RESUMO
BACKGROUND: Acute myeloid leukemia (AML) is the most common type of leukemia in adults. There are no previous studies evaluating AML treatment patterns in Puerto Rico. We describe the first-line therapy patterns and survival of patients diagnosed with AML in Puerto Rico using the Puerto Rico Central Cancer Registry Health Insurance Linkage Database (2011-2015). METHODS: We describe patient characteristics according to intensive, non-intensive, and non-treatment status. We used Cox proportional hazard models to evaluate the factors associated with the risk of death stratified by intensive and non-intensive therapy. For this study, 385 patients with AML were included. RESULTS: The mean age was 67 years old and 50.1% were female. Nearly half of AML patients (46.8%) received intensive treatment, 23.6% received non-intensive treatment, and 26.2% did not receive treatment. The overall 3-year survival rate was 17.9%. Among those who received intensive therapy, the risk of death among females was lower than males (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.44-0.93). Patients 60 years or older who received intensive treatment had a higher risk of death than younger patients (HR: 1.67, 95% CI: 1.09-2.55). Patients with poor/adverse risk receiving intensive (HR: 3.43, 95% CI: 1.76-6.69) or non-intensive (HR: 4.32, 95% CI: 1.66-11.28) treatment had a higher risk of death than patients with a favorable risk category. CONCLUSION: Our findings are the first step to monitor the quality of care of patients with AML in Puerto Rico, particularly related to the administration of appropriate induction therapies, which is one of the most important predictors of AML survival.
Assuntos
Quimioterapia de Indução , Leucemia Mieloide Aguda , Adulto , Idoso , Feminino , Hispânico ou Latino , Humanos , Seguro Saúde , Masculino , Porto Rico/epidemiologiaRESUMO
The bacterial enzyme asparaginase is the main treatment option for acute lymphoblastic leukemia. However, it causes side effects, such as immunological reactions, and presents undesirable glutaminase activity. As an alternative, we have been studying asparaginase II from Saccharomyces cerevisiae, coded by ASP3 gene, which was cloned and expressed in Pichia pastoris. The recombinant asparaginase (ASP) presented antileukemic activity and a glutaminase activity 100 times lower in comparison to its asparaginase activity. In this work, we describe the development of a delivery system for ASP via its covalent attachment to functionalized polyethylene glycol (PEG) polymer chains in the outer surface of liposomes (ASP-enzymosomes). This new delivery system demonstrated antiproliferative activity against K562 (chronic myeloid leukemia) and Jurkat (acute lymphocytic leukemia) cell lines similar to that of ASP. The antiproliferative response of the ASP-enzymosomes against the Jurkat cells suggests equivalence to that of the free Escherichia coli commercial asparaginase (Aginasa®). Moreover, the ASP-enzymosomes were stable at 4 °C with no significant loss of activity within 4 days and retained 82% activity up to 37 days. Therefore, ASP-enzymosomes are a promising antileukemic drug.
Assuntos
Antineoplásicos/química , Asparaginase/química , Leucemia/tratamento farmacológico , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Asparaginase/genética , Asparaginase/metabolismo , Asparaginase/farmacologia , Composição de Medicamentos/métodos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células Jurkat , Células K562 , Leucemia/patologia , Lipossomos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomycetales/genética , Saccharomycetales/metabolismo , Células Tumorais CultivadasRESUMO
Introducción: La leucemia promielocítica presenta particularidades biológicas y clínicas con respecto al resto de las leucemias mieloides agudas. El descubrimiento de los detalles moleculares de su patogénesis, posibilitó que su tratamiento, constituya una de las mejores representaciones de la investigación traslacional y esto hace que establezca un modelo para el desarrollo de terapias dirigidas a dianas moleculares con enfoque curativo en pacientes con cáncer. Objetivo: Abordar los principales avances en la terapia de la LPM desde el descubrimiento de los agentes diferenciadores hasta su estado actual. Métodos: Se realizó una búsqueda exhaustiva en bases de datos como Scielo, Pubmed, ScienceDirect, Redalyc y se utilizaron como referencias los artículos actualizados publicados principalmente en los últimos cinco años. Análisis y síntesis de la información: Se abordaron los principales avances en la terapia de este tipo de leucemia, desde el descubrimiento de los agentes diferenciadores hasta su estado actual, haciendo énfasis en su mecanismo de acción y nuevas opciones terapéuticas. Conclusiones: Los aportes realizados en el estudio etiopatogénico y molecular de la leucemia promielocítica y su impacto objetivo en la investigación clínica, constituyen uno de los mejores ejemplos de tratamiento dirigido a alteraciones moleculares específicas y representa un modelo de integración biológica, clínica y terapéutica en beneficio de los pacientes afectados con esta enfermedad(AU)
Introduction: Acute promyelocytic leukemia is a biologically and clinically different type from other acute myeloid leukemias. The discovery of molecular details in its pathogenesis enabled its treatment to constitute one of the best examples of translational research and makes a model for the development of targeted therapies with a curative approach in cancer patients. Objective: To analize the main advances in PML therapy from the discovery of differentiating agents to their current state. Methods: An exhaustive search was carried out in the databases as Scielo, Pubmed, ScienceDirect, Redalyc, and updated articles published mainly in the last five years were used as references. Analysis and synthesis of the information: The article addressed the main advances in the therapy of this type of leukemia, from the discovery of differentiating agents to its current state, emphasizing its mechanism of action and new therapeutic options. Conclusions: The contributions made in the etiopathogenic and molecular study of promyelocytic leukemia and its objective impact on clinical research constitute one of the best examples of treatment aimed at specific molecular alterations and represents a model of biological, clinical and therapeutic integration in benefit of patients affected with this disease(AU)
Assuntos
Humanos , Leucemia Promielocítica Aguda/terapia , Proteína SUMO-1 , Pesquisa Translacional BiomédicaRESUMO
Lasparaginase enzymes have been a vital component of acute lymphoblastic leukemia therapy for >40 years. Lasparaginase acts by depleting plasma Lasparagine, which is essential to the survival of leukemia cells. In contrast to normal cells, tumor cells cannot synthesize Lasparagine and thus depend on its external uptake for growth. Currently, three bacterial Lasparaginases are used in therapy; however, they are associated with severe sideeffects related to high toxicity and immunogenicity. The introduction of human Lasparaginaselike protein 1 in acute lymphoblastic leukemia treatment would avoid the problems caused by the bacterial enzymes; however, a major difficulty in the therapeutic use of the human enzyme comes from the fact that human Lasparaginase must be activated through an autoprocessing step, which is a lowefficiency process in vitro that results in reduced enzymatic activity. The present review article aimed to contribute to the understanding of the enzyme selfactivation process and focuses on the efforts made for the development of a therapeutic variant of human Lasparaginase.
Assuntos
Asparaginase/uso terapêutico , Autoantígenos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Ativação Enzimática , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
In acute myeloid leukemia (AML), mutations of the Fms-like tyrosine kinase 3 receptor (FLT3) and its overexpression are related with hyperleukocytosis, higher risk of relapse, and decrease of both disease-free survival and overall survival. It has been suggested that this phenomenon confers proliferative and survival advantages to the malignant blast cells. As a consequence, it is an attractive therapeutic target. As the best treatment strategy for mutated FLT3 AML remains to be defined, the addition of FLT3 inhibitor drugs to chemotherapy or to the bone marrow transplant approach has become a growing strategy. With encouraging results, this combination seems to be an attractive option. Relevant data regarding the current treatment trends on mutated FLT3 AML is reviewed here.
Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Terapia de Alvo Molecular , Tirosina Quinase 3 Semelhante a fms/genética , Proliferação de Células/efeitos dos fármacos , Intervalo Livre de Doença , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidoresRESUMO
ABSTRACT Adherence to imatinib mesylate improves clinical outcomes and promotes a reduction in health expenditure. However, treatment duration and lack of efficacy decrease adherence to pharmacotherapy, resulting in increased mortality associated with Chronic Myeloid Leukemia. This study aimed to evaluate and compare adherence and/or discontinuation of imatinib mesylate in different studies from the literature. An integrative review of original articles published between the years of 2004 and 2014 was performed using the databases PubMed/MEDLINE, Scopus and SciELO. The descriptor "imatinib" was used in two combinations employing the connector AND between terms: "medication adherence'' AND ''imatinib" AND "leukemia'' and ''patient compliance'' AND "imatinib" AND "leukemia". We identified 476 studies, being 14 included in the study. The rates of adherence and discontinuation were diverse, ranging from 19.0 to 97.0% and from 1.8 and 41.0%, respectively, and a high number of longitudinal studies was observed (71.4%). Most studies used questionnaires as an indirect method to assess adherence and factors related to poor adherence were adverse drug reactions, dose changes and unavailability of the medication. Patient education associated with follow up by pharmacists and other health professionals can improve patient adherence and minimize the pharmacotherapy discontinuation.