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1.
São Paulo; s.n; s.n; 2021. 84 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1380519

ABSTRACT

A enzima L-asparaginase de Escherichia coli (ASNase) é um biofármaco indicado para o tratamento de leucemia linfoblástica aguda, mas que pode causar reações de hipersensibilidade nos pacientes tratados. Na tentativa de amenizar esse efeito, foi desenvolvida a PEG-ASNase (enzima conjugada com polietilenoglicol) que apresenta a vantagem de ser menos imunogênica e ter maior meia-vida biológica. Mais recentemente, novas abordagens têm sido desenvolvidas visando aprimorar os processos de PEGuilação por meio de reações sítio dirigidas, por exemplo N-terminal, a fim de promover maior similaridade lote a lote e controle das características farmacocinéticas e farmacodinâmicas do biofármaco. Porém, existe ainda uma limitação associada à hidrólise do PEG reativo, desta forma surge a necessidade de procurar solventes alternativos para a PEGuilação que permitam manter a estabilidade das proteínas, aumentar o rendimento de PEGuilação e a estabilidade do PEG reativo. Nesse trabalho, líquidos iônicos foram investigados como solventes alternativos para a peguilação N-terminal de PEG-ASNase. Para tal, a estabilidade de ASNase em Lis foi investigada em LIs da família metil-imidazol, analisando a influência do aumento da cadeia alquílica e de diferentes ânions. A estabilidade da ASNase é favorecida quando em contato com Lis relativamente hidrofóbicos ([C2mim]Cl, [C4mim]Cl e [C6mim]Cl), mas sua a atividade é prejudicada quando o LI é muito polar, como o [C4mim][(CH3)2PO4] ou anfifílico como o [C12mim]Cl. Apesar de seu efeito desnaturante, o [C4mim][(CH3)2PO4] resultou no maior rendimento da reação de PEGuilação da ASNase (56%) quando empregado a 75% e a reação realizada em 10 min. O [C4mim]Cl resultou em rendimento semelhante ao tampão fosfato (~ 49%), mas ambos os LIs reduziram a poliPEGuilação. Portanto, os Lis [C4mim]Cl e [C4mim][(CH3)2PO4] fornecem uma alternativa viável à reação de PEGuilação pela redução na formação de espécies poliPEGuiladas, o que facilitaria os processos de purificação e permitiria maior controle lote a lote da reação, bem como pelo aumento do rendimento da reação no caso do [C4mim][(CH3)2PO4]


Escherichia coli L-asparaginase enzyme (ASNase) is a biopharmaceutical indicated for the treatment of acute lymphoblastic leukemia, but may cause hypersensitivity in the patients used. In an attempt to alleviate this effect, PEG-ASNase (polyethylene glycol conjugated enzyme) was developed, which has the advantage of being less immunogenic and having a longer biological half-life. More recently, new approaches have been applied to improve PEGylation processes through targeted sites, for example N-terminal, in order to promote greater similarity to the batch and control of the pharmacokinetic and pharmacodynamic characteristics of the biopharmaceutical. However, there is still a limitation associated with reactive PEG hydrolysis, thus increasing the need to look for alternative PEGylation solvents to maintain protein stability, increase PEGylation yield and use reactive PEG. In this work, ions were investigated as alternative solvents for the N-terminal PEG-ASNase. For example, a stability of ASNase in ILs was investigated in imidazole ILs by analyzing the influence of increased alkyl chain and different anions. ASNase stability is enhanced when in contact with relatively hydrophobic ILs ([C2min]Cl, [C4min]Cl and [C6min]Cl), but its activity is impaired when very polar ILs such as [C4min][(CH3)2PO4] or amphiphilic as [C12mim]Cl. Despite its denaturing effect, [C4min][(CH3)2PO4] resulted in higher yield of ASNase PEGylation reaction (56%) when employed at 75% and reaction performed in 10 min. [C4min]Cl yielded similar phosphate buffer yield (~ 49%), but both ILs reduced polyPEGylation. Therefore, [C4min]Cl and [C4min][(CH3)2PO4] Ils may use a viable alternative to the PEGylation reaction and reduce the formation of polyPEGylated species, or that facilitate purification processes and allow for greater batch use of the solution, as well as increased reaction yield in the case of [C4min][(CH3)2PO4]


Subject(s)
Ionic Liquids , Asparaginase/analysis , Escherichia coli/classification , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Protein Stability
2.
Braz. J. Pharm. Sci. (Online) ; 56: e18600, 2020. tab, graf
Article in English | LILACS | ID: biblio-1249141

ABSTRACT

To find the predictors of High Dose Methotrexate toxicities in childhood Acute Lymphoblastic Leukemia Patients. This study included 198 Childhood Acute Lymphoblastic Leukemia patients (303 infusions) who were treated with High Dose Methotrexate. Methotrexate levels at different time point were measured by modified enzyme multiplied immunoassay technique assay. The correlation between Methotrexate levels and toxicity was evaluated by Receiver Operating Characteristic curve. When the Methotrexate level at 42 h was lower than 0.76 µmol/L, the sensitivity for predicting thorough clearance at 66 h was 90.78%. When the Methotrexate level at 42 h was higher than1.5 µmol/L, the sensitivity for predicting delayed clearance was 82.17%. When the Methotrexate level at 66 h was higher than 0.5 µmol/L, the sensitivity for predicting Methotrexate toxicity was 89.09%. When the Methotrexate level at 66 h was lower than 0.1 µmol/L, the sensitivity for predicting Methotrexate nontoxicity was 92.73%. The Methotrexate level at 42 h could be predictor for delayed clearance. The Methotrexate level at 66 h could be predictor for toxicity.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Patients/classification , Methotrexate/administration & dosage , Methotrexate/analysis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Forecasting , ROC Curve , Enzyme Multiplied Immunoassay Technique/instrumentation , Dosage/adverse effects
3.
Arch. argent. pediatr ; 116(4): 500-507, ago. 2018. graf, tab
Article in English, Spanish | LILACS, BINACIS | ID: biblio-950042

ABSTRACT

Introducción: Los niños con síndrome de Down (SD) tienen mayor frecuencia de leucemia linfoblástica aguda (LLA) y menor supervivencia que pacientes sin síndrome de Down (NSD). Analizamos las características clínicas, demográficas-biológicas y respuestas al tratamiento en SD-LLA versus NSD-LLA. Pacientes y métodos: Pacientes (0-19 años) con LLA desde enero de 1990 a noviembre de 2016. Se compararon características demográficas biológicas y respuestas al tratamiento con chi cuadrado y Wilcoxon rank sum. La supervivencia global y el intervalo libre de eventos (ILE) se analizaron con Kaplan-Meier y el test log-rank. Resultados: Se incluyeron 1795 pacientes, 54 con SD. Los SD-LLA presentaron edad mayor (p= 0,0189). T odos inmuno fenotipo precursor-B, con menor incidencia de anomalías recurrentes (p < 0,0001). Demostraron mejor tasa de respuesta a prednisona (p= 0,09) y mayor mortalidad en inducción y remisión completa (p < 0,0001). Todas las muertes de los SD-LLA fueron relacionadas con el tratamiento. La sobrevida libre de eventos en niños SD-LLA vs.NSD-LLA fue 47 (± 8)% vs. 73 (± 1)% (p= 0,006) y el ILE de los SD-LLA vs. NSD-LLA fue 54 (± 9)% vs. 75 (± 1)% (p= 0,0297). La tasa de recaídas fue similar en ambos grupos (p= 0,6894). El ILE de los SD-LLA fue menor en el grupo de 6-9 años: 39 (± 19)% (p= 0,7885). Conclusiones: Los niños de 6-9 años con SD-LLA años presentó menor sobrevida. Aunque estos niños presentaron una mejor respuesta temprana, la sobrevida libre de eventos e ILE fueron menores debido a la mortalidad relacionada con el tratamiento.


Introduction. Children with Down syndrome (DS) more commonly have acute lymphoblastic leukemia (ALL) and a lower survival rate than those without Down syndrome (WDS). We analyzed the clinical, demographic, and biological characteristics and treatment response of children with DS-ALL versus those WDS-ALL. Patients and methods: Patients with ALL between January 1990 and November 2016. The demographic and biologic characteristics and treatment response were compared using the χ² and Wilcoxon rank-sum tests. The overall survival and event-free interval (EFI) were analyzed using the Kaplan-Meier and log-rank tests. Results. 1795 patients were included; 54 had DS. Patients with DS-ALL were older (p= 0.0189). All had B-cell precursor immunophenotype and a lower incidence of recurrent abnormalities (p < 0.0001). They showed a better response rate to prednisone (p= 0.09) and a higher mortality in induction and complete remission (p < 0.0001). All deaths of patients with DS-ALL were treatment-related. The event-free survival (EFS) was 47% (± 8%) versus 73% (± 1%) (p= 0.006) and the EFI was 54% (± 9%) versus 75% (± 1%) (p= 0.0297) among patients with DS-ALL versus those WDS-ALL, respectively. The rate of relapse was similar in both groups (p= 0.6894). The EFI of patients with DS-ALL was lower in the group aged 6-9 years: 39% (± 19%) (p= 0.7885). Conclusions. A lower survival was observed among children aged 6-9 years with DS-ALL. Although these children showed a better early response, their EFS and EFI were lower due to treatment-related mortality.


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Prednisone/administration & dosage , Down Syndrome/complications , Antineoplastic Agents, Hormonal/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Recurrence , Remission Induction , Survival Rate , Retrospective Studies , Age Factors , Statistics, Nonparametric , Disease-Free Survival , Kaplan-Meier Estimate , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
4.
Arch. argent. pediatr ; 116(4): 594-598, ago. 2018. ilus, tab
Article in Spanish | LILACS, BINACIS | ID: biblio-950049

ABSTRACT

La infección fúngica invasora ha aumentado en frecuencia a lo largo de la última década, y la sinusitis fúngica es cada vez más habitual. Los hongos del género Exserohilum (familia Pleosporaceae, orden Pleosporales) son filamentosos y dematiáceos, de localización ubicua. Se trata de patógenos emergentes, que producen, en la mayoría de los casos, infecciones sistémicas que afectan, principalmente, a los senos paranasales y los pulmones. Son más frecuentes en pacientes inmunosuprimidos, aunque pueden presentarse en pacientes inmunocompetentes. El tratamiento de estas infecciones comprende el tratamiento antifúngico, resección quirúrgica y restitución de la inmunidad. Se presenta el caso de una paciente con recaída medular de leucemia linfoblástica aguda con sinusitis fúngica invasiva por Exserohilum rostratum.


Invasive fungal infection has increased in frequency over the last decade, with fungal sinusitis becoming more frequent. The fungi of the genus Exserohilum (family Pleosporaceae, order Pleosporales) are filamentous and dematiaceous of ubiquitous location. It is an emerging pathogen, which in most cases produces a systemic infection that mainly affects the paranasal sinuses and lungs. It is more common in immunosuppressed patients, although it may occur in immunocompetent patients. The treatment is based on three pillars: antifungal treatment, surgical debridement and restitution of immunity. We present the case of a patient with medullary relapse of acute lymphoblastic leukemia with invasive fungal sinusitis by Exserohilum rostratum.


Subject(s)
Humans , Female , Child, Preschool , Ascomycota/isolation & purification , Sinusitis/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Invasive Fungal Infections/diagnosis , Recurrence , Sinusitis/microbiology , Sinusitis/therapy , Acute Disease , Debridement/methods , Invasive Fungal Infections/microbiology , Invasive Fungal Infections/therapy , Antifungal Agents/therapeutic use
5.
Bol. méd. Hosp. Infant. Méx ; 74(3): 227-232, May.-Jun. 2017. tab
Article in English | LILACS | ID: biblio-888620

ABSTRACT

Abstract: Acute lymphoblastic leukemia (ALL) affects the quality of life of many children in the world and particularly in Mexico, where a high incidence has been reported. With a proper financial investment and with well-organized institutions caring for those patients, together with solid platforms to perform high-throughput analyses, we propose the creation of a Mexican repository system of serum and cells from bone marrow and blood samples derived from tissues of pediatric patients with ALL diagnosis. This resource, in combination with omics technologies, particularly proteomics and metabolomics, would allow longitudinal studies, offering an opportunity to design and apply personalized ALL treatments. Importantly, it would accelerate the development of translational science and will lead us to further discoveries, including the identification of new biomarkers for the early detection of leukemia.


Resumen: La leucemia linfoblástica aguda (LLA) afecta la calidad de vida de una gran cantidad de individuos en edad pediátrica en todo el mundo; particularmente en México, donde se ha reportado una alta incidencia. Con un apropiado fondo de inversión financiera, así como instituciones adecuadamente organizadas al cuidado de los pacientes con LLA, en conjunto con plataformas sólidas para llevar a cabo análisis globales y de alto rendimiento, se propone la creación de un repositorio para la conservación de suero y células provenientes de médula ósea y sangre derivadas de pacientes pediátricos con LLA al diagnóstico. Estos recursos, en combinación con las tecnologías ómicas, en particular la proteómica y la metabolómica, podrían permitir el establecimiento de estudios longitudinales y ofrecer una oportunidad para el diseño y aplicación de tratamientos personalizados para la LLA. Esta estrategia permitiría acelerar el desarrollo de la ciencia traslacional, favoreciendo el hallazgo de importantes descubrimientos, incluyendo la identificación de nuevos biomarcadores para la detección temprana de la leucemia.


Subject(s)
Child , Humans , Biomarkers, Tumor/metabolism , Proteomics/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Metabolomics/methods , Quality of Life , Biological Specimen Banks , Early Diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precision Medicine/methods , Mexico
6.
Bol. méd. Hosp. Infant. Méx ; 74(1): 13-26, ene.-feb. 2017. tab, graf
Article in Spanish | LILACS | ID: biblio-888592

ABSTRACT

Resumen: En paralelo al proyecto de la secuenciación del genoma humano, se han desarrollado varias plataformas tecnológicas que están permitiendo ganar conocimiento sobre la estructura del genoma de las entidades humanas, así como evaluar su utilidad en el abordaje clínico del paciente. En la leucemia linfoblástica aguda (LLA), el cáncer infantil más común, las herramientas genómicas prometen ser útiles para detectar a los pacientes con alto riesgo de recaída, ya sea al diagnóstico o durante el tratamiento (enfermedad mínima residual), además de que permiten identificar los casos en riesgo de presentar reacciones adversas a los tratamientos antineoplásicos y ofrecer una medicina personalizada con esquemas terapéuticos diseñados a la medida del paciente. Un ejemplo claro de esto último es la identificación de polimorfismos de un solo nucleótido (SNPs) en el gen de la tiopurina metil transferasa (TPMT), donde la presencia de dos alelos nulos (homocigotos o heterocigotos compuestos) indica la necesidad de reducir la dosis de la mercaptopurina hasta en un 90% para evitar efectos tóxicos que pueden conducir a la muerte del paciente. En esta revisión se proporciona una visión global de la genómica de la LLA, describiendo algunas estrategias que contribuyen a la identificación de biomarcadores con potencial utilidad en la práctica clínica.


Abstract: In parallel to the human genome sequencing project, several technological platforms have been developed that let us gain insight into the genome structure of human entities, as well as evaluate their usefulness in the clinical approach of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, genomic tools promise to be useful to detect patients at high risk of relapse, either at diagnosis or during treatment (minimal residual disease), and they also increase the possibility to identify cases at risk of adverse reactions to chemotherapy. Therefore, the physician could offer patient-tailored therapeutic schemes. A clear example of the useful genomic tools is the identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl transferase (TPMT) gene, where the presence of two null alleles (homozygous or compound heterozygous) indicates the need to reduce the dose of mercaptopurine by up to 90% to avoid toxic effects which could lead to the death of the patient. In this review, we provide an overview of the genomic perspective of ALL, describing some strategies that contribute to the identification of biomarkers with potential clinical application.


Subject(s)
Child , Humans , Genomics/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Antimetabolites, Antineoplastic/administration & dosage , Recurrence , Biomarkers, Tumor/metabolism , Neoplasm, Residual/genetics , Polymorphism, Single Nucleotide , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Mercaptopurine/administration & dosage , Mercaptopurine/adverse effects , Methyltransferases/genetics , Antimetabolites, Antineoplastic/adverse effects
7.
Braz. j. med. biol. res ; 50(1): e5426, 2017. tab, graf
Article in English | LILACS | ID: biblio-839242

ABSTRACT

IGH gene rearrangement and IGK-Kde gene deletion can be used as molecular markers for the assessment of B lineage acute lymphoblastic leukemia (B-ALL). Minimal residual disease detected based on those markers is currently the most reliable prognosis factor in B-ALL. The aim of this study was to use clonal IGH/IGK-Kde gene rearrangements to confirm B-ALL diagnosis and to evaluate the treatment outcome of Tunisian leukemic patients by monitoring the minimal residual disease (MRD) after induction chemotherapy. Seventeen consecutive newly diagnosed B-ALL patients were investigated by multiplex PCR assay and real time quantitative PCR according to BIOMED 2 conditions. The vast majority of clonal VH-JH rearrangements included VH3 gene. For IGK deletion, clonal VK1f/6-Kde recombinations were mainly identified. These rearrangements were quantified to follow-up seven B-ALL after induction using patient-specific ASO. Four patients had an undetectable level of MRD with a sensitivity of up to 10-5. This molecular approach allowed identification of prognosis risk group and adequate therapeutic decision. The IGK-Kde and IGH gene rearrangements might be used for diagnosis and MRD monitoring of B-ALL, introduced for the first time in Tunisian laboratories.


Subject(s)
Humans , Male , Female , Child, Preschool , Adolescent , Middle Aged , Biomarkers, Tumor/genetics , Gene Rearrangement/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity
8.
Arq. bras. oftalmol ; 78(6): 382-384, Nov.-Dec. 2015. tab, graf
Article in English | LILACS | ID: lil-768178

ABSTRACT

ABSTRACT Acute lymphoblastic leukemia is a malignant hematopoietic neoplasia, which is rare in adults. Although ocular fundus alterations may be commonly observed in the course of the disease, such alterations are rarely the presenting signs of the disease. Here we describe the case of a patient with painless and progressive loss of visual acuity (right eye, 2/10; left eye, 3/10) developing over two weeks, accompanied by fever and cervical lymphadenopathy. Fundus examination showed bilateral macular serous detachment, which was confirmed by optical coherence tomography. Fluorescein angiography revealed hyperfluorescent pinpoints in the posterior poles. The limits of the macular detachment were revealed in the late phase of the angiogram. The results of blood count analysis triggered a thorough, systematic patient examination. The diagnosis of acute lymphoblastic leukemia B (CD10+) was established, and intensive systemic chemotherapy was immediately initiated. One year after the diagnosis, the patient remains in complete remission without any ophthalmologic alterations.


RESUMO A leucemia linfoblástica aguda é uma neoplasia maligna das células hematopoiéticas, incomum em adultos. Apesar da maioria dos casos apresentar alterações no fundo ocular no decurso da doença, estas são raramente forma de apresentação da mesma. Descreve-se o caso de uma doente com diminuição progressiva e indolor da acuidade visual (OD 2/10 e OE 3/10), que apresentava concomitantemente febre e adenopatias cervicais, com duas semanas de evolução. À oftalmoscopia apresentava descolamento seroso macular bilateral, confirmado por tomografia de coerência ótica. A angiografia fluoresceínica revelou pequenas lesões hiperfluorescentes tipo pinpoints no polo posterior. Nos tempos médios e tardios do exame adivinham-se os limites da bolsa do descolamento do neuroepitélio. As alterações encontradas no hemograma suscitaram um estudo sistêmico extenso. O diagnóstico de leucemia linfoblástica aguda B (CD10+) foi efetuado, iniciando-se, de imediato, quimioterapia sistêmica intensiva. Um ano após o diagnóstico a doente continua em remissão e sem alterações oftalmológicas de novo.


Subject(s)
Female , Humans , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Retinal Detachment/etiology , Fluorescein Angiography , Macula Lutea/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Retinal Detachment/drug therapy , Retinal Detachment/pathology , Tomography, Optical Coherence , Treatment Outcome , Visual Acuity
9.
Rev. latinoam. enferm. (Online) ; 23(4): 587-594, July-Aug. 2015. tab
Article in English | LILACS, BDENF | ID: lil-761693

ABSTRACT

AbstractObjective: to relate complaints presented by emergency room patients, classified using the Manchester Triage System, with the final outcome (discharge/death/transfer).Methods: prospective cohort study, involving 509 patients who were admitted to the emergency room and remained there for more than 24 hours after admission, being monitored to the final outcome. Data were analyzed with a statistical program using descriptive and analytical statistics.Results: the mean age of the patients was 59.1 years and 59.3% were male. The main complaints were unwell adult (130 - 22.5%), shortness of breath in adults (81 - 14.0%), abdominal pain in adults (58 - 10.0%) and behaving strangely (34 - 5.9%), with 87% of the patients being discharged. More deaths were found in the patients classified in the severe colors, with 42.8% classified as red, 17.0% as orange and 8.9% as yellow. Among the patients classified as green, 9.6% died.Conclusion: in the various colors of the Manchester Triage System, death prevailed in patients that presented the complaints of unwell adult, shortness of breath, head injury, major trauma, diarrhea and vomiting. The higher the clinical priority the greater the prevalence of death.


ResumoObjetivo:relacionar queixas apresentadas pelos pacientes classificados pelo Sistema de Triagem de Manchester em um pronto-socorro com o desfecho final (alta/óbito/transferência).Métodos:estudo de coorte prospectivo, realizado com 509 pacientes que deram entrada no pronto-socorro e que nele permaneceram por mais de 24 horas após a admissão, sendo acompanhados até o desfecho final. Os dados foram digitados e analisados com estatística descritiva e analítica em um pacote estatístico.Resultados:entre os pacientes, 59,3% eram do sexo masculino, com idade média de 59,1 anos. As queixas principais eram de mal-estar no adulto (130-22,5%), dispneia em adulto (81-14,0%), dor abdominal em adulto (58-10,0%), alterações de comportamento (34-5,9%), sendo que, desses, 87% recebeu alta. Foram encontrados mais óbitos nos pacientes classificados nas cores mais graves, sendo 42,8% classificados como vermelho, 17,0% laranja e 8,9% como amarelo. Entre os pacientes classificados como verde, 9,6% evoluiu para óbito.Conclusão:nas diversas cores do Sistema de Triagem Manchester, o óbito prevaleceu nos pacientes que apresentaram a queixa de mal-estar no adulto, dispneia, sofreram trauma craniano, trauma maior, diarreia e vômito. Quanto maior a prioridade clínica maior a prevalência de óbito.


ResumenObjetivo:relacionar las quejas presentadas por los pacientes clasificados por el Sistema de Clasificación de Manchester, en un servicio de urgencia, con el desenlace final (alta/muerte/ transferencia).Métodos:estudio de cohorte prospectiva, realizado con 509 pacientes que dieron entrada en el servicio de urgencia y que en él permanecieron por más de 24 horas después de la admisión, siendo seguidos hasta el desenlace final. Los datos fueron introducidos y analizados con estadística descriptiva y analítica, en un programa estadístico.Resultados:entre los pacientes, 59,3% eran del sexo masculino, con edad promedio de 59,1 años. Las quejas principales eran de malestar en adulto (130-22,5%), disnea en adulto (81-14,0%), dolor abdominal en adulto (58- 10,0%), alteraciones de comportamiento (34-5,9%), siendo que, de estos, 87% recibió alta. Fueron encontradas más muertes entre los pacientes clasificados con los colores más graves, siendo 42,8% clasificados como rojo, 17,0% naranja y 8,9% como amarillo. Entre los pacientes clasificados como verde, 9,6% evolucionó para la muerte.Conclusión:en los diversos colores del Sistema de Clasificación Manchester, la muerte prevaleció en los pacientes que presentaron la queja de malestar en adulto, disnea, sufrieron trauma craniano, trauma mayor, diarrea y vómito. Cuanto mayor es la prioridad clínica mayor es la prevalencia de la muerte.


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , HLA-B Antigens , Haplotypes/immunology , Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Tumor Necrosis Factor-alpha , Allografts , Disease-Free Survival , Graft vs Host Disease/genetics , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , HLA-B Antigens/genetics , HLA-B Antigens/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Siblings , Survival Rate , Tissue Donors , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
10.
J. pediatr. (Rio J.) ; 89(1): 64-69, jan.-fev. 2013. tab
Article in Portuguese | LILACS | ID: lil-668827

ABSTRACT

OBJETIVO: Analisar pacientes com menos de dois anos de idade com leucemia linfoblástica aguda atendidos no período de 1990 a 2010, em um centro de referência estadual. MÉTODOS: Estudo clínico, epidemiológico, transversal, descritivo e observacional. Pacientes incluídos tinham menos de dois anos de idade, com leucemia linfoblástica aguda, tratados no período de 1990 a 2010 na unidade de oncologia pediátrica de um centro de referência estadual, totalizando 41 casos. RESULTADOS: Todos os pacientes eram Caucasianos e 60,9% eram do sexo feminino. Com relação à idade, 24,38% tinham menos de seis meses, 17,07% tinham entre seis meses e um ano e 58,53% mais do que um ano de idade. A idade de seis meses foi estatisticamente significante para o desfecho de óbito. Os sinais e sintomas predominantes foram febre, hematomas e petéquias. Uma contagem de leucócitos superior a 100.000 foi observada em 34,14% dos casos; hemoglobina inferior a 11 em 95,13% e contagem de plaquetas inferior a 100.000, em 75,61% dos casos. Infiltração do sistema nervoso central estava presente em 12,91% dos pacientes. Em relação à linhagem, a linhagem B predominou (73%), mas a linhagem de células T foi estatisticamente significativa para o óbito. Trinta e nove por cento dos pacientes tiveram recorrência da doença. Em relação ao estado vital, 70,73% dos pacientes morreram, sendo choque séptico a principal causa. CONCLUSÕES: leucemia linfoblástica aguda em crianças tem uma alta taxa de mortalidade, principalmente em crianças menores de um ano e linhagem derivada de células T.


OBJECTIVE: To analyze patients younger than 2 years with acute lymphoblastic leukemia, treated in the period between 1990 and 2010 in a state reference center. METHODS: This was a clinical-epidemiological, cross-sectional, observational, and descriptive study. It included patients younger than 2 years with acute lymphoblastic leukemia, treated in the period of 1990 to 2010 in a pediatric oncology unit of a state reference center, totaling 41 cases. RESULTS: All patients were white ethnicity, and 60.9% were females. Regarding age, 24.38% were younger than 6 months, 17.07% were between 6 months and 1 year, and 58.53% were older than 1 year. The age of 6 months was statistically significant for the outcome of death. Predominant signs and symptoms were fever, bruising, and petechiae. A leukocyte count > 100,000 was found in 34.14% of cases, hemoglobin count < 11 in 95.13%, and platelet count < 100,000 in 75.61. Infiltration of central nervous system was present in 12.91% of patients. According to the lineage, B-cell lineage predominated (73%), but the T-cell line was statistically significant for death. 39% of patients had disease recurrence. In relation to vital status, 70.73% of the patients died; septic shock was the main cause. CONCLUSIONS: Acute lymphoblastic leukemia in infants has a high mortality rate, especially in children under 1 year and those with T-cell derived lineage.


Subject(s)
Female , Humans , Infant , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Age Distribution , Age of Onset , Brazil/epidemiology , Cross-Sectional Studies , Central Nervous System/pathology , Follow-Up Studies , Leukemic Infiltration , Leukocyte Count , Platelet Count , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Sex Factors , Shock, Septic/mortality
11.
Article in English | WPRIM | ID: wpr-148465

ABSTRACT

The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and to identify factors related to the decreased BMD in childhood cancer survivors. We studied 78 patients (34 boys, 44 girls) treated for childhood cancer. Twenty (25.7%) patients had lumbar BMD (LBMD) standard deviation score (SDS) lower than -2. Nineteen (24.4%) patients had femur neck BMD (FNBMD) SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17 +/- 1.39 vs -0.43 +/- 1.33, P = 0.025). The risk of having LBMD SDS < -2 was higher in the patients treated with glucocorticoid (GC) for graft-versus-host disease (GVHD) (36.6% vs 13.5%; odds ratio [OR], 3.7; P = 0.020). In multivariate logistic regression analysis, longer duration of GC treatment for GVHD (OR, 1.12; 95% confidence interval [CI], 1.05-1.20) and lower body mass index (BMI) SDS (OR, 0.59; 95% CI, 0.36-0.95) were associated with decreased LBMD SDS. These findings suggest that prolonged GC use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.


Subject(s)
Adolescent , Body Mass Index , Bone Density/drug effects , Bone Diseases, Metabolic/chemically induced , Child , Female , Glucocorticoids/adverse effects , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hormones/blood , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myeloid, Acute/pathology , Male , Osteoporosis/chemically induced , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Risk Factors , Survivors
12.
Braz. dent. j ; 23(6): 711-715, 2012. ilus, tab
Article in English | LILACS | ID: lil-662432

ABSTRACT

Despite high cure rates, approximately 20% of patients with acute lymphoblastic leukemia (ALL) have disease relapse. Isolated recurrence in oral cavity is extremely unusual. The aim of this paper is to report a case of an isolated relapse occurred in a child with T-lineage ALL. Clinical picture included swelling and pain in the right upper gingiva of the oral cavity, with no other clinical or hematological alterations. Diagnosis was confirmed by biopsy and immunohistochemical staining. Bone marrow aspiration was normal. Five months later leukemic infiltration of the bone marrow was detected and systemic chemotherapy was reintroduced. This case report highlights the relevance of dental care during and after chemotherapy, not only to treat lesions in the oral cavity resulting from the disease itself or from treatment side effects, but also to detect unusual sites of ALL relapse.


Apesar dos altos índices de cura, cerca de 20% dos pacientes com leucemia linfóide aguda (LLA) apresentam recidiva da doença. Recidiva isolada na cavidade oral é extremamente incomum. O objetivo deste trabalho é relatar um caso de recidiva isolada em criança com LLA de linhagem T. A apresentação clínica foi quadro de edema e dor na cavidade oral, na região superior da gengiva à direita, sem outras alterações clínicas ou hematológicas. O diagnóstico foi confirmado por meio de biópsia e imuno-histoquímica. O mielograma era normal. Cinco meses após a manifestação inicial na cavidade oral, foi detectada infiltração leucêmica na medula óssea. O tratamento com quimioterapia sistêmica foi reintroduzido. Este relato de caso ressalta a importância do acompanhamento clínico e odontológico durante e após o tratamento quimioterápico, não somente com o objetivo de tratar as alterações na cavidade oral decorrentes da própria doença ou dos efeitos adversos do tratamento, mas para que sejam detectadas apresentações incomuns de recidiva na LLA.


Subject(s)
Child, Preschool , Humans , Male , Gingival Neoplasms/diagnosis , Neoplasm Recurrence, Local/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Antineoplastic Agents/therapeutic use , Biopsy , Bone Marrow Examination , Dental Care for Chronically Ill , Diagnosis, Differential , Follow-Up Studies , Gingival Neoplasms/pathology , Immunohistochemistry , Leukemic Infiltration , Leukemia, T-Cell/diagnosis , Leukemia, T-Cell/pathology , Neoplasm Recurrence, Local/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Remission Induction
14.
Indian J Pediatr ; 2010 July; 77(7): 779-783
Article in English | IMSEAR | ID: sea-142629

ABSTRACT

Objective. To analyze the prognostic impact of overt testicular disease (OTD) at diagnosis and role of testicular irradiation in the same. Methods. Data of 579 boys treated at our center over 16 years was reviewed. Results. Fourteen (2.4%) males had OTD. 10 (71.4%) of these had high-risk disease. Patients with OTD, had a significantly higher incidence of mediastinal-adenopathy (p=0.001), hyperleucocytosis (p=0.004) and CNS disease at presentation (p<0.0001) compared to patients in continuous complete remission (CCR). 4 of the 11 patients with OTD, who opted for therapy, had relapse; 2 are in CCR. Although, survival in patients with OTD was inferior (p=0.183) compared to patients without OTD, it was not an independent prognostic factor (p=0.47). In the entire study cohort, symptom-diagnosis interval (p=0.006), white cell (p=0.001) and platelet count (p=0.001) at presentation were significantly associated with survival (Cox multivariate regression analysis). Conclusions. OTD was not an independent prognostic factor, despite association with high-risk features. Survival outcome was inferior. The observations indicate the need of revaluation of the present protocol with incorporation of intermediate dose and subsequently high-dose methotrexate (after assessment for toxicity and tolerance), risk-stratified therapy and plausibly omission of testicular irradiation.


Subject(s)
Adolescent , Antineoplastic Combined Chemotherapy Protocols , Child , Child, Preschool , Humans , Male , Methotrexate/administration & dosage , Multivariate Analysis , Neoplasm Recurrence, Local/prevention & control , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Analysis , Testicular Neoplasms/pathology , Testicular Neoplasms/radiotherapy
15.
Arch. venez. pueric. pediatr ; 73(2): 18-28, abr.-jun. 2010. tab, graf
Article in Spanish | LILACS | ID: lil-588883

ABSTRACT

La leucemia linfoblástica aguda (LLA) se caracteriza por la proliferación clonal y acumulación de células linfoides malignas en médula ósea y en sangre periférica. Identificar los aspectos clínico-hematológicos, evolución terapéutica y morbimortalidad en niños con LLA de novo tratados con el Protocolo Total XV modificado, en el Servicio de Hematología del Hospital Universitario de Caracas (HUC) entre 2003-2007. Estudio clínico-epidemiológico, descriptivo y retrospectivo mediante la revisión de historias clínicas de pacientes menores de18 años. Los síntomas clínicos al diagnóstico fueron hipertermia, astenia, cefalea, hiporexia, sangrado y dolor óseo; los signos: adenopatías, hepatoesplenomegalia y fiebre; mayor prevalencia en el género masculino: 64,7% y entre 1 a 10 años (67,7%). La mayoría presentó anemia, leucocitosis y trombocitopenia. La infiltración del SNC fue del 5,9%. Se obtuvo un 79,4% de remisión completa (RC)en la fase de inducción, la morbilidad principal fue por neutropenia febril y 8,7% de mortalidad. En la fase de consolidación, se mantuvo la tasa de RC (79,9%), la morbilidad fue por hepatotoxicidad y 6,8% de mortalidad. En la fase de mantenimiento, se mantuvo la tasa de RC 80% pero se presentó un 11,6% de recaídas, mayor morbilidad infecciosa y 19,2% de mortalidad. La sobrevida global (SG) y la sobrevida libre de enfermedad (SLE) con una mediana de seguimiento de 24 meses, fue: 57% y 18,8%, respectivamente. La estrategia para adaptar el Protocolo Total XV modificado en el Servicio de Hematología, no fue efectiva para mejorar la SG ni SLE al compararlo con la literatura internacional.


Acute lymphoblastic leukemia (ALL) is characterized by clonal proliferation and accumulation of malignant lymphoidcells in bone marrow and peripheral blood. To identify clinical and hematological aspects, therapeutic outcome and morbid mortality in children with de novo ALL treated with the modified Total Protocol XV, in the Department of Hematology, Hospital Universitario de Caracas (HUC) between 2003-2007. Clinical and epidemiological, descriptive, retrospective study by reviewing medical records of patients under 18 years. Clinical symptoms at diagnosis were hyperthermia, fatigue, headache, anorexia, bleeding and bone pain. Signs were lymphadenopathy, hepatosplenomegaly and fever, more prevalent in male 64.7% and in patients between 1 and 10 years (67.7 %). Mosthad anemia, leukocytosis and thrombocytopenia. CNS infiltration was present in 5.9%. We obtained a 79.4% complete remission (CR) in the induction phase, the major morbidity was febrile neutropenia and 8.7% mortality. In the consolidation phase, CR rate remained thesame (79.9%), morbidity was 6.8% for hepatotoxicity and mortality. In the maintenance phase, CR rate was 80% but there was an 11.6% relapse, and the infectious morbidity and mortality rate increased to 19.2%. Overall survival (OS) and disease-free survival (DFS) with a median follow-up of 24 months was 57% and 18.8% respectively. The strategy to adapt the Total Protocol XV modified in the Hematology Department was not effective in improving the OS and SLE when compared with international literature.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Hematopoietic Stem Cells/classification , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Child Care , Medical Records , Posology/pharmacology , Antineoplastic Combined Chemotherapy Protocols/standards
16.
Article in English | WPRIM | ID: wpr-72772

ABSTRACT

Breast metastases in cases leukemia are very rare and occur primarily in patients with acute myeloid leukemia. We report the involvement of breast metastases in a 30-year-old woman with acute T cell lymphoblastic leukemia. The patient's mammograms revealed an extremely dense pattern with ill-defined, denser mass-like lesions in both breasts. A bilateral breast ultrasonographic evaluation revealed lobular-shaped and partly ill-defined hypoechoic masses with a multi-septated nodular (mottled) appearance.


Subject(s)
Adult , Breast Neoplasms/drug therapy , Diagnosis, Differential , Female , Humans , Mammography , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Ultrasonography, Mammary
17.
IPMJ-Iraqi Postgraduate Medical Journal. 2008; 7 (4): 339-346
in English | IMEMR | ID: emr-108473

ABSTRACT

Despite the advances in treatment of acute lymphoblastic leukemia [ALL], CNS relapse remains an obstacle to successful treatment. This study was performed to determine the frequency of CNS relapse in ALL patients and to study risk factors and outcome after CNS relapse. A retrospective study done on 364 patients diagnosed as ALL in Central Teaching Hospital for Children-Baghdad for the period from 1[st] Jan 2000 to 31[st] Mar 2005. ALL patients whom diagnosed after 1[st] Jan 2004 received CTHC 2004 protocol .The following parameters were studied: gender, age, hepatomegaly, splenomegaly, LAP, mediastinal mass, initial WBC count, platelets count, FAB morphology, initial CNS involvement and if the patient received radiotherapy. 35 patients were excluded from the study. Out of 329 eligible patients, 76 patients [23.1%] had CNS relapse [isolated or combined], with mean duration before CNS relapse 12.30 +/- 8.28 months and median of 11 months. The following factors were significantly associated with development of CNS relapse: male gender, age <2 years, massive hepatomegaly, massive splenomegaly, lymphadenopathy, mediastinal mass, initial WBC count >/= 50000/mm, initial CNS involvement, and patients who did not receive prophylactic CNS radiation. The study shows that frequency of CNS relapse decreased significantly after addition of three intrathecal doses during induction]. Shorter duration between diagnosis of ALL and CNS relapse was associated with higher mortality. Frequency of CNS relapse and mortality rate still higher than globally-accepted figures. Intensification of systemic and CNS-directed therapy, significantly decreased these figures in our patients


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Central Nervous System/pathology , Prognosis , Retrospective Studies , Risk Factors
18.
Indian J Pathol Microbiol ; 2007 Jan; 50(1): 78-81
Article in English | IMSEAR | ID: sea-73853

ABSTRACT

OBJECTIVES: To study the pattern of chromosomal abnormalities in adult patients with acute lymphoblastic leukemia. STUDY DESIGN: A retrospective study. Place and duration of study: January 1998 to June 2005 at the Cytogenetics department, Aga Khan University Hospital, Karachi. PATIENTS AND METHODS: A retrospective analysis of cytogenetic studies was carried out in patients who were diagnosed as ALL and were more than 15 years of age. Cytogenetic analysis was performed using a trypsin-Giemsa banding technique. Karyotypes were interpreted using International System for Cytogenetics Nomenclature (1995) criteria. RESULTS: The requests were received for cytogenetic analysis of bone marrow specimens in 69 patients who were diagnosed as ALL. Cytogenetic results were available in 62 patients; out of which 51 were males and 11 were females. 44 patients (70%) were found to have a normal karyotype. In 18 patients (29%), abnormal karyotype was found. CONCLUSION: Cytogenetic studies should be part of the initial work up of every patient with ALL. Larger scale studies will help refine our understanding of the less common chromosomal patterns and conduct multivariate analysis to define the relative prognostic value of karyotypic results.


Subject(s)
Adolescent , Adult , Chromosome Aberrations/classification , Chromosome Banding , Cytogenetic Analysis , Female , Humans , Karyotyping , Male , Pakistan , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Retrospective Studies
19.
Rev. colomb. cancerol ; 10(4): 291-294, dic. 2006. ilus, tab
Article in Spanish | LILACS | ID: lil-484492

ABSTRACT

Se analizó la historia clínica de un paciente con diagnóstico de leucemia linfoide aguda atendido en el Instituto Nacional de Cancerología entre 1989 y 2000. En el artículo se describe la leucemia linfoblástica aguda (LLA) como la enfermedad neoplásica más frecuente en los niños y se realiza un breve recorrido a través de la evolución histórica de esta patología.Se resalta la importancia de la morfología en el diagnóstico oportuno de dicho paciente y la necesidad de continuar con la valoración morfológica, en conjunto con las técnicas inmunológicas, citoquímicas y genéticas. Esto facilita el diagnóstico y el tratamiento, lo cual permite obtener un mejor pronóstico de esta enfermedad.


Subject(s)
Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Medical Records
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