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Background: The analysis of molecular haematopoietic chimerisms (HC) has become a well-established method to monitor the transplant evolution and to assess the risk of relapse after allogeneic stem cells transplantation (allo-STC). Different techniques and molecular markers are being used for chimerism surveillance after transplantation, including quantitative real-time PCR (qPCR) and the recently developed digital PCR (dPCR). This study aims to compare the sensitivity and accuracy of both methods to quantify HC and predict early relapse. Methodology: HC was evaluated using custom PCR systems for the specific detection of the Y-chromosome, null alleles and insertion-deletion polymorphisms. A total of 281 samples from 28 adult patients who underwent an allo-SCT were studied. Increasing mixed chimerism was detected prior to relapse in 100% of patients (18 relapses). Results: Compared with conventional qPCR amplification, dPCR predicted relapse with a median anticipation period of 63 days versus 45.5 days by qPCR. Overall, 56% of the relapses were predicted earlier with dPCR whereas 38% of the relapses where detected simultaneously using both techniques and only in 1 case, relapse was predicted earlier with qPCR. Conclusions: In conclusion, chimerism determination by dPCR constitutes a suitable technique for the follow-up of patients with haematological pathologies after allo-STC, showing greater sensitivity to predict an early relapse. [ABSTRACT FROM AUTHOR]

A new methodology named CALMANT (CC-cube Algorithms on Meshes and Tori) for mapping a kind of algorithms that we call CC-cube algorithm onto multicomputers with hypercube, mesh, or torus interconnection topology is proposed. This methodology is suitable when the initial problem can be expressed as a set of processes that communicate through a hypercube topology (a CC-cube algorithm). There are many important algorithms that fit into the CC-cube type. CALMANT is based on three different techniques: a) the standard embedding to assign the processes of the algorithm to the nodes of the mesh multicomputer; b) the communication pipelining technique to increase the level of communication parallelism inherent in the CC-cube algorithms; and c) optimal message-scheduling algorithms proposed in this work in order to avoid conflicts and minimizing in this way the communication time. Although CALMANT is proposed for multicomputers with different interconnection network topologies, this paper only focuses on the particular case of meshes. [ABSTRACT FROM AUTHOR]

The increasing identification of driver oncogenic alterations and progress of targeted therapies addresses the need of comprehensive alternatives to standard molecular methods. The translation into clinical practice of next-generation sequencing (NGS) panels is actually challenged by the compliance of high quality standards for clinical accreditation. Herein, we present the analytical and clinical feasibility study of a hybridization capture-based NGS panel (Action OncoKitDx) for the analysis of somatic mutations, copy number variants (CNVs), fusions, pharmacogenetic SNPs and Microsatellite Instability (MSI) determination in formalin-fixed paraffin-embedded (FFPE) tumor samples. A total of 64 samples were submitted to extensive analytical validation for the identification of previously known variants. An additional set of 166 tumor and patient-matched normal samples were sequenced to assess the clinical utility of the assay across different tumor types. The panel demonstrated good specificity, sensitivity, reproducibility, and repeatability for the identification of all biomarkers analyzed and the 5% limit of detection set was validated. Among the clinical cohorts, the assay revealed pathogenic genomic alterations in 97% of patient cases, and in 82.7%, at least one clinically relevant variant was detected. The validation of accuracy and robustness of this assay supports the Action OncoKitDx's utility in adult solid tumors. [ABSTRACT FROM AUTHOR]