2,876 research outputs found

    IMAGING TECHNIQUES USED IN MULTIPLE MYELOMA

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    Multiple myeloma (MM) is a plasma cell disorder, characterised by bone marrow infiltration with clonal plasma cells; production of monoclonal immunoglobulin (paraprotein); end-organ damage; lytic lesions in the bones; renal impairment; hypercalcaemia and anaemia. Skeleton evaluation in MM is necessary not only for staging purposes but also to detect serious complications such as fractures. Skeletal survey is an established rst-line investigation for this purpose. However, in recent years, new imaging techniques such as whole-body magnetic resonance imaging and 2- uoro-2-deoxy-D-glucose positron emission tomography computed tomography have been used widely. In this article, we review different imaging techniques used in MM and their impact on patient management. Key words: Imaging techniques, magnetic resonance imaging, multiple myeloma, osteolytic lesions, positron emission tomography/computed tomography, skeletal survey

    Imaging in myeloma with focus on advanced imaging techniques.

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    In recent years, there have been major advances in the imaging of myeloma with whole body MRI incorporating diffusion-weighted imaging, emerging as the most sensitive modality. Imaging is now a key component in the work-up of patients with a suspected diagnosis of myeloma. The International Myeloma Working Group now specifies that more than one focal lesion on MRI or lytic lesion on whole body low-dose CT or fludeoxyglucose (FDG) PET/CT fulfil the criteria for bone damage requiring therapy. The recent National Institute for Health and Care Excellence myeloma guidelines recommend imaging in all patients with suspected myeloma. In addition, there is emerging data supporting the use of functional imaging techniques (WB-DW MRI and FDG PET/CT) to predict outcome and evaluate response to therapy. This review summarises the imaging modalities used in myeloma, the latest guidelines relevant to imaging and future directions

    MR imaging of therapy-induced changes of bone marrow

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    MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment

    Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders

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    This is an open access paper.-- et al.The European Myeloma Network (EMN) organized two flow cytometry workshops. The first aimed to identify specific indications for flow cytometry in patients with monoclonal gammopathies, and consensus technical approaches through a questionnaire-based review of current practice in participating laboratories. The second aimed to resolve outstanding technical issues and develop a consensus approach to analysis of plasma cells. The primary clinical applications identified were: differential diagnosis of neoplastic plasma cell disorders from reactive plasmacytosis; identifying risk of progression in patients with MGUS and detecting minimal residual disease. A range of technical recommendations were identified, including: 1) CD38, CD138 and CD45 should all be included in at least one tube for plasma cell identification and enumeration. The primary gate should be based on CD38 vs. CD138 expression; 2) after treatment, clonality assessment is only likely to be informative when combined with immunophenotype to detect abnormal cells. Flow cytometry is suitable for demonstrating a stringent complete remission; 3) for detection of abnormal plasma cells, a minimal panel should include CD19 and CD56. A preferred panel would also include CD20, CD117, CD28 and CD27; 4) discrepancies between the percentage of plasma cells detected by flow cytometry and morphology are primarily related to sample quality and it is, therefore, important to determine that marrow elements are present in follow-up samples, particularly normal plasma cells in MRD negative cases.The meetings were sponsored by the European Myeloma.Peer Reviewe

    Radiomics and Artificial Intelligence for Outcome Prediction in Multiple Myeloma Patients

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    The significant clinical heterogeneity of Multiple Myeloma (MM) patients implies that a set of consolidated biomarkers is currently missing. Radiomics is an advanced, quantitative feature-based methodology for image analysis. We assess the feasibility of an AI-based approach for the automatic stratification of MM patients from CT data, and for the automatic identification of radiological biomarkers with a possible prognostic value. A retrospective analysis of n = 33 transplanted MM with focal lesion were performed via an open-source toolbox that extracted 109 radiomics features. The redundancy reduction was realized via correlation and principal component analysis. The highest sensitivity and critical success index (CSI) were obtained representing each patient, with 17 focal features selected via correlation with the 24 features describing the overall skeletal asset. The Mann\u2013 Whitney U-test showed that three among the 17 imaging descriptors passed the null hypothesis. This computational approach to the interpretation of radiomics features shows the potential for the stratification of relapsed and non-relapsed MM patients, and could represent a prognostic image-based procedure for determining the disease follow-up and therapy

    Next-Generation Sequencing for Clinical Management of Multiple Myeloma : Ready for Prime Time?

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    Personalized treatment is an attractive strategy that promises increased efficacy with reduced side effects in cancer. The feasibility of such an approach has been greatly boosted by next-generation sequencing (NGS) techniques, which can return detailed information on the genome and on the transcriptome of each patient's tumor, thus highlighting biomarkers of response or druggable targets that may differ from case to case. However, while the number of cancers sequenced is growing exponentially, much fewer cases are amenable to a molecularly-guided treatment outside of clinical trials to date. In multiple myeloma, genomic analysis shows a variety of gene mutations, aneuploidies, segmental copy-number changes, translocations that are extremely heterogeneous, and more numerous than other hematological malignancies. Currently, in routine clinical practice we employ reduced FISH panels that only capture three high-risk features as part of the R-ISS. On the contrary, recent advances have suggested that extending genomic analysis to the full spectrum of recurrent mutations and structural abnormalities in multiple myeloma may have biological and clinical implications. Furthermore, increased efficacy of novel treatments can now produce deeper responses, and standard methods do not have enough sensitivity to stratify patients in complete biochemical remission. Consequently, NGS techniques have been developed to monitor the size of the clone to a sensitivity of up to a cell in a million after treatment. However, even these techniques are not within reach of standard laboratories. In this review we will recapitulate recent advances in multiple myeloma genomics, with special focus on the ones that may have immediate translational impact. We will analyze the benefits and pitfalls of NGS-based diagnostics, highlighting crucial aspects that will need to be taken into account before this can be implemented in most laboratories. We will make the point that a new era in myeloma diagnostics and minimal residual disease monitoring is close and conventional genetic testing will not be able to return the required information. This will mandate that even in routine practice NGS should soon be adopted owing to a higher informative potential with increasing clinical benefits

    Deep learning enables spatial mapping of the mosaic microenvironment of myeloma bone marrow trephine biopsies

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    Bone marrow trephine biopsy is crucial for the diagnosis of multiple myeloma. However, the complexity of bone marrow cellular, morphological, and spatial architecture preserved in trephine samples hinders comprehensive evaluation. To dissect the diverse cellular communities and mosaic tissue habitats, we developed a superpixel-inspired deep learning method (MoSaicNet) that adapts to complex tissue architectures and a cell imbalance aware deep learning pipeline (AwareNet) to enable accurate detection and classification of rare cell types in multiplex immunohistochemistry images. MoSaicNet and AwareNet achieved an area under the curve of >0.98 for tissue and cellular classification on separate test datasets. Application of MoSaicNet and AwareNet enabled investigation of bone heterogeneity and thickness as well as spatial histology analysis of bone marrow trephine samples from monoclonal gammopathies of undetermined significance (MGUS) and from paired newly diagnosed and post-treatment multiple myeloma. The most significant difference between MGUS and newly diagnosed multiple myeloma (NDMM) samples was not related to cell density but to spatial heterogeneity, with reduced spatial proximity of BLIMP1+ tumor cells to CD8+ cells in MGUS compared with NDMM samples. Following treatment of multiple myeloma patients, there was a reduction in the density of BLIMP1+ tumor cells, effector CD8+ T cells, and T regulatory cells, indicative of an altered immune microenvironment. Finally, bone heterogeneity decreased following treatment of MM patients. In summary, deep-learning based spatial mapping of bone marrow trephine biopsies can provide insights into the cellular topography of the myeloma marrow microenvironment and complement aspirate-based techniques

    CD229 (Ly9) a Novel Biomarker for B-Cell Malignancies and Multiple Myeloma

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    CD229 is a cell-surface molecule predominantly expressed on lymphocytes. Its expression in B-cell malignancies is poorly known. We tested the presence of this immunoreceptor on a large number of malignancies and normal tissue using a new monoclonal antibody and tissue microarrays. Our data show that CD229 expression is restricted to hematopoietic cells. It was strongly expressed in myeloma and marginal-zone lymphomas. Because of the high expression on multiple myeloma cells, we also analyze the presence of soluble CD229 in the sera of these patients. We showed that serum levels of soluble CD229 in myeloma patients, at the time of diagnosis, could be useful as a prognostic biomarker. Altogether, our results indicate that CD229 represents not only a useful disease biomarker but also an attractive therapeutic target. CD229 (Ly9) homophilic receptor, which belongs to the SLAM family of cell-surface molecules, is predominantly expressed on B and T cells. It acts as a signaling molecule, regulating lymphocyte homoeostasis and activation. Studies of CD229 function indicate that this receptor functions as a regulator of the development of marginal-zone B cells and other innate-like T and B lymphocytes. The expression on leukemias and lymphomas remains poorly understood due to the lack of CD229 monoclonal antibodies (mAb) for immunohistochemistry application (IHC). In this study, we used a new mAb against the cytoplasmic region of CD229 to study the expression of CD229 on normal tissues and B-cell malignancies, including multiple myeloma (MM), using tissue microarrays. We showed CD229 to be restricted to hematopoietic cells. It was strongly expressed in all cases of MM and in most marginal-zone lymphomas (MZL). Moderate CD229 expression was also found in chronic lymphocyte leukemia (CLL), follicular (FL), classic mantle-cell (MCL) and diffuse large B-cell lymphoma. Given the high expression on myeloma cells, we also analyzed for the presence of soluble CD229 in the sera of these patients. Serum levels of soluble CD229 (sCD229) at the time of diagnosis in MM patients could be useful as a prognostic biomarker. In conclusion, our results indicate that CD229 represents not only a useful biomarker but also an attractive therapeutic target
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