[Anticoagulation and atrial fibrillation]. / Terapia anticoagulante en fibrilación auricular.

Atrial fibrillation is the most frequent cardiac arrhythmia in adults. Its frequency increases with age, being its incidence 1.5% in individuals 50 to 59 years old and 8-10% from 80 to 89 years. Atrial fibrillation increases 5 fold the risk of suffering stroke and actually causes 15% of all strokes. Its management focuses primary in the prevention of thromboembolic phenomena, heart rate and rhythm control. Anticoagulation, when indicated, has demonstrated to be the main tool in the prevention of these thromboembolic events. Although the bleeding complication is frequent in this population and increases with age, anticoagulation benefits are greater than the risks of bleeding. Due to the clinically heterogeneous nature of this arrythmia and the difficulty of establishing appropriate treatment for each particular case, the American College of Cardiology, the American Heart Association, European Society of Cardiology and American College of Chest Physicians have established guidelines to improve the management of these patients. The review of this condition and the proposed directives can notably facilitate and improve the management of the patients with atrial fibrillation.

Terapia anticoagulante en fibrilación auricular / Anticoagulation and atrial fibrillation

La fibrilación auricular es la taquiarritmia cardíaca más frecuente. Su incidencia aumenta con la edad, presentándose en un 1.5% entre los 50 a 59 años, y en un 8-10% entre los 80 a 89 años. Esta arritmia incrementa en cinco veces el riesgo de sufrir un evento cerebrovascular isquémico cardioembólico y causa el 15% de todos los accidentes cerebrovasculares isquémicos. Su manejo se enfoca en la prevención de los fenómenos tromboembólicos y el control de la frecuencia y ritmo cardíaco. El tratamiento anticoagulante ha demostrado ser la principal herramienta en la prevención de eventos cardioembólicos. Aunque las complicaciones hemorrágicas por el tratamiento son esperables y aumentan con la edad, el beneficio de usar anticoagulación sobrepasa por mucho al riesgo de sangrado. Precisamente debido a la heterogeneidad clínica de esta arritmia y a la dificultad de establecer un tratamiento adecuado para cada caso en particular, el American College of Cardiology, la American Heart Association, la European Society of Cardiology y el American College of Chest Physicians han establecido guías para mejorar el tratamiento de estos pacientes. La revisión de esta enfermedad y de las directrices propuestas puede facilitar y mejorar notablemente el tratamiento de los pacientes con fibrilación auricular.

Atrial fibrillation is the most frequent cardiac arrhythmia in adults. Its frequency increases with age, being its incidence 1.5% in individuals 50 to 59 years old and 8-10% from 80 to 89 years. Atrial fibrillation increases 5 fold the risk of suffering stroke and actually causes 15% of all strokes. Its management focuses primary in the prevention of thromboembolic phenomena, heart rate and rhythm control. Anticoagulation, when indicated, has demonstrated to be the main tool in the prevention of these thromboembolic events. Although the bleeding complication is frequent in this population and increases with age, anticoagulation benefits are greater than the risks of bleeding. Due to the clinically heterogeneous nature of this arrythmia and the difficulty of establishing appropriate treatment for each particular case, the American College of Cardiology, the American Heart Association, European Society of Cardiology and American College of Chest Physicians have established guidelines to improve the management of these patients. The review of this condition and the proposed directives can notably facilitate and improve the management of the patients with atrial fibrillation.

Hematopoietic stem cell transplantation in the era of tyrosine kinase inhibitors.

Until the 1990 s, the treatment of chronic myeloid leukemia (CML) recognized hematopoietic stem cell transplantation as the best treatment for those patients with an available donor. With the advent of imatinib in 2001, this paradigm changed dramatically as this drug provided outstanding and durable rates of hematologic, cytogenetic, and molecular responses. As a consequence it became the gold standard first-line treatment for most patients. However, after almost a decade of its use, it is clear that although very effective, imatinib cannot cure CML as transplantation has already proven so. Furthermore, the new non-myeloablative regimens and the improvements in survival after allogeneic transplant, especially in the field of unrelated transplants, offer this option to a broader population of patients with CML. This adds to the old question of whom to transplant, when and how to proceed with the allograft. This article reviews the current role of transplantation in the era of tyrosine kinase inhibitors and will try to elucidate its role in the frontline setting as well as after first- and second-line kinase inhibitors failure.

Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial.

PURPOSE Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population. PATIENTS AND METHODS Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%). CONCLUSION Dasatinib is effective in patients with CML-AP after imatinib treatment failure.

Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase.

Treatment options are limited for patients with imatinib-resistant or -intolerant accelerated phase chronic myeloid leukemia (CML-AP). Dasatinib is a novel, potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC-family kinases that showed marked efficacy in a phase 1 trial of patients with imatinib-resistant CML. Results are presented for 107 patients with CML-AP with imatinib-resistance or -intolerance from a phase 2, open-label study further evaluating dasatinib efficacy and safety. At 8 months' minimum follow-up, 81%, 64%, and 39% of patients achieved overall, major (MaHR), and complete hematologic responses, respectively, whereas 33% and 24% attained major and complete cytogenetic remission. Of 69 patients who achieved MaHR, 7 progressed. Seventy-six percent of patients are estimated to be alive and progression-free at 10 months. Response rates for the 60% of patients with baseline BCR-ABL mutations did not differ from the total population. Dasatinib was well tolerated: most nonhematologic adverse events (AEs) were mild to moderate; no imatinib-intolerant patients discontinued dasatinib because of AEs. Although common (76% of patients with severe neutropenia), cytopenias were manageable through dose modification. In summary, dasatinib induced significant hematologic and cytogenetic responses in patients with imatinib resistance or intolerance, was well tolerated, and may represent a potent new therapeutic option for CML-AP. Further follow-up is warranted. This trial was registered at www.clinicaltrials.gov as #CA180005.

Higher oxidation and lower antioxidant levels in peripheral blood plasma and bone marrow plasma from advanced cancer patients.

BACKGROUND: Bone marrow (BM) is an important tissue in the generation of immunocompetent and peripheral blood cells. The precursors of hematopoietic cells in BM undergo continuous proliferation and differentiation and are highly vulnerable to acute and chronic oxidative stress. Little is known about the oxidant and antioxidant status in the BM of untreated patients with nonhematologic tumors. In this study, oxidative stress was evaluated in peripheral blood plasma (PBP) and BM plasma (BMP) from lung carcinoma (LC) and breast carcinoma (BC) patients. METHODS: The sample included 13 consecutive untreated LC patients, 15 BC patients, and 11 healthy controls. Luminol-dependent chemiluminescence was used to evaluate oxygen radical generation by peripheral blood neutrophils. Lipid oxidation, assessed by 2-thiobarbituric acid-reactive substances (TBARS), and alpha-tocopherol, beta-carotene, and total ubiquinol-10 levels were determined in PBP and BMP. RESULTS: In LC and BC patients, neutrophil chemiluminescence was higher (128% and 264%, respectively) than in controls (P < 0.05). In cancer patients, TBARS levels were higher in both PBP (51% and 243% for LC and BC patients, respectively) and BMP (66% and 305% for LC and BC patients, respectively) than in plasma from controls (P < 0.01). alpha-Tocopherol and total ubiquinol-10 levels were significantly lower in BMP from BC patients compared with controls. In BC patients, alpha-tocopherol content in PBP was significantly lower than in controls. CONCLUSIONS: Untreated cancer patients presented an imbalance between oxidant generation and lipid-soluble antioxidant levels in favor of the former.

Transplante de medula osea en anemia aplastica severa / Blood marrow transplantation for severe aplstic anamia

La anemia aplástica severa (AAS) es una grave enfermedad hematológica en que el transplante de médula ósea (TMO) es el tratamiento de elección en pacientes pediátricos y adultos jóvenes, siendo el número de transfusiones pre-TMO el factor más importnate para determinar la incidencia de rechazos de injerto. Veinte pacientes com AAS, en sua mayoría politransfundidos, fueron sometidos a TMO utilizando la asociación ciclofosfamida (CFM) + globulina antilinfocitaria (GAL) como régimen condicionante. Todos los pacientes evaluables tuvieron injerto funcionante ("engraftment") y no se observó rechazo de injerto en ninguno de ellos. Tres pacientes fallecieron, y los 17 restantes (85 por ciento) están vivos y con reconstitución hematopoyética completa, con una mediana de seguimiento de 27.7 meses. EL TMO demostró ser una excelente opción terapéutica en esta serie de pacientes con AAS, y el régimen condicionante fue adecuado para una adecuada mieloablación e inmunosupresión pré-TMO sin rechazos tempranos o tardíos del injerto.

Transplante de medula osea en anemia aplastica severa / Blood marrow transplantation for severe aplstic anamia

La anemia aplástica severa (AAS) es una grave enfermedad hematológica en que el transplante de médula ósea (TMO) es el tratamiento de elección en pacientes pediátricos y adultos jóvenes, siendo el número de transfusiones pre-TMO el factor más importnate para determinar la incidencia de rechazos de injerto. Veinte pacientes com AAS, en sua mayoría politransfundidos, fueron sometidos a TMO utilizando la asociación ciclofosfamida (CFM) + globulina antilinfocitaria (GAL) como régimen condicionante. Todos los pacientes evaluables tuvieron injerto funcionante ("engraftment") y no se observó rechazo de injerto en ninguno de ellos. Tres pacientes fallecieron, y los 17 restantes (85 por ciento) están vivos y con reconstitución hematopoyética completa, con una mediana de seguimiento de 27.7 meses. EL TMO demostró ser una excelente opción terapéutica en esta serie de pacientes con AAS, y el régimen condicionante fue adecuado para una adecuada mieloablación e inmunosupresión pré-TMO sin rechazos tempranos o tardíos del injerto. (AU)