ABSTRACT
ABSTRACT Introduction: Allogeneic hematopoietic stem cell transplantation offers the opportunity for extended survival in patients with Hodgkin's and non-Hodgkin lymphomas who relapsed after, or were deemed ineligible for, autologous transplantation. This study reports the cumulative experience of a single center over the past 14 years aiming to define the impact of patient, disease, and transplant-related characteristics on outcomes. Methods: All patients with histologically confirmed diagnosis of Hodgkin's or non-Hodgkin lymphomas who received allogeneic transplantation from 2000 to 2014 were retrospectively studied. Results: Forty-one patients were reviewed: 10 (24%) had Hodgkin's and 31 (76%) had non-Hodgkin lymphomas. The median age was 50 years and 23 (56%) were male. The majority of patients (68%) had had a prior autologous transplantation. At the time of allogeneic transplantation, 18 (43%) patients were in complete and seven (17%) were in partial remission. Most (95%) patients received reduced-intensity conditioning, 49% received matched sibling donor grafts, 24% matched-unrelated donor grafts, and 27% received double umbilical cord blood grafts. The 100-day treatment-related mortality rate was 12%. After a median duration of follow up of 17.1 months, the median progression-free and overall survival was 40.5 and 95.8 months, respectively. On multivariate analysis, patients who had active disease at the time of transplant had inferior survival. Conclusions: Allogeneic transplantation results extend survival in selected patients with relapsed/refractory Hodgkin's and non-Hodgkin lymphomas with low treatment-related mortality. Patients who have active disease at the time of allogeneic transplantation have poor outcomes.
Subject(s)
Transplantation, Homologous , Lymphoma, Non-Hodgkin , Hodgkin Disease , Hematopoietic Stem Cell TransplantationABSTRACT
La leflunomida, es un nuevo medicamento con eficacia comprobada en artritis reumatoide, derivada del isoxazol que no guarda relación estructural con otros fármacos inmunomoduladores. La leflunomida se metaboliza rápidamente a su forma activa, el A77 1726. Se han identificado dos mecanismos de acción para el A77 1726: inhibición de la dihidroorotato deshidrogenasa (DHODH) e inhibición de la tirosina quinasa. La inhibición de la DHODH se produce a concentraciones más bajas de A77 1726 que las de la tirosina quinasa y en la actualidad se considera que es el principal modo de acción. Los leucocitos estimulados han de incrementar los niveles de ribonucleótidos entre 8 y 16 veces antes de pasar de la fase G a la fase S. El aumento de los niveles de ribonucleótidos sólo puede conseguirse mediante síntesis de novo de estas moléculas. Con niveles bajos de ribonucleótidos, la p.53, una molécula "sensora", se activa e impide el avance del ciclo celular. En consecuencia, sería predecible que un inhibidor de la síntesis de novo de la uridina monofosfato detuviese las células estimuladas en la fase G. En apoyo de este mecanismo de acción, los linfocitos humanos de la sangre periférica estimulados con un mitógeno in vitro y tratados con A77 1726 sufren una detención en la fase G esta inhibición es revertida por la uridina