Clinical relevance of minimal residual disease monitoring in mature B-cell disorders: role of qualitative and quantitative PCR-based strategies Monitorização e relevância clínica da doença residual mínima nas síndromes linfoproliferativas de células B-maduras

Although current treatments can induce clinically complete remissions in a high proportion of patients with mature B-cell disorders (MBCD), most of them actually relapse, because of the persistence of residual tumour cells which are undetectable using conventional diagnostic procedures. Qualitative polymerase-chain-reaction (PCR) based methods are increasingly used for minimal residual disease (MRD) detection, and provide useful prognostic information. In recent years these assays have been integrated by reliable quantitative PCR-approaches that are likely to further increase the prognostic impact of MRD analysis in MBCD. In this review current approaches for qualitative and quantitative detection of MRD in MBCD are summarised. In addition, the prognostic aspects of molecular monitoring in the autologous and allogeneic transplantation setting are summarised. The experience accumulated over the past decade shows that PCR analysis has a prognostic impact in most MBCD especially when treated with high-dose regimens. Major advantages coming from the introduction of molecular monitoring in clinical programs have been: i) a rapid evaluation of the anti-tumour activity of innovative treatments; and ii) an early identification of patients with a high-risk of disease recurrence.<br>Os tratamentos atuais induzem remissão clínica completa em uma alta percentagem de pacientes portadores de Síndromes linfoproliferativas de células B maduras (SLBM). No entanto, muitos destes pacientes recaem devido a persistência de células tumorais residuais que são indetectáveis pelos métodos de diagnóstico convencionais. Os métodos baseados na reação em cadeia da polimerase (PCR) qualitativos cada vez mais têm sido utilizados para a detecção da doença residual mínima (DRM) e propiciam informações úteis em relação ao prognóstico dos pacientes. Neste relato as condutas atuais em relação a DRM e o emprego dos métodos de PCR qualitativos e quantitativos são apresentadas e discutida a importância da monitorização da DRM para os transplantes autólogos e alogênicos de medula óssea. A experiência acumulada nas últimas décadas demonstra que as análises de PCR têm um impacto no prognóstico da maioria das SLBM, especialmente nos pacientes submetidos a programas com altas doses de quimioterapia. As principais vantagens da monitorização molecular são: rapidez na avaliação da atividade anti-tumoral dos novos tratamentos e identificação precoce dos pacientes que apresentem alto risco de recaída de moléstia

Testing the significance of connectivity networks: Comparison of different assessing procedures

Despite the well-established use of partial directed coherence (PDC) to estimate interactions between brain signals, the assessment of its statistical significance still remains controversial. Commonly used approaches are based on the generation of empirical distributions of the null case, implying a considerable computational time, which may become a serious limitation in practical applications. Recently, rigorous asymptotic distributions for PDC were proposed. The aim of this work is to compare the performances of the asymptotic statistics with those of an empirical approach, in terms of both accuracy and computational time. Methods: Indices of performance were derived for the two approaches by a simulation study implementing different ground-truth networks under different levels of signal-to-noise ratio and amount of data available for the estimate. The two approaches were then applied to the resting-state EEG data acquired in a group of minimally conscious state and vegetative state/unresponsive wakefulness syndrome patients. Results: The performances of the asymptotic statistics in simulations matched those obtained by the empirical approach, with a considerable reduction of the computational time. Results of the application to real data showed that the asymptotic statistics led to the extraction of connectivity-based indices able to discriminate patients in different disorders of consciousness conditions and to correlate significantly with clinical scales. Such results were similar to those obtained by the empirical assessment, but with a considerable time economy. Significance: Asymptotic statistics provide an approach to the assessment of PDC significance with comparable performances with respect to the previously used empirical approaches but with a substantial advantage in terms of computational time