Donor CTLA-4 genotype influences clinical outcome after T cell-depleted allogeneic hematopoietic stem cell transplantation from HLA-identical sibling donors.

CTLA-4 (cytotoxic T-lymphocyte antigen-4) plays a pivotal role in inhibiting T cell activation through competitive interaction with B7 molecules and interruption of costimulatory signals mediated by CD28. Polymorphisms on the CTLA-4 gene have been previously associated with autoimmune diseases, predisposition to leukemic relapse, and with graft-versus-host disease (GVHD) or relapse after allogeneic transplant. As CTLA-4 is expressed on T-lymphocytes, the aim of this study was to determine whether the donor CTLA-4 CT60 genotype also influences clinical outcome even after T cell depletion with CD34-positive selection. We studied 136 patient-donor pairs. Overall survival (OS) was worse for those patients who received grafts from a donor with the CT60 AA genotype rather than from a donor with the AG or GG genotype (35.6% vs 49.4%; P = .043). This association was confirmed through multivariate analysis, which identified the donor CT60 genotype as an independent risk factor for OS (P = .008; hazard ratio [HR]: 2.24, 95% confidence interval [CI]: 1.23-4.08). The donor CT60 AA genotype was also associated with lower disease-free survival, this being related to an increased risk of relapse (P = .001; HR: 3.41, 95% CI: 1.67-6.96) and a trend toward higher transplant-related mortality. These associations were stronger when considering only patients in the early stage of disease. Our results suggest that graft-versus-leukemia (GVL) activity after T cell depletion is conditioned by the donor CTLA-4 genotype.

Tromboc@t Working Group recommendations for management in patients receiving direct oral anticoagulants. / Recomendaciones del Grupo Catalán de Trombosis (Tromboc@t Working Group) para el tratamiento de los pacientes que reciben anticoagulantes orales directos.

BACKGROUND AND OBJECTIVES: In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation. MATERIAL AND METHODS: A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence. RESULTS: As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs. CONCLUSIONS: Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs.

Recomendaciones del Grupo Catalán de Trombosis (Tromboc@t Working Group) para el tratamiento de los pacientes que reciben anticoagulantes orales directos / Tromboc@t Working Group recommendations for management in patients receiving direct oral anticoagulants

Antecedentes y objetivos: En los últimos años los anticoagulantes orales directos (ACOD) se han convertido en una alternativa a los antagonistas de la vitamina K (AVK) para la prevención del ictus y embolia sistémica en pacientes con fibrilación auricular no valvular (FANV), así como para la prevención y tratamiento de la trombosis venosa profunda. Los ensayos clínicos han demostrado la no inferioridad y la potencial superioridad en comparación con la warfarina, lo cual permite ampliar las opciones de anticoagulación. En nuestro medio, las Unidades de Tratamiento Anticoagulante (UTA) y los Centros de Atención Primaria (CAP) son los encargados de la educación, seguimiento, control de adherencia y del manejo en situaciones especiales de los pacientes anticoagulados. Estas consideraciones han motivado la preparación del presente documento de consenso, que tiene como objetivo establecer recomendaciones que incorporen los hallazgos de la investigación científica a la práctica clínica para mejorar la calidad asistencial en el ámbito de la anticoagulación. Material y métodos: Un grupo de expertos del Grupo Catalán de Trombosis (TROMBOC@T) ha revisado la bibliografía publicada entre 2007 y 2016 para poder establecer recomendaciones basadas en la evidencia clínica. Resultados: Como resultado del proyecto se han establecido un conjunto de recomendaciones de carácter práctico que facilitarán el tratamiento, educación, seguimiento y manejo en situaciones especiales de los pacientes anticoagulados con ACOD. Conclusiones: El aumento progresivo del uso de los ACOD requiere establecer y homogeneizar las directrices de actuación clínica en el paciente anticoagulado con estos antitrombóticos tanto en las UTA como en los CAP

Background and objectives: In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation. Material and methods: A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence. Results: As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs. Conclusions: Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs