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 problemática general de la Educación : análisis de la situación educativa en Vizcaya

Elaborar un informe que permita a las personas involucradas en el desarrollo de una política educativa propia, situarse en las coordenadas educativas mundiales, estatales, vascas y vizcaínas. Los sujetos en edad escolar existentes en todos los municipios de Vizcaya. Investigación descriptiva que consta de dos partes: una primera en la que se recoge la problemática general que se plantea en el campo educativo a nivel mundial, estatal y vasco, ofreciendo al final de esta parte unas líneas de acción para el ámbito del País Vasco y para el ámbito de los municipios. Y una segunda parte en la que se describe numéricamente la situación en cada uno de los municipios Vizcaínos, de la oferta y la demanda de puestos escolares, condiciones de habitabilidad de dichos puestos, grado de gratuidad de los mismos y un presupuesto aproximado de lo que habría costado la financiación total de la EGB en el curso 77-78. Estudios referidos a la totalidad o a parte del ámbito escolar en la provincia de Vizcaya y que afectan a los distintos niveles escolares. Ayuntamientos, Juzgados y Parroquias. Los datos facilitados por los propios centros. Análisis de frecuencias absolutas. Existe un número suficiente de puestos escolares para EGB entre centros estatales y privados. Existe deficiencia de puestos de FPI ya que a ella se dirigen la mayoría de los menores de 16 años que no desean hacer BUP. Son pocas las aulas destinadas a Educación Especial. Partiendo del mapa escolar realizado de los datos del censo escolar de los últimos años, e introduciendo como factores correctivos los hechos de la disminución de la natalidad, disminución de la inmigración, escolarización obligatoria hasta los 16 años y posible unificación del BUP y la FPI, habría que hacer una proyección de la población escolar en 1983 a fin de determinar el número de plazas a crear en estos 5 años.País VascoES

Perennial herbaceous legumes as live soil mulches and their effects on C, N and P of the microbial biomass Leguminosas herbáceas perenes como cobertura viva do solo e seu efeito no C, N e P da biomassa microbiana

The use of living mulch with legumes is increasing but the impact of this management technique on the soil microbial pool is not well known. In this work, the effect of different live mulches was evaluated in relation to the C, N and P pools of the microbial biomass, in a Typic Alfisol of Seropédica, RJ, Brazil. The field experiment was divided in two parts: the first, consisted of treatments set in a 2 x 2 x 4 factorial combination of the following factors: live mulch species (Arachis pintoi and Macroptilium atropurpureum), vegetation management after cutting (leaving residue as a mulch or residue remotion from the plots) and four soil depths. The second part had treatments set in a 4 x 2 x 2 factorial combination of the following factors: absence of live mulch, A. pintoi, Pueraria phaseoloides, and M. atropurpureum, P levels (0 and 88 kg ha-1) and vegetation management after cutting. Variation of microbial C was not observed in relation to soil depth. However, the amount of microbial P and N, water soluble C, available C, and mineralizable C decreased with soil depth. Among the tested legumes, Arachis pintoi promoted an increase of microbial C and available C content of the soil, when compared to the other legume species (Pueraria phaseoloides and Macroptilium atropurpureum). Keeping the shoot as a mulch promoted an increase on soil content of microbial C and N, total organic C and N, and organic C fractions, indicating the importance of this practice to improve soil fertility.<br>A adoção de práticas de cobertura do solo com leguminosas tem aumentado. Porém, o impacto desta prática sobre o compartimento microbiano ainda não é bem conhecido. Para avaliar o efeito de diferentes leguminosas, sobre o C, N e P da biomassa microbiana, coletaram-se amostras de Argissolo oriundas de um experimento sob condições de campo em Seropédica-RJ. O experimento foi subdividido em dois ensaios. No primeiro, os tratamentos corresponderam à combinação de três fatores: espécie de cobertura viva (Arachis pintoi e Macroptilium atropurpurem), manutenção em cobertura ou remoção dos resíduos após o corte e profundidade de coleta do solo. No segundo ensaio, os tratamentos corresponderam à combinação de três fatores: ausência de cobertura viva, A. pintoi, Pueraria phaseoloides e M. atropurpureum, doses de P (0 e 88 kg ha-1) e manejo dos resíduos da parte aérea das plantas. Não houve variação do C microbiano com a profundidade do solo. Porém, para o P e N microbianos, C orgânico do solo, C solúvel em água, disponível e mineralizável, o aumento da profundidade proporcionou diminuição destas características. As leguminosas usadas influenciaram de maneira diferenciada as variáveis analisadas. O A. pintoi promoveu elevação nos teores de C microbiano e disponível, comparativamente as demais espécies utilizadas (P. phaseoloides e M. atropurpureum). A manutenção dos resíduos das leguminosas após cada corte promoveu aumentos nos teores de C e N microbianos, C orgânico e N total e frações de C orgânico do solo enfatizando a importância de utilização desta prática para melhorar a fertilidade do solo

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