RESUMEN
PURPOSE: Prognostic Immunophenotyping in Myeloma Response (PRIMeR) is an ancillary study of minimal residual disease (MRD) assessment for multiple myeloma by next-generation multiparameter flow cytometry (MFC). Patients were enrolled on a three-arm randomized control trial (Blood and Marrow Transplants Clinical Trials Network 0702 Stem Cell Transplant for Myeloma in Combination of Novel Agents [STaMINA]; ClinicalTrials.gov identifier: NCT01109004). METHODS: Four hundred and thirty-five patients consented to the MRD panel, which included 10 monoclonal antibodies measured via six-color MFC. MRD was measured at baseline/preautologous hematopoietic cell transplant (BL/preAutoHCT), premaintenance (PM), and 1 year (Y1) after AutoHCT with a sensitivity of 10-5 to 10-6. The primary objective was to assess MRD-negative (MRDneg) at 1 year after AutoHCT and progression-free survival and overall survival (PFS/OS). RESULTS: Similar to the STaMINA results, at a median follow-up of 70 months, there was no significant difference in PFS/OS by treatment arm in the PRIMeR patients. MRDneg at all three time points was associated with significantly improved PFS, and MRDneg at Y1 had significantly longer OS. Multivariate analysis of PFS, adjusting for disease risk and treatment arm, demonstrated hazard ratios (HRs) in MRD-positive patients compared with MRDneg patients at BL, PM, and Y1 of 1.55 (P = .0074), 1.83 (P = .0007), and 3.61 (P < .0001), respectively. Corresponding HRs for OS were 1.19 (P = .48), 0.88 (P = .68), and 3.36 (P < .001). Patients with sustained MRDneg or who converted to MRDneg by Y1 had similar PFS/OS. CONCLUSION: To our knowledge, this first, prospective US cooperative group, multicenter study demonstrates that MRDneg at Y1 after AutoHCT with lenalidomide maintenance is prognostic for improved 6-year PFS and OS. Serial MRD measurements may direct trials to test how further therapy may improve long-term PFS and OS.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Lenalidomida , Mieloma Múltiple , Neoplasia Residual , Trasplante Autólogo , Humanos , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Adulto , Quimioterapia de Mantención , Citometría de Flujo , Supervivencia sin ProgresiónRESUMEN
O ruído ambiental tem sido implicado como um possível agente etiológico na hipertensäo arterial sistêmica. Face a importância deste aspecto ecológico, revisamos a literatura quanto aos efeitos agudos e crônicos da exposiçäo ao estresse sonoro sobre o aparelho cardiovascular, bem como os prováveis mecanismos fisisológicos capazes de participar na gênese destas alteraçöes. Discute-se a associaçäo entre a exposiçäo ao ruído e os aspectos epidemiológicos referentes a este problema, assim como a necessidade de adoçäo de medidas sanitárias capazes de permitir um melhor equacionamento do problema
Asunto(s)
Humanos , Hipertensión/etiología , Ruido/efectos adversos , Estrés Fisiológico/complicacionesRESUMEN
Simulaçöes säo um instrumento didático valioso para o treinamento da tomada de decisöes clínicas, aspecto fundamental na formaçäo médica. O uso do computador pode tornar esse método mais ágil e eficiente. É nosso objetivo implementá-lo nas disciplinas do departamento de Medicina Interna da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul. Com o auxílio de um microcomputador, dezessete simulaçöes clínicas estäo sendo experimentalmente aplicadas em uma turma do sexto semestre cursando a disciplina de Medicina Interna. A experiência inicial näo permite uma avaliaçäo da efetividade do método