RESUMEN
Cytotoxic agents like Hydroxyurea, Busulfan and Interferon-alpha are to date the most commonly used therapeutic approaches in Essential Thrombocythemia (ET). However, few data on the efficacy and safety of these agents in the long-term are currently available. We report a retrospective analysis of the long-term outcome of 386 consecutive ET patients, followed at single Institution for a median follow-up of 9.5 years (range, 3-28.5). Cytoreductive therapy was administered to 338 patients (88%), obtaining a response in 86% of cases. Forty-five patients (12%) experienced a thrombosis. Among baseline characteristics, only history of vascular events prior to ET diagnosis predicted a higher incidence of thrombosis. Evolution in acute leukemia/myelofibrosis occurred in 6 (1,5%) and 20 (5%) patients, and was significantly higher in patients receiving sequential cytotoxic agents. Overall survival was 38% at 19 years and was poorer for patients older than 60 years, with higher leukocytes count (>15 x 10(9)/L), hypertension and mellitus diabetes at ET diagnosis and for patients experiencing a thrombotic event during follow-up. Cytoreductive therapy was effective in decreasing platelet number with negligible toxicity; however, thrombocytosis control did not reduce the incidence of thrombosis and, for patients who received sequential therapies, the probability of disease evolution was higher and survival was poorer.
Asunto(s)
Citostáticos/efectos adversos , Trombocitemia Esencial/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Citostáticos/administración & dosificación , Citostáticos/uso terapéutico , Diabetes Mellitus/epidemiología , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hemorragia/inducido químicamente , Humanos , Hipertensión/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , Análisis de Supervivencia , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/mortalidad , Trombofilia/tratamiento farmacológico , Trombofilia/etiología , Trombosis/epidemiología , Trombosis/etiología , Trombosis/prevención & controlAsunto(s)
Amplificación de Genes , Reordenamiento Génico , Leucemia Promielocítica Aguda/genética , Proteínas de Fusión Oncogénica/genética , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 17 , Sondas de ADN , Humanos , Leucemia Promielocítica Aguda/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Translocación GenéticaRESUMEN
The JAK2(V617F) mutation occurs in 50% of patients with essential thrombocythemia (ET). We investigated the correlation between the JAK2(V617F) mutation and clinical and laboratory characteristics, thrombohemorrhagic risk and incidence of disease evolution in 275 patients with ET followed for a median follow-up of 7 years. JAK2(V617F) mutation was detected in 175 patients (64%), of whom 173 were heterozygous. Patients with the mutation were older and displayed higher hemoglobin and hematocrit levels, but lower platelet count. Cytotoxic treatment requirement was similar in the two groups, but patients with the mutation showed better responses. Incidence of thrombosis and disease evolution was comparable. JAK2 mutational status assessment was valuable to distinguish two populations of patients with ET, showing distinctive hematologic and clinical features.