RESUMEN
Aplastic anemia (AA) is a rare, life-threatening hematological disease, with a poorly defined incidence. As the data available on AA varies substantially worldwide, a multicenter, ambispective, observational study was carried out between 2010 and 2019 to assess the incidence, clinical management and survival of AA at seven Spanish hospitals. The incidence of AA was 2.83 per million inhabitants per year, consistent with that reported previously in Europe, with a median age at diagnosis of 61 years-old (range 12-86), and a similar number of males and females. The initial diagnosis was severe or very severe AA in 55.8% of cases and 93.7% required transfusion. The most frequent first line therapy was anti-thymocyte globulin (ATG) plus cyclosporin A (CsA, 44.2%), followed by other CsA-based regimes (46.3%), with hematopoietic stem cell transplantation an infrequent 1st line therapy. The 6-month response rate was 68.2%, which then increased over a median follow-up of 3.9 years. The 5-year overall survival (5OS) was 73.6%, similar in severe (78.6%) and very severe AA patients (74.6%) but lower in moderate AA (MAA) patients (68.4%). The 5OS was 100% in 0-25 year-old patients but dropping to 58.3% in patients ≥ 60 years-old. At the last contact, 75.8% of the patients were alive. In conclusion, the incidence, characteristics and management of AA in our study are consistent with that reported previously. In terms of survival, although the global long-term OS rate was good, there is room for improvement, particularly in older patients. Finally, what appears to be a worse long-term survival of MAA patients, as reported previously, reinforces the importance of not underestimating this condition when diagnosed as MAA.
Asunto(s)
Anemia Aplásica , Trasplante de Células Madre Hematopoyéticas , Masculino , Femenino , Humanos , Anciano , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Recién Nacido , Lactante , Preescolar , Anemia Aplásica/terapia , Anemia Aplásica/tratamiento farmacológico , España/epidemiología , Incidencia , Suero Antilinfocítico/uso terapéutico , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Resultado del TratamientoRESUMEN
Bosutinib is a second-generation tyrosine kinase inhibitor (2GTKI) approved at 400 mg once daily (QD) as first-line therapy in patients with chronic myeloid leukemia (CML) patients and at 500 mg QD in patients who are resistant to or intolerant of prior therapy. In clinical practice, bosutinib is often given to patients who have failed imatinib, nilotinib, and dasatinib (i.e., as fourth-line treatment), despite the limited data on its clinical benefit in this setting. We have retrospectively evaluated the results of bosutinib in a series of 62 CML patients who have failed to prior treatment with all three, imatinib, nilotinib, and dasatinib. Median time on TKI treatment before bosutinib start was 105 (9-163) months, and median duration on bosutinib was 9 months (1-30). Overall, probabilities to achieve complete cytogenetic response (CCyR) and major molecular response (MMR) were 25% and 24% respectively. After a median follow-up period of 14 months, the event-free survival and progression-free survival were 68 and 85%, respectively. Sixty-four percent of patients in CCyR at the time of bosutinib start were able to achieve MMR. In contrast, patients without CCyR, probabilities to obtain CCyR and MMR were 25% and 14%. Bosutinib was well tolerated in this heavily pretreated patients' cohort. Pleural effusions and diarrhea were the most frequent grade II-IV side effects, leading to treatment discontinuation in 16% of patients. Bosutinib is an effective treatment option for patients who have failed previous 2GTKIs due to intolerance. However, efficacy seems to be related to the molecular response that the patient achieved prior to bosutinib.
Asunto(s)
Compuestos de Anilina/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Nitrilos/administración & dosificación , Quinolinas/administración & dosificación , Adulto , Compuestos de Anilina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Nitrilos/efectos adversos , Quinolinas/efectos adversos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Studies comparing rabbit antithymocyte globulin (rATG) and horse ATG (hATG) in patients with aplastic anemia (AA) have shown conflicting results. These studies included fewer than 60 subjects in the rATG arm with relatively short follow-up. A total of 169 patients treated with rATG and 62 treated with hATG were included in this retrospective analysis, across 33 centers. Patients were treated with rATG or hATG plus cyclosporine A. Over half were classified, as having severe AA (SAA) or very severe AA (VSAA), and the mean follow-up was 45 months. There was no significant difference detected in cumulative response to treatment or survival between the rATG and hATG groups. The response to treatment was 63 % in the rATG group versus 66 % in the hATG group at 3 months. By 12 months, this pattern had reversed, and 84 % of rATG patients had responded to treatment versus 76 % in the hATG group (n.s.). Early mortality due to infection tended to be higher with rATG compared to hATG (n.s). rATG and hATG would seem to be therapeutically equivalent in SAA and VSAA. However, patients treated with rATG may take longer to respond than those treated with hATG and may also require more active prevention of early infections.
Asunto(s)
Anemia Aplásica/sangre , Anemia Aplásica/tratamiento farmacológico , Suero Antilinfocítico/administración & dosificación , Adulto , Anciano , Anemia Aplásica/diagnóstico , Animales , Femenino , Estudios de Seguimiento , Caballos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Conejos , Estudios Retrospectivos , Especificidad de la Especie , Resultado del Tratamiento , Adulto JovenRESUMEN
(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3-4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs.
RESUMEN
Carotid atherosclerotic plaque remodelling and increased risk of symptomatic plaque rupture seem to be partially mediated by matrix metalloproteinases (MMPs). In this study, we have investigated whether different MMPs are related to carotid atherosclerosis or to recent ischaemic brain disease. Eighty-four consecutive patients undergoing carotid endarterectomy for symptomatic and asymptomatic disease were studied. Plaques were analysed by ultrasound and later by morphology. Plasma MMP-2, MMP-8 and MMP-9 levels were quantified by ELISA. MMP expression and activity in carotid plaques was analysed by Western blotting and in situ zymography. Results were analysed with respect to plaque stability, morphology, symptomatic disease, presence of vascular risk factors and plasma markers of acute inflammation as high sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer and white blood cell counts. Patients with hypoechogenic plaques on ultrasound had more plasma MMP-8 (p = 0.04) and increased MMP activity as assessed by in situ zymography. Asymptomatic patients with plaque progression had more active intraplaque MMP-8 than asymptomatic patients without plaque progression. Presence of recent intraplaque haemorrhage or past history of CAD was related to increased activity of MMPs as assessed by in situ zymography (p < 0.01, CI 95% 0.8-1.0). Plasma MMP-8 and MMP-9, but not MMP-2 levels, decrease with time after ischaemic stroke. Patients with hypertension had more intraplaque active MMP-9 than normotensive (p = 0.03, CI 95% 0.7-1.0). Hypoechogenic carotid plaques had increased MMP activity and asymptomatic patients with plaque progression show increase intraplaque MMP-8 levels.
Asunto(s)
Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/enzimología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/enzimología , Regulación Enzimológica de la Expresión Génica , Metaloproteinasa 8 de la Matriz/biosíntesis , Anciano , Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/patología , Progresión de la Enfermedad , Femenino , Humanos , Isquemia/patología , Masculino , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/biosíntesis , Persona de Mediana Edad , UltrasonografíaAsunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Niacinamida/análogos & derivados , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Pirazoles/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
The aim of this study was to assess the incidence of cytomegalovirus (CMV) infection and disease in patients with hematologic malignancies treated with alemtuzumab. The outcome of CMV infection in hematologic patients treated with alemtuzumab in 19 hospitals throughout Spain was assessed retrospectively. Data were collected from the medical records of patients over a period of 6 months following initiation of alemtuzumab therapy. We studied 102 patients (89 with B-cell chronic lymphocytic leukemia and 13 with other lymphoproliferative diseases, with a median age of 63 years [range 29-81 years]). Alemtuzumab was administered for a mean of 11.2 (standard deviation: 13.8) weeks, with a median total dose of 423 mg (range: 59-1440 mg). Alemtuzumab as a single agent was administered in 92.2% of patients and was associated with chemotherapy in 7.8% of cases. Prophylactic antivirals included famcyclovir (47%), acyclovir (34%), valacyclovir (14%) and valgancyclovir (5%). CMV viremia testing was performed a mean of 6.3 times (range: 1-19). The incidence of CMV infection was 38.9% (46% in patients treated with steroids and 75% in patients receiving ≥1000 mg of alemtuzumab). Treatment of CMV infection included gancyclovir or valgancyclovir in 94% of cases. Viremia became negative after a median of 20 days (95% CI: 13.4-26.6). CMV disease occurred in five patients. The incidence of CMV infection in alemtuzumab-treated patients was 38.9%. The incidence increased in patients treated concomitantly with steroids and in those treated with high doses of alemtuzumab, although only eight patients received 1000 mg or more, systematic monitoring of CMV viremia and early treatment of infection resulted in a favorable outcome of CMV reactivation.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antineoplásicos/uso terapéutico , Antineoplásicos/uso terapéutico , Infecciones por Citomegalovirus/epidemiología , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Trastornos Linfoproliferativos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Alemtuzumab , Anticuerpos Monoclonales Humanizados , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/tratamiento farmacológico , ADN Viral/sangre , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Trastornos Linfoproliferativos/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Esteroides/uso terapéuticoRESUMEN
Introducción: la población de 60 años y más requiere atención especial dado por la fragilidad que la caracteriza, que compromete su desempeño en las actividades elementales de la vida diaria. Muchos de ellos necesitan atención en instituciones como el hogar de ancianos, donde se les prestan servicios multidisciplinarios. Objetivo: evaluar el nivel de satisfacción de usuarios y prestadores de servicios en relación con la atención recibida en un hogar de ancianos. Material y Métodos: se realizó un estudio descriptivo transversal en el hogar de ancianos General Peraza, municipio 10 de Octubre, durante 2013. La evaluación se realizó mediante la aplicación del "Formulario para satisfacción de usuarios en Hogares de Ancianos" a 40 ancianos internos y del "Formulario para satisfacción de prestadores en Hogares de Ancianos" a 30 trabajadores de la Institución, validados previamente.Resultados: las variables relacionadas con condiciones de vida en usuarios resultaron con menos de 70 por ciento de respuesta buena. La atención recibida por médicos y personal de enfermería fue evaluada de buena en 100 por ciento y 95 por ciento respectivamente. El 87.5 por ciento de los ancianos refirió necesidad de ingresar, y solo 42.5 por ciento se siente a gusto. Las variables relacionadas con la satisfacción de prestadores fueron evaluadas entre regular y mala. Conclusiones: la satisfacción de usuarios y prestadores en el hogar de ancianos de manera general fue baja, hubo un bajo nivel de complacencia por el servicio recibido, insatisfacción con las condiciones de trabajo, privacidad y atención a sus problemas personales(AU)
Introduction: elderly population requires special attention due to the fragility that characterizes these persons, compromising their performance in the most elemental activities of life. Many of them require attention in institutions like the elderly homes, places where are provide a multidisciplinary services to all of those who can´t stay in their own houses.Objective: to assess the satisfaction levels of users and assistants relating to the assistance received at the Elderly home. Material and Methods: a descriptive and transversal study was made at "General Peraza" Elderly Home in 10 de Octubre Municipality, with capacity to 135 persons, during year 2013. Users satisfaction evaluation was done using the "Users satisfaction in Elderly Home Test" previously validated. Results: related variables with users´ life condition had less than 70 percent of correct answers. Attention provided by physicians and nurses was evaluated as "Good" in a 100 percent and 95 percent respectively by the patients. 87, 5 percent of the elderly patients admitted referred the necessity to be admitted at the institution, and only 42, 5 percent feel good there. Related variables with assistants were evaluated between "Regular" and "Bad". Conclusions: satisfaction level among users and assistants at the institution were low, low level of willingness with the received services, working conditions, privacy and attention to their own personal problems were insufficient(AU)