The prothrombotic state in cancer.

Neoplasms result from changes in the mechanisms of growth, differentiation, and cellular death. Cancers are of high clinical relevance due to their prevalence and associated morbidity and mortality. The clinical and biological diversity of cancer depends mainly on cellular origin and degree of differentiation. These changes result from alterations in molecular expression that generate a complex clinical, biochemical, and morphologic phenotype. Although cancer is associated with a hypercoagulable state, few cancers result in a thrombotic event. Many factors influence thrombotic incidence, such as advanced disease, central catheter placement, chemotherapy, neoplasia, and surgery. The pro-coagulant state is associated with anomalies in the vascular wall, blood flow, blood constituents (tissue factor, thrombin), coagulation state, and cell growth factors. Tumor cells perpetuate this phenomenon by releasing tissue factor, inflammatory cytokines, and growth factors. These changes favor cellular activation that gives rise to actions involving coagulation, inflammation, thrombosis, tumor growth, angiogenesis, and tumor metastases. These, in turn, are closely linked to treatment response, tumor aggressiveness, and host survival. Activation of the coagulation cascade is related to these phenomena through molecules that interact in these processes. As such, it is necessary to identify these mediators to facilitate treatment and improve outcomes.

New biomarkers in non-Hodgkin lymphoma and acute leukemias.

Biomarkers play a critical role in the medical care of patients with cancer, including in early detection of the disease, diagnostic accuracy, risk stratification, treatment, and follow-up. Biomarkers in hematological malignancies can support the redefinition of the diagnosis and adjustments in the treatment plan. Biomarkers can be classified into 4 categories: (1) protein antigens, (2) cytogenetic abnormalities, (3) genetic polymorphisms, and (4) gene expression. Efforts in genomics, proteomics, and metabolomics to observe new biomarkers that contribute to the development of clinical medicine with greater precision in the strategies that improve prevention, diagnosis, and treatment of patients with malignant hematological disease. New biomarkers should accomplish several issues such as the biological plausibility, methodology used, analytical validation, intellectual property registry, and legal framework of application. This knowledge should be transferred to health professionals who can carry out the process of its implementation in clinical practice.

[Response to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia]. / Respuesta a inhibidores de tirosina cinasa en pacientes con leucemia mieloide crónica.

BACKGROUND: Chronic myeloid leukemia represents 15 % of all the leukemias in adults. With the introduction of tyrosine kinase inhibitors, overall survival at 10 years is 80-90 %. The objective was to describe the epidemiology, complete cytogenetic response and major molecular response with tyrosine kinase inhibitors in patients with chronic myeloid leukemia. METHODS: It was performed a descriptive cross-sectional study of patients with chronic myeloid leukemia and Philadelphia chromosome-positive in treatment with tyrosine kinase inhibitors. RESULTS: The sample included 54 patients with a mean age of 41 years; 78 % of patients were in chronic phase, and in 8 % of patients were identified complex karyotype at diagnosis. All patients received imatinib as first-line treatment. We identified mutations in 8 %. The patients with primary or secondary resistance (30%) received second-generation tyrosine kinase inhibitors as a second-line therapy. Of 35 patients treated with imatinib, 23 had complete cytogenetic response, 23 had major molecular response, and 16 had loss of response to treatment. Of nine patients treated with nilotinib, two presented complete cytogenetic response, two major molecular response, and five loss of response to treatment. Of seven patients treated with dasatinib, two had complete cytogenetic response, two major molecular response, and four loss of response to treatment. CONCLUSIONS: Of patients studied, 30 % was resistant to imatinib, 52 % achieved a complete cytogenetic response, and 42 % major molecular response. The use of second generation tyrosine kinase inhibitors led to obtain a complete cytogenetic and major molecular response in fewer time.

INTRODUCCIÓN: la leucemia mieloide crónica representa 15 % de las leucemias en los adultos. Con los inhibidores de la tirosina cinasa, la sobrevida a 10 años es de 80 a 90 %. El objetivo de esta investigación fue describir las características epidemiológicas, respuesta citogenética completa y respuesta molecular mayor con inhibidores de tirosina cinasa en pacientes con leucemia mieloide crónica. MÉTODOS: se realizó un estudio transversal descriptivo de los expedientes clínicos de pacientes con leucemia mieloide crónica positivos a cromosoma Filadelfia que fueron sometidos a tratamiento con inhibidores de tirosina cinasa. RESULTADOS: se incluyeron 54 pacientes; la edad media fue de 41 años, 78 % estaba en fase crónica y en 8 % se detectaron cariotipos complejos al diagnóstico. Todos recibieron imatinib como tratamiento de primera línea. Se identificaron mutaciones en 8 % de los pacientes. Los pacientes con resistencia primaria o secundaria (30 %) recibieron inhibidores de tirosina cinasa de segunda generación como tratamiento de segunda línea. De 35 pacientes tratados con imatinib, 23 presentaron respuesta citogenética completa, 23 respuesta molecular mayor y 16, pérdida de respuesta. De nueve pacientes tratados con nilotinib, dos presentaron respuesta citogenética completa, dos respuesta molecular mayor y cinco, pérdida de respuesta. De siete pacientes tratados con dasatinib, dos presentaron respuesta citogenética completa, dos respuesta molecular mayor y cuatro, pérdida de respuesta. CONCLUSIONES: 30 % de los pacientes presentó resistencia, 52 % alcanzó una respuesta citogenética completa con imatinib y 42 % una respuesta molecular mayor. El uso de inhibidores de tirosina cinasa de segunda generación permite alcanzar respuestas citogenética completa y molecular mayor en menor tiempo.