CAMPOS, Lucia Maria A.; CRISTOFANI, Lilian Maria; ODONE-FILHO, Vicente; SILVA, Clovis A.
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
96.49%
OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria) were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years). In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively). Likewise, the frequencies of anemia...

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

SCRIDELI, Carlos A.; ASSUMPCAO, Juliana G.; GANAZZA, Monica A.; ARAUJO, Marcela; TOLEDO, Silvia R.; LEE, Maria Lucia M.; DELBUONO, Elisabete; PETRILLI, Antonio S.; QUEIROZ, Rosane R.; BIONDI, Andrea; VIANA, Marcos B.; YUNES, Jose A.; BRANDALISE, Silvia R.
Fonte: FERRATA STORTI FOUNDATION Publicador: FERRATA STORTI FOUNDATION
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
96.49%
Background Minimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise. Design and Methods We analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements. Results At least one marker was detected by polymerase chain reaction in 96.4%, of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%,, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis...

mRNA Expression Profile of Multidrug Resistance Genes in Childhood Acute Lymphoblastic Leukemia. Low Expression Levels Associated With a Higher Risk of Toxic Death

CORTEZ, Maria A. A.; SCRIDELI, Carlos A.; YUNES, Jose A.; VALERA, Elvis T.; TOLEDO, Silvia R. C.; PAVONI-FERREIRA, Patricia C. B.; LEE, Maria L. M.; PETRILLI, Antonio S.; BRANDALISE, Silvia R.; TONE, Luiz G.
Fonte: WILEY-LISS Publicador: WILEY-LISS
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
96.39%
Background. Increased activity of multidrug resistance (MDR) genes has been associated with treatment failure in acute leukemias, although with controversial reports. The objective of the present study was to assess the expression profile of the genes related to MDR: ABCB1, ABCC1, ABCC3, ABCC2, and LRP/MVP in terms of the clinical and biological variable and the survival of children with acute lymphoblastic leukemia (ALL). Procedure. The levels of mRNA expression of the drug resistance genes ABCB1, ABCC1, ABCC3, ABCG2, and LRP/MVP were analyzed by quantitative real-time PCR using the median Values as cut-off points, in consecutive samples from 140 children with ALL at diagnosis. Results. Expression levels of the ABCG2 gene in the patient group as a whole (P=0.05) and of the ABCG2 and ABCC1 genes in patients classified as being at high risk were associated with higher rates of 5-year event-free survival (EFS) (P=0.04 and P=0.01). Expression levels of the ABCG2 gene below the median were associated with a greater chance of death related to treatment toxicity for the patient group as a whole (P=0.009) and expression levels below the median of the ABCG2 and ABCC1 genes were associated with a greater chance of death due to treatment toxicity for the high-risk group (P=0.02 and P=0.03...

IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase

Laranjeira, A. B. A.; Vasconcellos, J. F. de; Sodek, L.; Spago, M. C.; Fornazim, M. C.; Tone, L. G.; Brandalise, S. R.; Nowill, A. E.; Yunes, J. A.
Fonte: NATURE PUBLISHING GROUP; LONDON Publicador: NATURE PUBLISHING GROUP; LONDON
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
96.37%
The interaction of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells (BMSCs) has a positive impact on ALL resistance to chemotherapy. We investigated the modulation of a series of putative asparaginase-resistance/sensitivity genes in B-precursor ALL cells upon coculture with BMSCs. Coculture with stromal cells resulted in increased insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) expression by ALL cells. Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of recombinant rIGFBP7 (rIGFBP7) to the culture medium, showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase. In these assays, IGFBP7 function occurred mainly in an insulin-and stromal-dependent manner. ALL cells were found to contribute substantially to extracellular IGFBP7 levels in the conditioned coculture medium. Diagnostic BM plasma from children with ALL had higher levels of IGFBP7 than controls. IGFBP7, in an insulin/IGF-dependent manner, enhanced asparagine synthetase expression and asparagine secretion by BMSCs, thus providing a stromal-dependent mechanism by which IGFBP7 protects ALL cells against asparaginase in this coculture system. Importantly...

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP-EBMT analysis

Ruggeri, A.; Michel, G.; Dalle, J-H; Caniglia, M.; Locatelli, F.; Campos, A.; de Heredia, C. D.; Mohty, M.; Hurtado, J. M. P.; Bierings, M.; Bittencourt, H.; Mauad, M.; Purtill, D.; Cunha, R.; Kabbara, N.; Gluckman, E.; Labopin, M.; Peters, C.; Rocha, V.
Fonte: NATURE PUBLISHING GROUP; LONDON Publicador: NATURE PUBLISHING GROUP; LONDON
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
96.41%
To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR) = 0.4, P = 0.01) and for those transplanted in CR1 and CR2 (HR = 0.3, P = 0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P = 0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR = 2, P = 0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes. Leukemia (2012) 26...

Avaliação da força isocinética e efeitos de um programa de treinamento físico composto por exercícios de força alta intensidade e aeróbio de moderada intensidade em crianças e adolescentes com leucemia linfóide aguda; Isokinetic strength assessment and effects of an exercise training program comprising high-intensity resistance exercises and moderate-intensity aerobic exercises in children and adolescents with Acute Lymphoblastic Leukemia

Muratt, Mavi Diehl
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 26/05/2011 Português
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Introdução: o tratamento para leucemia aumentou a sobrevida de pacientes com leucemia aguda linfóide (LLA), mas a redução da força, a fadiga crônica e a qualidade de vida ainda são fatores de preocupação nessa população. Objetivo: comparar força isocinética em pacientes com LLA versus controles saudáveis. Além disso, investigar os efeitos de um programa de treinamento de força de alta intensidade combinado com exercício aeróbio de moderada intensidade em pacientes com LLA. Método: No intuito de responder aos objetivos distintos dessa dissertação, dois estudos sequênciais foram realizados. O primeiro deles trata-se de uma investigação transversal da força isocinética em pacientes com LLA versus controles saudáveis. Já o segundo teve como foco testar um programa de treinamento físico composto por exercícios intensos de força e aeróbios moderados por meio de um desenho prospectivo e longitudinal. No estudo 1, foram recrutados dez pacientes (grupo LLA) durante a fase de manutenção do tratamento de alto risco de LLA. Um grupo de dez crianças saudáveis, pareadas por idade, gênero, estatura e IMC foram selecionadas para o grupo controle (grupo CTRL). Para avaliar a força isocinética de membros inferiores e superiores...

Avaliação dos Efeitos Antineoplásicos da Zebularina em Linhagens Pediátricas de Leucemia Linfoide Aguda.; Evaluation of Antineoplastic Effects of Zebularine on Childhood Acute Lymphoblastic Leukemia Cell Lines.

Andrade, Augusto Faria
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 26/03/2012 Português
Relevância na Pesquisa
96.38%
A leucemia linfóide aguda (LLA) é a neoplasia hematológica mais comum na infância e representa uma doença heterogênea em relação à biologia e ao prognóstico e seu tratamento consiste principalmente em quimioterapia. Apesar dos avanços no tratamento, cerca de 20% dos pacientes apresentam recaída da doença e/ou óbito indicando a necessidade de terapias diferenciadas para esse grupo. Recentemente, drogas epigenéticas como inibidores de DNA metiltransferases (iDNMTs) tem mostrado efeitos anti-neoplásicos promissores para o tratamento de diversos tipos de neoplasias incluindo a LLA. Nos tumores, a hipermetilação gênica é encontrada em vários genes, incluindo genes de reparo do DNA, reguladores do ciclo celular e apoptose. Sendo assim, drogas desmetilantes estão sendo apontadas como promissores agentes para o tratamento do câncer. A Zebularina (ZB) é um iDNMT análogo de citidina que inibe a metilação do DNA. Esta droga tem mostrado resultados animadores para o tratamento de diversas neoplasias, incluindo glioblastoma, leucemia mielóide aguda, câncer de mama, próstata e outros. O objetivo deste trabalho foi avaliar os efeitos do tratamento com a ZB, associada ou não à quimioterápicos, em linhagens celulares pediátricas de LLA...

Oral manifestations during chemotherapy for acute lymphoblastic leukemia: A case report

Fernandes Gomes, Mônica; Rodrigues Kohlemann, Katya; Plens, Glauco; Silva, Marcelo Milone; Pontes, Elitânia Marinho; Da Rocha, João Carlos
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 307-313
Português
Relevância na Pesquisa
96.46%
A 14-year-old, male patient was referred for the treatment of mucositis, idiopathic facial asymmetry, and candidiasis. The patient had been undergoing chemotherapy for 5 years for acute lymphoblastic leukemia. He presented with a swollen face, fever, and generalized symptomatology in the mouth with burning. On physical examination, general signs of poor health, paleness, malnutrition, and jaundice were observed. The extraoral clinical examination showed edema on the right side of the face and cutaneous erythema. On intraoral clinical examination, generalized ulcers with extensive necrosis on the hard palate mucosa were observed, extending to the posterior region. Both free and attached gingivae were ulcerated and edematous with exudation and spontaneous bleeding, mainly in the superior and inferior anterior teeth region. The tongue had no papillae and was coated, due to poor oral hygiene. The patient also presented with carious white lesions and enamel hypoplasia, mouth opening limitation, and foul odor. After exfoliative cytology of the affected areas, the diagnosis was mixed infection by Candida albicans and bacteria. Recommended treatment was antibiotics and antifungal administration, periodontal prophylaxis, topical application of fluor 1.23%...

IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase

Laranjeira, A. B. A.; de Vasconcellos, J. F.; Sodek, L.; Spago, M. C.; Fornazim, M. C.; Tone, L. G.; Brandalise, S. R.; Nowill, A. E.; Yunes, J. A.
Fonte: Nature Publishing Group; London Publicador: Nature Publishing Group; London
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
96.37%
The interaction of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells (BMSCs) has a positive impact on ALL resistance to chemotherapy. We investigated the modulation of a series of putative asparaginase-resistance/sensitivity genes in B-precursor ALL cells upon coculture with BMSCs. Coculture with stromal cells resulted in increased insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) expression by ALL cells. Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of recombinant rIGFBP7 (rIGFBP7) to the culture medium, showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase. In these assays, IGFBP7 function occurred mainly in an insulin-and stromal-dependent manner. ALL cells were found to contribute substantially to extracellular IGFBP7 levels in the conditioned coculture medium. Diagnostic BM plasma from children with ALL had higher levels of IGFBP7 than controls. IGFBP7, in an insulin/IGF-dependent manner, enhanced asparagine synthetase expression and asparagine secretion by BMSCs, thus providing a stromal-dependent mechanism by which IGFBP7 protects ALL cells against asparaginase in this coculture system. Importantly...

Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

Mata,J.F.; Scrideli,C.A.; Queiroz,R.P.; Mori,B.O.; Emerenciano,M.; Pombo-de-Oliveira,M.S.; Tone,L.G.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2006 Português
Relevância na Pesquisa
96.37%
Infant acute lymphoblastic leukemia (IALL) is characterized by mixed lineage leukemia (MLL) gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C) to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of £0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively). Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion...

Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

Scrideli,Carlos Alberto; Defavery,Ricardo; Bernardes,José Eduardo; Tone,Luíz Gonzaga
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2001 Português
Relevância na Pesquisa
96.54%
CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH) for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%). There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%)...

Inactivation of the p15 gene in children with acute lymphoblastic leukemia

Cipolotti,Rosana; Lemos,José Alexandre Rodrigues; Defavery,Ricardo; Scrideli,Carlos Alberto; Dal Fabbro,Amaury Lellis; Tone,Luiz Gonzaga
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2003 Português
Relevância na Pesquisa
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CONTEXT: Tumor suppressor genes act on the control of cell cycle progression. In pediatric neoplasias, some of these genes may be considered to be markers for diagnosis or relapse, thus probably representing prognostic indicators. OBJECTIVE: To study the inactivation of the p15 gene in children with acute lymphoblastic leukemia. TYPE OF STUDY: Retrospective study. SETTING: Laboratory of Molecular Biology, Department of Pediatrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. PARTICIPANTS: Eighty-three children and adolescents with acute lymphoblastic leukemia were studied, with the examination of 83 bone marrow samples obtained at diagnosis, four obtained also during relapse, and two cerebrospinal fluid samples obtained from two cases of isolated relapse in the central nervous system. MAIN MEASUREMENTS: Homologous deletion of the p15 gene by multiplex polymerase chain reaction, and screening for point mutations by polymerase chain reaction/single-strand conformational polymorphism. RESULTS: Deletion of exon 2 of the p15 gene was observed in 15 children, including one case in which deletion was only verified during isolated central nervous system relapse. No case of exon 1 deletion, or that was suggestive of point mutations...

Acute lymphoblastic leukemia of childhood presenting as aplastic anemia: report of two cases

Villarreal-Martínez,Laura; Jaime-Pérez,José Carlos; Rodríguez-Martínez,Marisol; González-Llano,Oscar; Gómez-Almaguer,David
Fonte: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Publicador: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2012 Português
Relevância na Pesquisa
96.58%
Acute lymphoblastic leukemia is the most common malignancy in pediatric patients; its diagnosis is usually easy to establish as malignant lymphoblasts invade the bone marrow and peripheral blood. Some acute lymphoblastic leukemia patients may initially present with pancytopenia and a hypoplastic bone marrow leading to the initial diagnosis of aplastic anemia. In most of these patients clinical improvement occurs, with normalization of the complete blood count within six months, although recovery can also develop a few weeks after initiating steroid therapy. The etiologic relationship between the aplastic anemia features and the subsequent overt development of acute lymphoblastic leukemia has not been established. We describe the cases of two children who presented with severe infection and signs and symptoms of aplastic anemia confirmed by bone marrow aspirate and bone marrow biopsy that developed acute lymphoblastic leukemia thereafter. No specific therapy for aplastic anemia was administered, nevertheless a full spontaneous recovery was observed in both cases. Acute lymphoblastic leukemia was successfully treated with standard chemotherapy, both children remaining in complete remission 16 and 17 months after their initial aplastic anemia diagnosis.

Central nervous system involvement in acute lymphoblastic leukemia: diagnosis by immunophenotyping

Cancela,Camila Silva Peres; Murao,Mitiko; Souza,Marcelo Eduardo de Lima; Barcelos,José Márcio; Furtado,Vírginia Miguel; Silva,Maria Luiza; Viana,Marcos Borato; Oliveira,Benigna Maria de
Fonte: Sociedade Brasileira de Patologia Clínica; Sociedade Brasileira de Patologia; Sociedade Brasileira de Citopatologia Publicador: Sociedade Brasileira de Patologia Clínica; Sociedade Brasileira de Patologia; Sociedade Brasileira de Citopatologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2013 Português
Relevância na Pesquisa
96.42%
The central nervous system is the most commonly affected extramedullary site in acute lymphoblastic leukemia. Although morphologic evaluation of the cerebrospinal fluid has been traditionally used for diagnosing central nervous system involvement, it is a method of low sensitivity. The present study aimed at evaluating the use of immunophenotyping in the detection of blasts in the cerebrospinal fluid from children and adolescents with acute lymphoblastic leukemia.

Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

Tamashiro,Mirian S.; Aikawa,Nadia Emi; Campos,Lucia Maria A.; Cristofani,Lilian Maria; Odone-Filho,Vicente; Silva,Clovis A.
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2011 Português
Relevância na Pesquisa
96.49%
OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria) were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years). In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively). Likewise, the frequencies of anemia...

Effect of the Philadelphia chromosome on minimal residual disease in acute lymphoblastic leukemia

Brisco, M.; Sykes, P.; Dolman, G.; Neoh, S.; Hughes, E.; Peng, L.; Tauro, G.; Ekert, H.; Toogood, I.; Bradstock, K.; Morley, A.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //1997 Português
Relevância na Pesquisa
96.49%
The Philadelphia translocation is associated with a poor prognosis in adults and children with acute lymphoblastic leukemia, even though the majority of patients achieve remission. To test the hypothesis that the translocation leads to drug resistance in vivo, we studied 61 children and 20 adults with acute lymphoblastic leukemia and used the level of minimal residual disease at the end of induction as the measure of drug resistance in vivo. In children the presence of the translocation was associated with a significant increase in residual disease, indicating higher drug resistance in vivo; five of seven Philadelphia-positive children but only five of 54 Philadelphia-negative children had a minimal residual disease level >10-3, a level which is associated with a high risk of relapse in childhood acute lymphoblastic leukemia of standard risk. By contrast, in adults, residual disease and hence drug resistance was already higher than in children, and the presence of the Philadelphia translocation in seven patients had no obvious additional effect. We conclude that the Philadelphia chromosome may increase resistance to drugs in vivo in children, but not detectably in adults.; M J Brisco, P J Sykes, G Dolman, S-H Neoh, E Hughes, L-M Peng...

Garlic compounds selectively kill childhood pre-B acute lymphoblastic leukemia cells in vitro without reducing T-cell function: Potential therapeutic use in the treatmen of ALL

Hodge, G.; Davis, S.; Rice, M.; Tapp, H.; Saxon, B.; Revesz, T.
Fonte: Dove Medical Press Ltd Publicador: Dove Medical Press Ltd
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
Relevância na Pesquisa
96.39%
Drugs used for remission induction therapy for childhood precursor-B acute lymphoblastic leukemia (ALL) are nonselective for malignant cells. Several garlic compounds have been shown to induce apoptosis of cancer cells and to alter lymphocyte function. To investigate the effect of garlic on the apoptosis of ALL cells and lymphocyte immune function, cells from newly diagnosed childhood ALL patients were cultured with several commonly used chemotherapeutic agents and several garlic compounds. Apoptosis, lymphocyte proliferation and T-cell cytokine production were determined using multiparameter flow cytometry. At concentrations of garlic compounds that did not result in significant increases in Annexin V and 7-AAD staining of normal lymphocytes, there was a significant increase in apoptosis of ALL cells with no alteration of T-cell proliferation as determined by CD25/CD69 upregulation or interferonγ, interleukin-2 or tumor necrosis factor-α intracellular cytokine production. In contrast, the presence of chemotherapeutic agents resulted in nonselective increases in both lymphocyte and ALL apoptosis and a decrease in T-cell proliferation and cytokine production. In conclusion, we show selective apoptosis of malignant cells by garlic compounds that do not alter T-cell immune function and indicate the potential therapeutic benefit of garlic compounds in the treatment of childhood ALL.; http://www.dovepress.com/garlic-compounds-selectively-kill-childhood-pre-b-acute-lymphoblastic--peer-reviewed-article-BTT; Greg Hodge...

Untersuchungen zur Bedeutung aktivierender und inhibierender Rezeptoren auf Natürlichen Killerzellen bei deren zytotoxischen Aktivität gegenüber leukämischen Blasten der B-Zell-Reihe; Activating and inhibitory receptors on natural killer cells: analyses of their relevance for cytotoxic activity against blasts in B-lineage acute lymphoblastic leukemia

Bohlmann, Ulrike Barbara
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
96.37%
Natürliche Killerzellen (NK-Zellen) spielen eine wichtige Rolle bei der Immunabwehr maligne veränderter Körperzellen. Kindliche leukämische Blasten der B-Zell-Reihe sind häufig sehr resistent gegen die Lyse durch NK-Zellen. In dieser Arbeit wurde mithilfe von FACS-Analysen und Zytotoxizitätstests untersucht, welche Rolle verschiedene aktivierende und inhibierende Rezeptoren für die Erkennung und Elimination von Blasten bei der kindlichen akuten lymphatischen Leukämie der B-Zell-Reihe (B-Reihen-ALL) spielen. Eine neu entwickelte Auswertungsmethode ermöglichte eine differenziertere Auswertung von Qualitativen FACS-Analysen als übliche Auswertungsmethoden. Insgesamt wiesen die Ergebnisse darauf hin, dass kindliche B-Reihen-ALL-Blasten durch die Kombination aus geringer Expression von Liganden aktivierender NK-Zell-Rezeptoren und starker Expression von Liganden inhibierender NK-Zell-Rezeptoren sehr resistent gegen die Lyse durch NK-Zellen sind.; Natural killer cells (NK cells) play an important role in immune defense against human leukemia. In childhood B-lineage acute lymphoblastic leukemia (B-lineage ALL), blasts are often highly resistant to NK cell cytotoxicity. In this dissertation, the role of different activating and inhibitory receptors in the detection and elimination of blasts in childhood B-lineage ALL was analyzed using flow cytometry and cytotoxicity assays. A newly developed evaluation method allowed a more sophisticated evaluation of non-quantitative flow cytometry compared to common evaluation methods. The results of these analyses altogether indicated that blasts in childhood B-lineage ALL show a low expression of ligands for activating NK cell receptors and a high expression of ligands for inhibitory NK cell receptors. The combination of both seems to cause their high resistance to NK cell cytotoxicity.

Effects of a combined aerobic and strength training program in youth patients with acute lymphoblastic leukemia

Perondi, Maria Beatriz; Gualano, Bruno; Artioli, Guilherme Giannini; Painelli, Vitor de Salles; Odone Filho, Vicente; Netto, Gabrieli; Muratt, Mavi; Roschel, Hamilton; Pinto, Ana Lucia de Sa
Fonte: JOURNAL SPORTS SCIENCE & MEDICINE; BURSA Publicador: JOURNAL SPORTS SCIENCE & MEDICINE; BURSA
Tipo: Artigo de Revista Científica
Português
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96.42%
Cure rates of youth with Acute Lymphoblastic Leukemia (ALL) have increased in the past decades, but survivor's quality of life and physical fitness has become a growing concern. Although previous reports showed that resistance training is feasible and effective, we hypothesized that a more intense exercise program would also be feasible, but more beneficial than low- to moderate-intensity training programs. We aimed to examine the effects of an exercise program combining high-intensity resistance exercises and moderate-intensity aerobic exercises in young patients undergoing treatment for ALL. A quasi-experimental study was conducted. The patients (n = 6; 5-16 years of age) underwent a 12-week intra-hospital training program involving high-intensity strength exercises and aerobic exercise at 70% of the peak oxygen consumption. At baseline and after 12 weeks, we assessed sub-maximal strength (10 repetition-maximum), quality of life and possible adverse effects. A significant improvement was observed in the sub maximal strength for bench press (71%), lat pull down (50%), leg press (73%) and leg extension (64%) as a result of the training (p < 0.01). The parents' evaluations of their children's quality of life revealed an improvement in fatigue and general quality of life...

Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

Tamashiro, Mirian S.; Aikawa, Nadia Emi; Campos, Lucia Maria A.; Cristofani, Lilian Maria; Odone-Filho, Vicente; Silva, Clovis A.
Fonte: Universidade de São Paulo. Faculdade de Medicina Publicador: Universidade de São Paulo. Faculdade de Medicina
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; ; Formato: application/pdf
Publicado em 01/01/2011 Português
Relevância na Pesquisa
96.49%
OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria) were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years). In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively). Likewise, the frequencies of anemia...