Valor de la expresión del ARN mensajero de la isocitrato deshidrogenasa (IDH1) como predictor de agresividad en gliomas

Los gliomas son el tipo más común de tumor cerebral primario. En humanos, cinco genes codifican para la isocitrato deshidrogenasa: IDH1/2/3A/3B/3G. Mutaciones somáticas puntuales en el gen IDH1 son frecuentes en gliomas, la mayoría transiciones de una sola base: 395G-A y están asociadas a una mayor supervivencia de esos pacientes con glioma cuando los comparamos con aquellos que no tienen la mutación. Entre las consecuencias funcionales de la mutación de la IDH1, estudios demuestran un fuerte descenso en la producción de NADPH reducido dependiente de isocitrato en las células. Investigamos la expresión del ARNm del IDH1 y la presencia o ausencia de la mutación G395A en una serie de gliomas. En particular, estudiamos 38 casos de gliomas y 7 metástasis analizando el centro y la periferia de muestras en fresco y resección en bloque. No encontramos diferencias entre las regiones central y periférica con respecto a la expresión del ARNm y la mutación de IDH1. Sin embargo, podemos observar una mayor expresión del ARNm de IDH1 y una menor incidencia de la mutación en tumores de alto grado cuando los comparamos con aquellos de bajo grado. Este estudio muestra que los gliomas con IDH1 normal tienen una mayor expresión de ARNm independientemente de la zona del tumor. Esto podría conducir a un aumento en la actividad enzimática y mayor presencia de NADPH, lo cual se necesita para el crecimiento celular. Así, el mayor poder de reducción de estas células podría explicar la mayor agresividad de estos gliomas.Gliomas, are the most common type of primary brain tumors. In humans, five genes encode for isocitrate dehydrogenase: IDH1, IDH2, IDH3A, IDH3B, and IDH3G. Somatic point mutations in IDH1 are frequent in gliomas. Most mutations for IDH1 are single base transition substitutions: 395G_A and are associated with longer survival in patients with glioma when compared with those gliomas without IDH1 mutations. Among the functional consequences of IDH1 mutation, some studies have shown a strong decrease in the isocitrate dependent production of reduced NADPH production in the cells. We investigated mRNA expression of IDH1 and the presence or absence of the G395A mutation in a subset of gliomas. Specifically, we studied 38 cases of glioma and 7 methastasis analyzing central and peripheral regions from fresh and en block resection specimens. We found no differences between central and peripheral regions, in regard to IDH1 mRNA expression and G395A IDH1 mutation. However, we identified a significantly higher expression of IDH1 mRNA and a lesser incidence of mutation in high grade gliomas when compared with low grade ones. This study shows that those gliomas with IDH1 WT are associated with higher expression of IDH1 mRNA, independently of the tumor area. This could in turn lead to an increase in enzyme activity and more presence of NADPH which is needed for cellular growth. The greater reducing power in these cells could account for the greater aggressiveness of these gliomas

Response to Novel Drugs before and after Allogeneic Stem Cell Transplantation in Patients with Relapsed Multiple Myeloma

Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P <.001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P <.001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment

La influencia de los padres sobre el consumo de alcohol y tabaco y otros hábitos de los adolescentes de Palma de Mallorca en 2003

Fundamento. El consumo de alcohol y tabaco es frecuente entre los adolescentes. El objetivo de este estudio fue determinar la influencia de los hábitos de los padres en los de sus hijos. Métodos. Se estudió a los adolescentes de 13 a 15 años de la isla de Mallorca y a sus padres. Mediante métodos previamente validados se recabó su nivel socioeconómico, sus hábitos (ingesta de alcohol, tabaquismo, práctica de deportes y consumo de televisión), y el rendimiento académico de los adolescentes. Resultados. Participaron 4.019 adolescentes y 7.359 padres. Un bajo nivel socioeconómico se asoció con un mayor riesgo de que los adolescentes fumaran (OR=3,86, IC 95%: 2,30-6,48; p=0,000), bebieran alcohol (OR=1,88; 95% IC: 1,40- 2,54; p=0,000), suspendieran alguna asignatura (OR=6,37, IC 95%: 4,23-9,61; p=0,000), vieran > 2 horas diarias de televisión (OR=1,97;95%IC: 1,69-2,29; p=0,000), y no practicaran deporte (OR=0,55, IC 95%: 0,38-0,80; p=0,001). Además, en el riesgo de que fumaran influyó que la madre bebiera (OR 1,76 IC95% 1,24-1,51; p=0,002), en el de que suspendieran los hijos (no las hijas) que los padres fumaran (OR 1,89 IC95% 1,33- 2,68; p=0,000), y los correspondientes hábitos en los padres aumentaron la probabilidad de que los adolescentes bebieran alcohol (OR 1,91 IC95% 1,43-2,51; p=0,000), vieran más de 2 horas diarias la televisión (OR 1,97 IC95% 1,68-2,29; p=0,000) e hicieran deporte (OR 6,67 IC95% 2,57-14,96; p=0,000). Conclusiones. Un bajo nivel socioeconómico se asocia a un mayor riesgo de que los adolescentes españoles fumen, beban alcohol, suspendan, vean más televisión y no practiquen deporte. Además, el que la madre beba se asocia a un mayor riesgo de que sus hijos fumen y beban, y el que ambos padres beban se asocia a un mayor riesgo de que sus hijos lo hagan. La práctica de deportes y el tiempo que pasan ante el televisor los padres influyen en los hábitos correspondientes por parte de sus hijos, pero no influyen en que el adolescente beba o fume

Complete response associated with lenalidomide and celecoxib in a case of primary refractory Hodgkin lymphoma

Marta Garcia-Recio,1,2 Jordi Martinez-Serra,1 Francesc Mestre,2,3 Leyre Bento,1,2 Jordi Gines,4 Rafael Ramos,2,5 Jaime Daumal,2,6 Paloma L&oacute;pez,2,3 Antonia Sampol,1 Antonio Gutierrez1,2 1Hematology Department, 2Lymphoma Unit, 3Radiotherapy Department, 4Pharmacy Department, 5Pathology Department, 6Nuclear Medicine Department, Son Espases University Hospital, IdISBa, Palma, Spain Abstract: Hodgkin lymphoma (HL) represents ~11% of all lymphoma cases. This disease occurs in young adults, but also affects people over 55 years of age. Despite the fact that &gt;80% of all newly diagnosed patients under 60 will achieve a sustained complete response (CR), 5%&ndash;10% of HL patients are refractory to initial treatment and 10%&ndash;30% of patients will eventually relapse after an initial CR. The treatment recommendation for primary refractory or relapsed HL patients is salvage therapy followed by high-dose chemotherapy and autologous stem cell transplantation. Following this approach, a significant part will still relapse at any moment. Thus, further research and new drugs or combinations are required. Overexpression of COX-2 has been associated with poor prognosis in relapse/refractory HL patients, so it could be a potential therapeutic target in HL. For this purpose, several drugs may have a role: specific COX-2 inhibitors such as celecoxib or other anti-inflammatory drugs such as lenalidomide may further inhibit lipopolysaccharide-mediated induction of COX-2. Moreover, lenalidomide and COX-2 inhibitors (celecoxib) have been tested in solid tumors with encouraging results. We present a case of a young female diagnosed with a heavily pretreated HL nodular sclerosis subtype who, after failing six treatment lines, only achieved clinical and radiological CR after six cycles of lenalidomide/celecoxib that resulted in an event-free survival of 22 months. We explain the rationale of using this chemotherapy regimen and our patient follow-up. Keywords: Hodgkin lymphoma, relapse, celecoxib, lenalidomide, COX-

Complete response associated with lenalidomide and celecoxib in a case of primary refractory Hodgkin lymphoma.

Abstract: Hodgkin lymphoma (HL) represents ~11% of all lymphoma cases. This disease occurs in young adults, but also affects people over 55 years of age. Despite the fact that >80% of all newly diagnosed patients under 60 will achieve a sustained complete response (CR), 5%-10% of HL patients are refractory to initial treatment and 10%-30% of patients will eventually relapse after an initial CR. The treatment recommendation for primary refractory or relapsed HL patients is salvage therapy followed by high-dose chemotherapy and autologous stem cell transplantation. Following this approach, a significant part will still relapse at any moment. Thus, further research and new drugs or combinations are required. Overexpression of COX-2 has been associated with poor prognosis in relapse/refractory HL patients, so it could be a potential therapeutic target in HL. For this purpose, several drugs may have a role: specific COX-2 inhibitors such as celecoxib or other anti-inflammatory drugs such as lenalidomide may further inhibit lipopolysaccharide-mediated induction of COX-2. Moreover, lenalidomide and COX-2 inhibitors (celecoxib) have been tested in solid tumors with encouraging results. We present a case of a young female diagnosed with a heavily pretreated HL nodular sclerosis subtype who, after failing six treatment lines, only achieved clinical and radiological CR after six cycles of lenalidomide/celecoxib that resulted in an event-free survival of 22 months. We explain the rationale of using this chemotherapy regimen and our patient follow-up