RESUMO
BACKGROUND: The objective of this study was to evaluate the effect of sorafenib on the outcomes of patients with acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 144 patients with FLT3-ITD AML undergoing allo-HSCT between January 2012 and December 2015 were enrolled in this study. Depending on whether they were receiving sorafenib before transplantation or sorafenib maintenance after transplantation, patients were divided into 4 groups: patients receiving sorafenib before transplantation (group A; n = 36), patients receiving sorafenib after transplantation (group B; n = 32), patients receiving sorafenib both before and after transplantation (group C; n = 26), and patients receiving sorafenib neither before nor after transplantation (group D; n = 50). Outcomes were compared among these groups. RESULTS: The 3-year relapse rates were 22.2%, 18.8%, 15.8%, and 46.1% for groups A, B, C, and D, respectively (P = .006). The 3-year overall survival (OS) rates were 74.9%, 78.1%, 84.6%, and 50.9%, respectively (P = .023), and the 3-year leukemia-free survival (LFS) rates were 69.4%, 78.1%, 80.4%, and 34.8%, respectively (P < .001). The relapse rate was higher and the LFS was shorter in group D versus groups A, B, and C. The OS in group D was shorter than the OS in group C but was similar to the OS in groups A and B. A multivariate analysis revealed that sorafenib before transplantation, sorafenib maintenance after transplantation, and their combined application were protective factors for a lower relapse rate (hazard ratios [HRs], 0.436 [P = .048], 0.431 [P = .046], and 0.173 [P = .002], respectively) and longer LFS (HRs, 0.322 [P = .010], 0.343 [P = .014], and 0.187 [P = .001], respectively). CONCLUSIONS: Sorafenib before transplantation, sorafenib maintenance after transplantation, and their combined application all could improve the outcomes for patients with FLT3-ITD AML. Further study is needed to determine whether the use of sorafenib both before and after transplantation might be ideal. Cancer 2018;124:1954-63. © 2018 American Cancer Society.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Mutação com Ganho de Função , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Domínios Proteicos/genética , Inibidores de Proteínas Quinases/farmacologia , Indução de Remissão/métodos , Estudos Retrospectivos , Duplicações Segmentares Genômicas/genética , Sorafenibe/farmacologia , Taxa de Sobrevida , Sequências de Repetição em Tandem/genética , Transplante Homólogo , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidoresRESUMO
In autosomal dominant skin disorders, a superimposed mosaic involvement arranged in a linear or otherwise segmental pattern is sometimes noted. Molecular proof of such "type 2 segmental manifestation" has so far been provided in Hailey-Hailey disease and Cowden syndrome. A similar superimposed segmental involvement can be found in numerous common disorders with a polygenic background, such a psoriasis, lichen planus, or vitiligo. In polygenic diseases, however, we can never recognize with certainty a "type 1 segmental manifestation", which is why we should use more neutral terms in the form of "isolated" versus "superimposed" segmental involvement. In the near future, the new paradigm of superimposed segmental manifestation may hopefully help elucidate the molecular basis of both monogenic and polygenic skin disorders (AU)
En los trastornos cutáneos autosómicos dominantes a veces se aprecia un mosaicismo sobreimpuesto con una disposición en patrón lineal o segmentario. La prueba molecular de ese tipo de «manifestación segmentaria tipo 2» la han proporcionado la enfermedad de Hailey-Hailey y el síndrome de Cowden. En numerosos trastornos frecuentes con una herencia poligénica como la psoriasis, el liquen plano o el vitíligo, se puede encontrar una afectación segmentaria sobreimpuesta similar. Sin embargo, en las enfermedades poligénicas nunca podemos reconocer con certeza una «manifestación segmentaria tipo 1», por 10 que utilizamos términos más neutrales, como afectación segmentaria «aislada» frente a «sobreimpuesta». En un futuro próximo el nuevo paradigma de manifestación segmentaria sobreimpuesta ayudará, en el mejor de los casos, a esclarecer la base molecular de los trastornos cutáneos monogénicos y poligénicos (AU)